• Profound Fatigue

  • Potential Complication: Bedbound with development of pressure ulcers (prone to infection, malodor, and pain), and joint pain.
  • Family’s Possible Reaction/Concern: Patient is lazy and giving up.
  • Advice/Intervention:
    • Reassure family and caregivers that terminal fatigue will not respond to interventions and should not be resisted.
    • Use an air mattress if necessary.

  • Anorexia

  • Potential Complication: None specified as directly problematic.

  • Family’s Possible Reaction/Concern: Patient is giving up; patient will suffer from hunger and will starve to death.
  • Advice/Intervention:
    • Reassure family and caregivers that the patient is not eating because they are dying; not eating at the end of life does not cause suffering or death.
    • Forced feeding (oral, parenteral, or enteral) does not reduce symptoms or prolong life.

  • Dehydration

  • Potential Complication: Dry mucosal membranes.

  • Family’s Possible Reaction/Concern: Patient will suffer from thirst and die of dehydration.
  • Advice/Intervention:
    • Reassure family and caregivers that dehydration at the end of life does not cause sufferingbecause patients lose consciousness before any symptom distress.
    • Intravenous hydration can worsen symptoms of dyspnea (by pulmonary edema) and peripheral edema, and prolong the dying process.

  • Dysphagia (Inability to swallow oral medications)

  • Potential Complication: Inability to swallow oral medications needed for palliative care.

  • Family’s Possible Reaction/Concern: Not explicitly stated, but concern regarding medication administration is implied.
  • Advice/Intervention:
    • Do not force oral intake.
    • Discontinue unnecessary medications, including antibiotics, diuretics, antidepressants, and laxatives.
    • If swallowing pills is difficult, convert essential medications (analgesics, antiemetics, anxiolytics, and psychotropics) to oral solutions, buccal, sublingual, or rectal administration.

  • “Death Rattle” (Noisy breathing)

  • Potential Complication: Caused by secretions in the oropharynx.

  • Family’s Possible Reaction/Concern: Patient is choking and suffocating.
  • Advice/Intervention:
    • Reassure the family and caregivers that this is caused by secretions and the patient is not choking.
    • Reduce secretions with scopolamine (0.2–0.4 mg SC q4h or 1–3 patches q3d).
    • Reposition patient to permit drainage of secretions.
    • Do not suction; suction can cause patient and family discomfort and is usually ineffective.

  • Apnea, Cheyne-Stokes Respirations, Dyspnea

  • Potential Complication: Apneic episodes are frequently a premorbid change.

  • Family’s Possible Reaction/Concern: Patient is suffocating.
  • Advice/Intervention:
    • Reassure family and caregivers that unconscious patients do not experience suffocation or air hunger.
    • Opioids or anxiolytics may be used for dyspnea.
    • Oxygen is unlikely to relieve dyspneic symptoms and may prolong the dying process.

  • Urinary or Fecal Incontinence

  • Potential Complication: Skin breakdown if days until death. Potential transmission of infectious agents to caregivers.

  • Family’s Possible Reaction/Concern: Patient is dirty, malodorous, and physically repellent.
  • Advice/Intervention:
    • Remind family and caregivers to use universal precautions.
    • Frequent changes of bedclothes and bedding.
    • Use diapers, urinary catheter, or rectal tube if diarrhea or high urine output.

  • Agitation or Delirium

  • Potential Complication: Day/night reversal. Patient may hurt self or caregivers.

  • Family’s Possible Reaction/Concern: Patient is in horrible pain and going to have a horrible death.
  • Advice/Intervention:
    • Reassure family and caregivers that agitation and delirium do not necessarily connote physical pain.
    • Depending on the prognosis and goals of treatment, consider evaluating for causes of delirium and modifying medications.
    • Manage symptoms with haloperidol, chlorpromazine, diazepam, or midazolam.

  • Dry Mucosal Membranes (Cracked lips, mouth sores, candidiasis)

  • Potential Complication: Can cause pain. Odor. Patient may be malodorous, physically repellent.

  • Family’s Possible Reaction/Concern: Implied concern due to discomfort or appearance.
  • Advice/Intervention:
    • Use baking soda mouthwash or saliva preparation every 15–30 minutes.
    • Use topical nystatin for candidiasis.
    • Coat lips and nasal mucosa with petroleum jelly every 60–90 minutes.
    • Use ophthalmic lubricants every 4 hours or artificial tears every 30 minutes.

• Voluntary active euthanasia is defined as intentionally administering medications or other interventions to cause the patient’s death with the patient’s informed consent. Its legal status includes the Netherlands, Belgium, Luxembourg, Canada, Colombia, Spain, Western Australia, and New Zealand.

• Involuntary active euthanasia involves intentionally administering medications or other interventions to cause the patient’s death when the patient was competent to consent but did not (for example, the patient may not have been asked). This practice is not legally permitted anywhere.

• Passive euthanasia means withholding or withdrawing life-sustaining medical treatments from a patient to let the patient die (terminating life-sustaining treatments). This practice is legally permitted everywhere.

• Physician-assisted suicide occurs when a physician provides medications or other interventions to a patient with the understanding that the patient can use them to commit suicide. Its legal status includes the Netherlands, Belgium, Luxembourg, Canada, Colombia, Germany, Switzerland, Oregon, Washington, Montana, Vermont, California, Colorado, District of Columbia, Hawaii, Maine, New Jersey, and New Mexico.

• Neuroleptics:

  • Haloperidol:
    • Dose: 0.5–5 mg
    • Frequency/Route: q2–12h, PO/IV/SC/IM
  • Thioridazine:
    • Dose: 10–75 mg
    • Frequency/Route: q4–8h, PO
  • Chlorpromazine:
    • Dose: 12.5–50 mg
    • Frequency/Route: q4–12h, PO/IV/IM

  • Atypical Neuroleptics:

  • Olanzapine:

    • Dose: 2.5–5 mg
    • Frequency/Route: qd or bid, PO
  • Risperidone:
    • Dose: 1–3 mg
    • Frequency/Route: q12h, PO

  • Anxiolytics:

  • Lorazepam:

    • Dose: 0.5–2 mg
    • Frequency/Route: q1–4h, PO/IV/IM
  • Midazolam:
    • Dose: 1–5 mg/h
    • Frequency/Route: continuous infusion, IV/SC

  • Anesthetics:

  • Propofol:

    • Dose: 0.3–2.0 mg/h
    • Frequency/Route: continuous infusion, IV

I. Stimulant Laxatives

• Mechanism: Directly stimulate peristalsis and may reduce colonic absorption of water.
  • Prune juice
    • Dose: 120–240 mL/d
    • Comment: Works in 6–12 hours.
  • Senna (Senokot): Dose: 2–8 tablets PO bid
  • Bisacodyl: Dose: 5–15 mg/d PO, PR

II. Osmotic Laxatives

• Mechanism: These agents are not absorbed; they attract and retain water in the gastrointestinal tract.
  • Lactulose
    • Dose: 15–30 mL PO q4–8h
    • Comment: May cause flatulence and bloating; works in 1 day.
  • Magnesium hydroxide (Milk of Magnesia)
    • Dose: 15–30 mL/d PO
    • Comment: Works in 6 hours.
  • Magnesium citrate- Dose: 125–250 mL/d PO

III. Stool Softeners

• Mechanism: Increase water secretion and act as detergents, increasing water penetration into the stool.
  • Sodium docusate (Colace)
    • Dose: 300–600 mg/d PO
    • Comment: Works in 1–3 days.
  • Calcium docusate- Dose: 300–600 mg/d PO

IV. Suppositories and Enemas  Bisacodyl  Dose: 10–15 PR qd Sodium phosphate enema: Dose: Fixed dose, 4.5 oz Fleet’s PR qd

• Weak Opioids:

  • Purpose: For patients with mild dyspnea.
  • Codeine (or codeine with 325 mg acetaminophen):
    • Dose: 30 mg PO q4h.
    • Comments: Recommended for opioid-naïve patients.
  • Hydrocodone:
    • Dose: 5 mg PO q4h.

  • Strong Opioids:

  • Purpose: For opioid-naïve patients with moderate to severe dyspnea.

  • Morphine:
    • Dose: 5–10 mg PO q4h.
    • Comments: If patient is already taking opioids for pain/other symptoms, administer 30–50% of baseline opioid dose q4h.
  • Oxycodone:
    • Dose: 5–10 mg PO q4h.
  • Hydromorphone:
    • Dose: 1–2 mg PO q4h.

  • Anxiolytics:

  • General Administration: Give a dose every hour until the patient is relaxed; then provide a dose for maintenance.

  • Lorazepam:
    • Dose: 0.5–2.0 mg PO/SL/IV qh then q4–6h.
  • Clonazepam:
    • Dose: 0.25–2.0 mg PO q12h.
  • Midazolam:
    • Dose: 0.5 mg IV q15min.

Here are the steps in advance care planning:

• Introduce advance care planning
• Provide resources and recommend a proxy
• Have a structured discussion of scenarios with the patient
• Review the patient’s preferences
• Document the patient’s preferences
• Update the directive

The "P-SPIKES Approach" for communicating bad news involves the following steps and aims:

• P - Preparation: Mentally prepare for the interaction with the patient and/or family.

• S - Setting of the interaction: Ensure the appropriate setting for a serious and potentially emotionally charged discussion.

• P - Patient’s perception and preparation: Begin the discussion by establishing the baseline and whether the patient and family can grasp the information.

• I - Invitation and information needs: Discover what information needs the patient and/or family have and what limits they want regarding the bad information.

• K - Knowledge of the condition: Provide the bad news or other information to the patient and/or family sensitively.

• E - Empathy and exploration: Identify the cause of the emotions—e.g., poor prognosis—and empathize with the patient’s and/or family’s feelings.

• S - Summary and planning: Delineate for the patient and the family the next steps, including additional tests or interventions.

• Heart disease
• Malignant neoplasms (cancer)
• Accidents
• Chronic lower respiratory diseases
• Cerebrovascular diseases (stroke)
• Alzheimer’s disease
• Diabetes mellitus
• Nephritis, nephritic syndrome, nephrosis (kidney disease)
• Influenza and pneumonia
• Intentional self-harm (suicide)

MILD PAIN: Acetaminophen: 500 mg 2 tablets every 4-6 h Ibuprofen: 400 mg every 6 h; max 8 tablets per day (2400 mg/d qid)

MODERATE PAIN: Add to acetaminophen, NSAIDS Codeine: 30-60 mg every 4-8 h; maximum daily dose for pain 240 mg Tramadol: 25 mg PO every 6 h; max 400 mg/d Based on type of pain: NOCICEPTIVE PAIN: charecterized by: cramping, throbbing, aching, sharp, prickling, stabbing, deep and constant, dull and gnawing e.g., pancreatitis, bone metastases, tumor invasion, obstruction (of ureters, colon, gastric outlet, gallbladder, etc.) Treatment NSAIDs or acetaminophen with opioids NEUROPATHIC PAIN Charecterized by: burning, electrical, shock-like e.g., poststroke pain, tumor invasion of brachial plexus, herpetic neuralgia Treatment Gabapentin: 100-300 mg bid or tid, with 50-100% dose increments every 3 days; 3600 mg/d in 2 or 3 days

SEVERE PAIN: Add to acetaminophen, NSAIDs Morphine: 2.5-5 mg every 3-6 h orally Hydromorphone: 1-2 mg every 3-6 h orally Fentanyl transdermal: 1000-ug patch for 72 h Hydrocodone: 5-10 mg every 3-6 h orally

If pain still persists: Specialist Consultation (Consideration of surgical procedures such as nerve blocks)

Based on the 2003 Institute of Medicine (IOM) report, "Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care," effective communication is fundamentally linked to patient satisfaction, adherence to treatment, and health outcomes. The report highlights that a lack of effective communication is a key contributor to healthcare disparities.

Here's a breakdown of the link between effective communication and each of the outcomes:

• Patient Satisfaction: The report, along with related research, consistently links patient-provider race and ethnic concordance with higher patient satisfaction. Effective communication, including the use of professional interpreters and culturally competent care, addresses language and cultural barriers. When these barriers are overcome, patients feel more understood, respected, and involved in their care, leading to greater satisfaction. Research shows that minority patients, for example, report less partnership with physicians, which directly impacts their satisfaction with the care they receive.

• Adherence to Treatment: Effective communication is crucial for patients to understand their health condition, treatment plan, and why it is important to follow instructions. The report points out that a poor cultural match or misunderstanding of provider instructions can lead to poor comprehension and, consequently, lower adherence to treatment. This is particularly problematic for non-English speakers, where a lack of a professional interpreter can result in patients not fully understanding their care plan.

• Health Outcomes: The report establishes that the link between communication and outcomes is direct and significant. Ineffective communication contributes to racial and ethnic disparities in health outcomes, such as those seen in cardiovascular disease, diabetes, asthma, and cancer. The failure to communicate effectively can lead to:

  • Clinical Uncertainty: When a physician has difficulty understanding a patient's symptoms or background (e.g., due to language barriers or cultural differences), they may operate with greater uncertainty, potentially placing more weight on stereotypes or "priors" that can influence medical decisions and lead to suboptimal treatment.
  • Lower Quality of Care: When providers, organizations, and health systems do not prioritize culturally competent care, patients are at a higher risk of receiving lower-quality care, which can have negative health consequences.

In summary, the IOM report underscores that communication is not a soft skill but a critical component of high-quality care. A breakdown in communication due to cultural or linguistic barriers can lead to patient dissatisfaction, poor adherence to vital treatments, and ultimately, worse health outcomes, particularly for racial and ethnic minorities.

National Institute on Minority Health and Health Disparities (NIMHD) research framework identifies the following five domains of influence:

• Biological: This domain includes genetic factors, physiological function, and other biological mechanisms that influence health.
• Behavioral: This domain encompasses individual behaviors and coping strategies that affect health outcomes, such as diet, exercise, smoking, and substance use. The source also notes that it can include societal-level factors like policies and laws that are time-limited or modifiable.
• Physical/Built Environment: This domain refers to both the natural and man-made surroundings that impact health. It includes things like personal and household environments, community resources, and societal structures (e.g., the organization of government or justice systems).
• Sociocultural Environment: This domain includes social and cultural factors that shape health, such as sociodemographics, cultural identity, social networks, discrimination, and societal norms.
• Health Care System: This domain recognizes the healthcare system itself as a key determinant of health. It includes factors like health insurance coverage, health literacy, the patient-clinician relationship, and the availability and quality of health services.

Based on the works of Dr. G. D. Schiff and his colleagues, a diagnosis error is defined as any mistake or failure in the diagnostic process that results in one of three outcomes:

1. Misdiagnosis (or a wrong diagnosis): A patient is given an incorrect diagnosis, such as being told their chest pain is from acid reflux when it is actually a heart attack.
2. Missed diagnosis: A patient's true condition is never identified, and no definitive diagnosis is made.
3. Delayed diagnosis: The correct diagnosis is eventually made, but not in a timely manner. This delay may have led to a worse outcome for the patient because treatment was not started when it should have been.

Schiff's work, particularly from the multi-institutional collaborative project, highlights that these errors are not just a single, isolated event. Instead, they are the result of breakdowns that can occur at any of the many stages of the diagnostic process.

The key insights from his research include:

• Diagnosis as a System Property: The work emphasizes that diagnostic accuracy is a property of the entire healthcare system, not just the skill of an individual clinician. While individual cognitive mistakes can contribute, diagnostic errors often arise from systemic factors, such as faulty communication, lack of timely follow-up on test results, and administrative failures.

• A Multi-Stage Process: Schiff and colleagues break down the diagnostic process into several stages, including:

  • Access and patient presentation
  • History taking
  • The physical exam
  • Testing (ordering and interpreting)
  • Assessment and formulation of a differential diagnosis
  • Referral to specialists
  • Follow-up

  A failure at any one of these stages can lead to a diagnostic error. For example, a failure to follow up on an abnormal test result is a system error that can lead to a delayed diagnosis. * The Role of Hindsight: It is often difficult to definitively label a diagnostic error at the time it occurs. Errors are typically judged in hindsight, based on new information from subsequent tests, a specialist's opinion, or an autopsy.

In essence, Schiff and Leape's work moved the discussion of diagnostic errors away from simply blaming individual "bad doctors" and reframed it as a complex patient safety issue that requires system-wide solutions.

Based on the U.S. Surgeon General's Advisory on Building a Thriving Health Workforce, the solutions to health worker burnout are focused on a multi-faceted approach, emphasizing that addressing this crisis is a shared responsibility that requires change at the systemic, organizational, and individual levels.

The advisory outlines key actions for different stakeholders to create a culture of well-being and a more sustainable healthcare system. Here are the core solution themes:

1. Transforming Workplace Culture and Systems

• Prioritize Health and Safety: Organizations must build a commitment to health worker well-being into the very fabric of their operations. This includes providing adequate staffing, protecting workers from violence and harassment, and creating safe working conditions.
• Reduce Administrative Burdens: The advisory calls for a reduction in the time-consuming administrative tasks that take health workers away from patient care. Solutions include optimizing electronic health records (EHRs), streamlining documentation, and improving billing processes to be more efficient.
• Foster Team-Based Care and Social Connection: Building a sense of community and collaboration is crucial. Solutions involve implementing team-based models of care, encouraging peer support, and prioritizing opportunities for social connection to combat feelings of loneliness and isolation.
• Improve Autonomy and Work-Life Integration: Giving health workers a greater say in their schedules and processes can empower them and increase job satisfaction. Organizations should also offer flexible work arrangements, paid family and sick leave, and other family-friendly policies.

2. Removing Barriers to Mental Health and Well-being

• Eliminate Punitive Policies: A critical step is to remove the fear of professional consequences (such as losing a license) for seeking mental health or substance use care. This involves changing policies and addressing the stigma that prevents many health workers from getting help.
• Increase Access to Confidential Care: Organizations must provide easy, confidential access to high-quality mental health and substance use services, including on-demand counseling and after-hours care, to ensure health workers can get support when they need it.

3. Investing in a Diverse and Thriving Workforce

• Recruit and Retain a Diverse Workforce: Solutions include expanding the health workforce to meet demand and ensuring it is representative of the communities it serves. This helps address health inequities and workload issues.
• Promote Well-being in Training: Academic and training institutions must prioritize the well-being of students and trainees. This includes addressing the "hidden curriculum" of medicine that can lead to burnout, and promoting access to mental health resources early in a career.

In summary, the advisory positions health worker burnout as a "whole-of-society" problem, arguing that solving it is not just about individual coping mechanisms but about fundamental, collaborative changes to policies, technology, and culture across the entire healthcare system.

Based on the U.S. Surgeon General's Advisory on Health Worker Burnout, the factors associated with burnout among health workers are categorized into systemic, organizational issues rather than individual failings. The advisory and related documents highlight that burnout is an "occupational syndrome" driven by a range of factors that create a chronic imbalance between job demands and the resources available to meet them.

Here is a summary of the key factors that contribute to burnout, as outlined in the advisory:

System-Level Factors

These are the broader issues within the healthcare system and society that create a stressful environment.

• Excessive Workloads and Staffing Shortages: This is a major factor, where the demand for care outstrips the number of available health workers. This leads to longer hours, increased patient load, and less time for individual patient care and breaks.
• Administrative and Bureaucratic Burdens: Health workers spend a significant amount of time on tasks that are not directly related to patient care, such as documentation in electronic health records (EHRs), prior authorizations, and other administrative tasks. This time spent away from patients contributes to feelings of "moral distress" and decreases job satisfaction.
• Inequities and Discrimination: The advisory notes that factors like racism, bias, and discrimination in the workplace disproportionately affect the well-being of women and health workers of color, contributing to a higher risk of burnout.
• Workplace Violence and Harassment: Health workers face an increased risk of verbal and physical violence from patients, families, and even colleagues, which creates a psychologically and physically unsafe work environment.

Organizational and Cultural Factors

These are the issues within a specific workplace or institution that exacerbate stress.

• Lack of Control and Autonomy: Health workers often have limited input on their schedules, workflows, and how care is delivered. This lack of control can lead to feelings of powerlessness and a disconnect from their work.
• Weak Social Connection and Community: The advisory emphasizes that a lack of social support, peer-based care models, and a feeling of isolation within the workplace contributes to burnout.
• Punitive Policies for Seeking Mental Health Care: Many health professionals fear losing their licenses or facing professional stigma if they seek mental health or substance use care. This deters them from getting the help they need, which can worsen burnout and lead to more serious mental health issues.
• Misalignment of Values: Burnout can occur when a health worker's personal values and the mission of their organization don't align, or when the organization's culture doesn't support the values of teamwork, patient care, and well-being.
• Inefficient Technology: Poorly designed electronic health records and other health technologies can add to the administrative burden, increasing screen time and taking away from face-to-face patient interaction.

In short, the Surgeon General’s Advisory frames burnout not as a problem of individual resilience, but as a systemic issue rooted in the demanding and often flawed systems in which health workers operate. The solution, therefore, requires a comprehensive approach that targets these underlying systemic and organizational factors.

Physical clues for diagnosis:

• Amiodarone: Can cause blue pigmentation around the malar region.
• Myotonic dystrophy: Is characterized by a “hatchet face”, which results from temporal and facial muscle wasting. Other associated features include baldness in males and cataracts.
• Multiple endocrine neoplasia 2b (MEN2b): Is associated with mucosal neuromas on the lips and tongue, along with a marfanoid habitus.

• Parkinson’s gait is characterized by short, shuffling steps, forward flexion, an appearance of hurrying up (“festination”), hesitancy in turning, and absent arm swing, along with tremor.
• Sensory ataxia, caused by peripheral neuropathy or posterior column disease, manifests as a broad-based “stamping” gait, where the foot is struck down hard. This gait is worse at night when visual cues are diminished.
• Hemiplegic and diplegic or “spastic” gait both involve hypertonia in upper limb flexors and lower limb extensors and adductors, with ankles extended and toes pointed in, and circumduction with each step.
• Specifically, “scissor gait” is seen with diplegia (cerebral palsy).

• Eponymous nail changes (e.g., Beau’s line, Terry’s nails, Mee’s line, Muehrcke’s lines, half-and-half nails). While frequently seen, they are not diagnostically specific as they are associated with multiple conditions, including renal failure, liver failure, past or current severe illness, and hypoproteinemia.
• Koilonychia (spoon nails) is associated with iron deficiency anemia, though not exclusively.
• Nail pitting is seen in psoriasis and many other conditions.
• For cardiac conditions:
  • Splinter hemorrhages, Osler’s nodes, and Janeway lesions are found in endocarditis.
  • “Fingerization of the thumb” is a clue for Holt-Oram syndrome (especially with an atrial septal defect).
  • Arachnodactyly (long, slender fingers), the thumb sign, and the wrist sign are associated with Marfan syndrome.
• For Ehlers-Danlos syndrome, clues include joint hypermobility and lax, thin skin.
• For liver dysfunction: palmar erythema, spider angioma, and white nails can be observed.
• For endocrine conditions:
  • Moist, warm, tremulous extremities and onycholysis are seen in hyperthyroidism.
• For neurologic conditions:
  • Myotonic grip is associated with myotonic dystrophy.
  • Wrist drop indicates radial palsy.
  • Claw hand deformity is a sign of ulnar nerve palsy.
• For rheumatology:
  • Nail fold and capillary changes can be clues for vasculitis.
  • Heberden’s and Bouchard’s nodes are associated with osteoarthritis.
  • Swan neck deformity, subluxation, and ulnar deviation of fingers are seen in rheumatoid arthritis and other chronic inflammatory arthritis.
  • A telescoping hand can occur in destructive psoriatic or rheumatoid arthritis.
• For pulmonary conditions: nicotine staining on the fingers (often related to tobacco use) can be present.
• For congenital/developmental changes: A single transverse palmar crease is characteristic of Down’s syndrome.

• Odor of tobacco on clothing is noted as a general observation.
• A grapelike odor is associated with Pseudomonas wound infection.
• Fetid breath can be a clue for an anerobic lung abscess.
• A uriniferous odor is present in renal failure.
• An ammoniacal mousy odor indicates hepatic failure.
• An acetone-like fruity odor is characteristic of diabetic ketoacidosis.
• A fish odor is associated with trimethylaminuria.
• A bitter almond scent can be a sign of cyanide poisoning.
• The odor of alcohol metabolites is linked to intoxication or alcohol-induced delirium.

• Inappropriate clothing for the ambient weather can be a clue for hypothyroidism and hyperthyroidism.
• Neglect of clothing or color mismatch may indicate dementia or delirium.
• Untied shoelaces are associated with edema.
• A toe of a shoe cut out can be a sign of chronic gout. indicate dementia or delirium.

• Short stature can be a clue for growth hormone deficiency or Turner’s syndrome.
• Tall stature is associated with Marfan syndrome and individuals with a Marfanoid habitus.
  • Specific phenotypic features that strongly suggest Marfan syndrome include pectus carinatum, reduced elbow extension, a high-arched or “gothic” palate, an arm span–to–height ratio (ASHR) greater than 1.05, hindfoot deformity, downslanting palpebral fissures, the thumb sign, lens subluxation, myopia, dental crowding, joint laxity, and micrognation.

• Ottawa ankle rule

  • Condition Diagnosis: Ankle fracture
  • Clinical Scenario: Ankle injury

The Ottawa Ankle Rule is a clinical decision aid used to determine if a patient with an ankle injury requires an X-ray to check for a fracture. It is satisfied (meaning a negative result and no need for an X-ray) if the patient has none of the following:

Ankle X-ray is required if there is pain in the malleolar zone and any of the following:

• Bone tenderness along the distal 6 cm of the posterior edge of the tibia or the tip of the medial malleolus.

• Bone tenderness along the distal 6 cm of the posterior edge of the fibula or the tip of the lateral malleolus.

• Inability to bear weight both immediately after the injury and for four steps during the initial evaluation.

A foot X-ray is required if there is pain in the midfoot zone and any of the following:

• Bone tenderness at the base of the fifth metatarsal.

• Bone tenderness at the navicular bone.

• Inability to bear weight both immediately after the injury and for four steps during the initial evaluation.

The key takeaway, high diagnostic accuracy of a negative Ottawa ankle rule. When the rule is satisfied (meaning none of the criteria are met), the Likelihood Ratio is very low. This low LR means that the probability of an ankle fracture is dramatically reduced, allowing a clinician to confidently withhold an X-ray.

• Original Wells score

  • Condition Diagnosis: Deep venous thrombosis
  • Clinical Scenario: Acute calf pain and swelling
  • Definition: Clinicians combine a Wells score ≤0 with a negative quantitative D-dimer before stopping workup.

"Original Wells rule" for DVT:

Criteria for Deep Vein Thrombosis (DVT)

• Active cancer (ongoing treatment, or within the last 6 months, or palliative): +1 point

• Paralysis, paresis, or recent plaster immobilization of the lower limbs: +1 point

• Recently confined to bed for 3+ days or major surgery within the previous 12 weeks: +1 point

• Localized tenderness along the distribution of the deep venous system: +1 point

• Entire leg swelling: +1 point

• Calf swelling at least 3cm larger than the asymptomatic leg (measured 10cm below the tibial tuberosity): +1 point

• Pitting edema confined to the symptomatic leg: +1 point

• Collateral superficial veins (non-varicose veins): +1 point

• Previously documented DVT: +1 point

• Alternative diagnosis at least as likely as DVT: -2 points

The total score is then used to categorize the patient's risk of having a DVT:

• A score of 0 or less: Low probability for DVT.

• A score of 1 or 2: Moderate probability.

• A score of 3 or more: High probability.

• HINTS peripheral

  • Condition Diagnosis: Posterior circulation stroke
  • Clinical Scenario: Acute sustained vertigo, nausea, and vomiting

The term "HINTS peripheral" refers to the specific combination of findings on the HINTS exam that are consistent with a benign, peripheral cause of vertigo, such as vestibular neuritis or labyrinthitis. - Head Impulse Test (HI-): This test assesses the vestibulo-ocular reflex (VOR).

- **Peripheral finding:** The test is **abnormal** (or "positive"). This means that when the clinician rapidly turns the patient's head, the patient's eyes cannot stay fixed on the target (e.g., the clinician's nose) and must make a corrective "saccade" (a quick, jerky movement) to catch up. An abnormal Head Impulse Test is a reassuring sign because it indicates a problem with the peripheral vestibular system.

• Nystagmus (-N-): This test assesses for involuntary eye movements.

  • Peripheral finding: The nystagmus is unidirectional and horizontal. This means the eyes beat in one direction regardless of where the patient is looking. This is a reassuring sign. Conversely, nystagmus that changes direction with the gaze or is vertical is a sign of central pathology.

• Test of Skew (-TS): This test assesses for vertical eye misalignment.

  • Peripheral finding: The test is negative. There is no vertical misalignment of the eyes when the clinician quickly covers and uncovers them. This is a reassuring sign. The presence of a vertical correction ("skew deviation") is a sign of a central problem.

In summary, a "HINTS peripheral" finding means all three components of the HINTS exam are consistent with a peripheral cause: an abnormal Head Impulse Test, unidirectional nystagmus, and a negative Test of Skew. This is a powerful combination that allows a clinician to confidently "stop" the stroke workup and focus on managing the benign vestibular disorder.

• Alvarado score

  • Condition Diagnosis: Acute appendicitis
  • Clinical Scenario: Acute abdominal pain Alvarado score: often remembered by the mnemonic MANTRELS: for assessing likely hood of appendicitis.

• Migration of pain to the right iliac fossa (1 point)

• Anorexia (1 point)

• Nausea or vomiting (1 point)

• Tenderness in the right iliac fossa (2 points)

• Rebound tenderness (1 point)

• Elevated temperature (>37.3°C or 99.1°F) (1 point)

• Leukocytosis (>10,000/mm³) (2 points)

• Shift of leukocytes to the left (>70% neutrophils) (1 point)

A low Alvarado score (specifically, a score of 4 or less) has a very low Likelihood Ratio (LR = 0.1). This means that if a patient's symptoms, signs, and labs result in a score of 4 or less, the probability of them having acute appendicitis is dramatically decreased.

• Heckerling score

  • Condition Diagnosis: Pneumonia
  • Clinical Scenario: Acute cough and fever
  • Definition: The clinician scores 1 point for each of the following findings if present:
    • temperature >37.8°C
    • heart rate >100 beats/min
    • crackles
    • diminished breath sounds
    • absence of asthma.

score of 0 or 1 has a low likelyhood of pneumonia.

• Probe-to-bone test**

  • Condition Diagnosis: Osteomyelitis
  • Clinical Scenario: Diabetic foot ulcer
  • Definition: The clinician gently probes the foot ulcer with a blunt metal probe and identifies a rock-hard, gritty base without intervening soft tissue (positive test) or fails to observe this (negative test).

Negative test has low likelyhood of osteomyelitis.

It is a tool used in evidence-based medicine to help clinicians interpret the results of a physical exam.

It quantifies how a specific physical finding changes the probability of a particular disease being present.

Likelihood Ratio (LR)

The Likelihood Ratio is a statistical measure that tells you how much a test result (in this case, a physical sign) changes the odds of a patient having a disease.

LR = 1.0: The finding is useless. It does not change the probability of the disease at all.

LR > 1.0: The finding increases the probability of the disease. The higher the number, the more powerful the finding is for diagnosing the condition.

LR ≥ 10.0: A very strong indicator of the disease.

LR between 5.0 and 10.0: A strong indicator.

LR between 2.0 and 5.0: A weak indicator.

LR < 1.0: The finding decreases the probability of the disease. The lower the number (closer to 0), the more powerful the finding is for ruling out the condition.

LR ≤ 0.1: A very strong indicator for ruling out the disease.

LR between 0.1 and 0.5: A strong indicator for ruling out the disease.

LR between 0.5 and 1.0: A weak indicator for ruling out the disease.

The table is organized by diagnosis, and for each diagnosis, it lists various physical findings and their LRs.

"LIKELIHOOD RATIO IF FINDING IS: PRESENT": This column shows the LR when the finding is detected in a patient. A high number here (e.g., >2) is diagnostically helpful for confirming the disease.

"LIKELIHOOD RATIO IF FINDING IS: ABSENT": This column shows the LR when the finding is not detected. A low number here (e.g., <0.5) is diagnostically helpful for ruling out the disease.

"NS" (Not Significant): This abbreviation means the LR is close to 1.0, so the finding (whether present or absent) is not useful for the diagnosis.

Findings that have a high likelihood of "ruling in" and "ruling out" the diseases in question.

Findings with High Likelihood of "Ruling In" (High Positive Likelihood Ratio):

To "rule in" a disease, you look for findings with a high Likelihood Ratio (LR) when the finding is present. An LR of 5.0 or more is generally considered a strong indicator.

1. Elevated left heart filling pressures:

   • Positive abdominojugular test (LR = 8.0)
   • Displaced apical impulse (LR = 5.8)
   • Heart rate >100 beats/min (LR = 5.5)

2. Ascites:

   • Fluid wave (LR = 5.0)

3. Hepatopulmonary syndrome:

   • Cyanosis (LR = 4.4)
   • Clubbing (LR = 4.3)

4. Pneumonia:

   • Egophony (LR = 4.1)

Findings with High Likelihood of "Ruling Out" (Low Negative Likelihood Ratio):

To "rule out" a disease, you look for findings with a low Likelihood Ratio (LR) when the finding is absent. An LR of 0.3 or less is generally considered a strong indicator.

1. Ascites:

   • Edema is absent (LR = 0.2)
   • Flank dullness is absent (LR = 0.3)

2. Elevated left heart filling pressures:

   • Positive abdominojugular test is absent (LR = 0.3)

Findings that are not useful for the diagnosis of a disease are those with a Likelihood Ratio (LR) that is either not significant (NS) or falls between approximately 0.5 and 2.0 (as these values don't significantly change the probability of the disease).

1. Diagnosing Ascites in patients with abdominal distension: * The absence of shifting dullness (LR = 0.4) is near the cutoff but not a strong rule-out. The absence of a fluid wave (LR = 0.5) is also not strong enough to rule out ascites.

2. Diagnosing Hepatopulmonary Syndrome in patients with chronic liver disease: * The presence or absence of ascites (NS) is not useful. * The presence or absence of jaundice (NS) is not useful. * The absence of clubbing (LR = 0.6) and the absence of cyanosis (LR = 0.7) are not useful for ruling out the disease.

3. Diagnosing Pneumonia in patients with cough and fever: * The absence of percussion dullness (NS) is not useful. * The absence of egophony (NS) is not useful. * The absence of crackles (LR = 0.8) is not useful for ruling out the disease. * The absence of bronchial breath sounds (LR = 0.9) is not useful for ruling out the disease.

4. Diagnosing Elevated Left Heart Filling Pressures in patients with chest pain and dyspnea: * The absence of a heart rate >100 beats/min (NS) is not useful. * The presence or absence of crackles (NS) is not useful. * The absence of a displaced apical impulse (NS) is not useful. * The absence of an S3 gallop (LR = 0.8) is not useful for ruling out the disease.

Many physical signs, even if they seem clinically related to a disease, are not statistically powerful enough to be a reliable diagnostic tool, either for confirming a diagnosis or for ruling it out.

What is Pretest Probability?

The pretest probability is the likelihood or chance that a patient has a specific disease before any new diagnostic information (like a physical exam finding, lab test, or imaging study) is known. It's an estimate based on the patient's demographics, risk factors, and the overall prevalence of the condition in a similar group of patients.

How to Interpret the Table

The table provides pretest probabilities for a range of conditions in different clinical settings:

CLINICAL SETTING: This column describes the typical patient population where the diagnosis is being considered. For example, "Hospitalized with fever" or "Cough and fever."

DIAGNOSIS: This is the specific condition the clinician is trying to confirm or rule out.

PRETEST PROBABILITY (%): This column gives the estimated likelihood of the disease being present in that clinical setting.

MEDIAN: This is the middle value from the studies. It represents the most likely pretest probability.

RANGE: This shows the variation in probability found across different published studies. The range highlights that pretest probability isn't a fixed number; it can vary depending on the specific patient population.

Based on the provided table, here are the diseases that are highly associated with their presenting signs and symptoms, as indicated by a high median pretest probability:

• Osteomyelitis is highly associated with a diabetic foot ulcer. The median pretest probability is 65%, which is the highest in the table. This means that if a patient with diabetes has a foot ulcer, there's a very strong likelihood that the bone is also infected.

• Moderate-to-severe aortic regurgitation is highly associated with a murmur of aortic regurgitation. The median pretest probability is 42%. While not as high as osteomyelitis, this is still a substantial probability, indicating that the presence of the specific murmur makes the diagnosis of significant aortic regurgitation fairly likely.

The other conditions listed have lower pretest probabilities (in the 12% to 29% range), suggesting they are less strongly associated with their presenting signs and symptoms. For those conditions, the clinician would rely more heavily on additional diagnostic tests to confirm or rule out the diagnosis. The high probabilities for osteomyelitis and aortic regurgitation, however, mean that a clinician should be highly suspicious of these diagnoses from the very beginning.

• Dermatology:

  • Cellulitis
  • Psoriasis
  • Rosacea
  • Acne vulgaris
  • Eczema
  • Urticaria
  • Pityriasis rosea
  • Cutaneous lichen planus
  • Erythema multiforme
  • Hereditary hemorrhagic telangiectasia
  • Rubella
  • Measles
  • Herpes zoster
  • Erythema nodosum
  • Rationale:
    • Many dermatologic conditions are diagnosed by observation.
    • Skin biopsy is generally not needed for these examples unless there is diagnostic uncertainty.

  • Neurology:

  • Amyotrophic lateral sclerosis

  • Parkinson’s disease
  • Bell’s palsy
  • Peripheral neuropathy
  • Rationale:
    • Only the neurologic exam can determine the functional deficit of an abnormality found on CT or MRI.
    • Parkinson's disease is diagnosed by the presence of tremor, bradykinesia, rigidity, and the absence of atypical features.
    • Peripheral neuropathy is diagnosed by symptoms and signs, including decreased sensation, decreased or absent reflexes, and motor weakness.
    • Electromyography (EMG) and nerve conduction studies (NCS) are painful and should be ordered for specific reasons.
    • Sensory testing for pain and temperature (which involve small unmyelinated fibers) may be more sensitive than conventional NCS, which test larger myelinated nerve fibers.
    • Patterns of sensory loss help localization:
      • Glove and stocking pattern suggests peripheral neuropathy.
      • Radicular pattern suggests a root issue.
      • Brown-Sequard type pattern suggests a spinal cord issue.
      • “Crossed” signs (cranial nerve deficits on one side and motor deficit on the other) suggest brainstem lesions.

  • Rheumatology:

  • Rheumatoid arthritis

  • Lupus erythematosus
  • Scleroderma
  • Relapsing polychondritis
  • Patterns suggesting vasculitis (acute mononeuritis, palpable purpura)
  • Rationale:
    • The clinical exam is essential for both diagnosis and follow-up.
    • For conditions like rheumatoid arthritis or lupus, serology alone does not make the diagnosis.
    • A positive rheumatoid factor without other key clinical findings such as multiple joint involvement, constitutional symptoms, rheumatoid nodules, morning stiffness, or palpable synovitis is likely a falsely positive result.
    • Seronegative rheumatoid arthritis is a clinical diagnosis.

  • Cardiology:

  • Pericarditis

  • Rationale:
    • Diagnosis depends on combinations of characteristic chest pain, pericardial friction rub, and a characteristic electrocardiogram.
    • It's notable that 34–50% of cases have normal echocardiograms.

  • Ophthalmology:

  • Diabetic retinopathy

  • Conjunctivitis
  • Suspicion of keratitis
  • Iritis
  • Scleritis
  • Acute angle glaucoma
  • Retinal infarction
  • Rationale:
    • For "Red Eye" conditions, the internist must recognize symptoms and signs that require immediate ophthalmology referral. These include:
      • Peri-limbic erythema (ciliary flush)
      • Photophobia
      • Acute progressive pain
      • Vision loss
      • Foreign body sensation
      • Anisocoria
      • Fluid in the anterior chamber (hypopyon)
    • For Conjunctivitis:
      • The redness is most intense on the palpebral and peripheral bulbar conjunctiva.
      • Bacterial discharge is typically purulent, sticky, leading to eyes that are stuck shut and crusted.
      • Viral and allergic conjunctivitis can present with mucoid or watery discharge.
      • A history of hay fever, itching, and previous episodes suggests an allergic cause.

Likelihood Ratio (LR)

Is a statistical measure used in evidence-based medicine to assess how much a particular test result (in this case, a physical finding) changes the probability of a disease being present.

Here's a breakdown of the key points:

• The "Ruler" as a Diagnostic Aid: The "ruler" is a visualization tool designed for quick reference. It's divided into three sections based on the Likelihood Ratio (LR):

  • Right Side (LR $\geq$ 3.0): Findings in this section significantly increase the probability of heart failure. The higher the LR, the more powerful the finding is for diagnosing the condition.
  • Left Side (LR $\leq$ 0.3): Findings in this section significantly decrease the probability of heart failure. A very low LR means that the absence of a finding makes the disease much less likely.
  • Middle Section (LR between 0.3 and 3.0): Findings with LRs in this range are considered "diagnostically unhelpful." They don't significantly change the probability of the disease, so they are not included on the ruler. This is an important concept: just because a finding is present or absent doesn't mean it's clinically useful for diagnosis.

• Examples from the Text:

  • Presence of an S3 gallop (LR = 3.9): Since 3.9 is greater than 3.0, this finding is on the right side of the ruler. If a clinician hears an S3 gallop, the probability that the patient has heart failure significantly increases.
  • Presence of a displaced apical impulse (LR = 5.8): With an LR of 5.8, this is an even stronger finding than the S3 gallop. It is also on the right side of the ruler and powerfully increases the likelihood of heart failure.

• The Importance of "Absence" of a Finding: The text highlights a crucial distinction: the LR for the presence of a finding is often different from the LR for its absence.

  • The absence of an S3 gallop and the absence of a displaced apical impulse are mentioned, and their LRs fall between 0.3 and 3.0. This means that while finding them is very helpful for a diagnosis, not finding them is not particularly useful for ruling the disease out. A patient could still have heart failure even if these specific signs are absent.

In summary, the "ruler" is a practical, evidence-based tool that helps clinicians efficiently apply statistical probabilities to their physical exam findings. By focusing only on the findings with the highest and lowest likelihood ratios, it allows them to quickly and confidently identify which signs are most useful for diagnosing or ruling out heart failure, and which are simply not informative.

Chronic Care Model (CCM)

A widely recognized framework for redesigning healthcare systems to better manage chronic diseases. The explanation highlights two of its central tenets:

1. Patient-Centered and Engaged Care: This principle emphasizes that for care to be effective, patients with chronic conditions cannot be passive recipients of treatment. They must be active participants in their own health management. This involves a range of strategies to empower them, such as:

   • Patient education: Providing patients with clear information about their disease, medications, and self-management techniques.
   • Shared decision-making: Involving patients in discussions about their treatment options and respecting their preferences and values.
   • Goal setting: Collaborating with patients to set realistic and meaningful health goals.
   • Behavior change support: Offering tools and support to help patients adopt healthier lifestyles (e.g., diet, exercise, smoking cessation).

   The model recognizes that the patient is the most important member of the care team, and their engagement is crucial for long-term success in managing a chronic illness.

2. Team Care is Essential: This principle moves away from the traditional model where a single physician is responsible for all aspects of a patient's care. Instead, it advocates for a collaborative, interdisciplinary approach. A "team" might include:

   • Physicians
   • Nurses
   • Pharmacists
   • Dietitians
   • Social workers
   • Mental health professionals

   Each member of the team contributes their specific expertise to address the multifaceted needs of a patient with a chronic condition. For example, a dietitian might help a patient manage diabetes through diet, while a social worker might help them access community resources or navigate insurance issues. This coordinated effort ensures that all aspects of the patient's health are addressed, leading to more comprehensive and effective care.

In essence, the Chronic Care Model proposes that to achieve high-quality outcomes for people with chronic diseases, healthcare systems must move beyond episodic care and adopt a proactive approach that actively involves informed patients and a well-coordinated healthcare team. It's about building a system that supports both the patient and the providers in their shared goal of managing long-term health.

"Plan-Do-Check-Act" (PDCA) cycle

It is a continuous quality improvement model. It's a simple yet powerful framework used to implement changes and improve processes systematically.

Here's a breakdown of each stage:

• Plan: This is the initial, preparatory phase. The goal is to identify a problem or an opportunity for improvement and then develop a plan to address it. Key activities in this stage include:

  • Identifying the specific process to improve: What are you trying to fix or make better?
  • Defining the goals: What does "better" look like? What are the measurable outcomes you hope to achieve?
  • Identifying potential improvement strategies: Brainstorming and selecting a few ideas that you think might work. The text calls these "potential improvement strategies."
  • Developing a plan for the "Do" stage: Deciding who will do what, when, and how you will measure the results.

• Do: This is the implementation phase. It's where you carry out the plan, but in a small, controlled way. The text refers to this as "small 'tests of change'." The key here is to avoid making a large-scale change immediately. Instead, you test the strategy on a limited basis to see how it works and to minimize potential disruption or negative consequences if it fails.

• Check: This is the evaluation phase. After the small-scale test is complete, you "check" the results to see if the changes had the desired effect. This involves:

  • Measuring the outcomes: Using the metrics you established in the "Plan" stage to gather data.
  • Comparing the results to your goals: Did the strategy "make a difference"? Did it solve the problem or move you closer to your goal?
  • Analyzing the data: What did you learn? What worked well, and what didn't?

• Act: This is the final phase, where you decide what to do next based on the results from the "Check" phase. There are three main possibilities:

  • If the change was successful: You "act on the results" by standardizing the change and implementing it on a wider scale. This becomes the new, improved process.
  • If the change was not successful: You "act on the results" by going back to the "Plan" stage. You use the knowledge you gained from the test to revise your strategy and start the cycle over again.
  • If the results are promising but need more refinement: You can "act" by making adjustments and running another small test, effectively restarting the cycle.

In summary, the PDCA cycle is a systematic, iterative process for continuous improvement. It promotes a culture of learning and experimentation, allowing organizations to make changes incrementally, learn from their experiences, and refine their processes over time without taking large, risky leaps.

"Swiss cheese" model, a framework developed by James Reason to understand how accidents happen. The core idea is that in any complex system (like a hospital, an airline, or a factory), there are multiple layers of defenses, safeguards, and barriers designed to prevent accidents.

Here's a breakdown of the key concepts:

• Layers of Defense: Imagine these defenses as slices of Swiss cheese stacked on top of each other. Each slice represents a different safeguard. In a healthcare setting, these could be things like:

  • Procedures and policies: Rules for how tasks should be performed.
  • Training: Ensuring staff know how to do their jobs correctly.
  • Equipment: Using safety-tested and well-maintained tools.
  • Supervision: Having experienced managers overseeing operations.

• Latent Failures: The "holes" in each slice of Swiss cheese represent weaknesses or "latent failures" within that layer of defense. These are not active mistakes made by a person at the moment of the accident, but rather underlying systemic problems that have been present for some time. They are "dormant" and may not cause harm on their own.

  • The example given in the text is a great illustration: a wet floor is a latent failure in the physical environment. It's a potential hazard. Being unusually busy is another latent failure, this time in the system's operational capacity, which might lead to staff being distracted or rushed.

• The Accident: An accident occurs when, by chance, all the holes in the different slices of Swiss cheese line up. This creates a clear path for a hazard to pass through all the defenses and lead to a negative outcome.

  • In the example of a fall:
    1. The first slice (e.g., policy) might have a "hole" because there's no clear rule about immediate spill cleanup in a high-traffic area.
    2. The second slice (e.g., staff attention) might have a "hole" because a nurse is unusually busy (a latent failure) and doesn't notice the spill.
    3. The third slice (e.g., equipment) might have a "hole" because the "wet floor" sign is in a hard-to-see location.
    4. The fourth slice (e.g., patient awareness) might have a "hole" because the patient is distracted.

  When all these holes align, the patient falls.

In essence, the Swiss cheese model shifts the focus of accident investigation from blaming the individual who made the final error (the "active failure") to understanding the systemic weaknesses (the "latent failures") that allowed the error to occur in the first place. It shows that accidents are rarely the result of a single mistake, but rather the culmination of a series of pre-existing vulnerabilities in the system.

The leading causes of age-specific mortality:

• For individuals aged 15–24, the leading causes of mortality are:

  • Accident
  • Homicide
  • Suicide
  • Malignancy
  • Heart disease

• For individuals aged 25–44, the leading causes of mortality include:

  • Accident
  • Malignancy
  • Heart disease
  • Suicide
  • Homicide
  • HIV

• For individuals aged 45–64, the leading causes of mortality are:

  • Malignancy
  • Heart disease
  • Accident
  • Diabetes mellitus
  • Cerebrovascular disease
  • Chronic lower respiratory disease
  • Chronic liver disease and cirrhosis
  • Suicide

• For individuals aged ≥65, the leading causes of mortality are:

  • Heart disease
  • Malignancy
  • Cerebrovascular disease
  • Chronic lower respiratory disease
  • Alzheimer’s disease
  • Influenza and pneumonia
  • Diabetes mellitus
  • Kidney disease
  • Accidents
  • Septicemia

U.S. Preventive Services Task Force (USPSTF) recommends preventive counseling for the following conditions and topics:

• Alcohol and drug use
• Genetic counseling for BRCA1/2 testing among women at increased risk for deleterious mutations
• Nutrition and diet
• Sexually transmitted infections
• Sun exposure
• Tobacco use

• Up to age 27:
  • Human papillomavirus (HPV) immunization: Recommended if not done prior.
• Women planning or capable of pregnancy:
  • Folic acid chemoprevention: For the prevention of neural tube defects in the baby.
• Aged >18 years:
  • COVID-19 immunization.
  • Influenza immunization: Recommended yearly.
  • Tetanus-diphtheria immunization: Recommended every 10 years.
  • Varicella immunization: Two doses for susceptibles only.
  • Measles-mumps-rubella (MMR) immunization: One dose for women of childbearing age.
• Aged 40–59 years:
  • Aspirin chemoprevention: For cardiovascular disease, specifically for those with a ≥10% 10-year cardiovascular disease risk (note: bleeding risk may equal benefit for some groups).
• Aged >60 years:
  • Zoster immunization: Recommended once.
• Aged >64 years:
  • Pneumococcal immunization: 20 valent option or 15/23.
  • Vitamin D chemoprevention: For fracture/falls, specifically for those at increased risk for falls.
• Women at high risk for breast cancer:
  • Tamoxifen/raloxifene chemoprevention: For breast cancer.

U.S. Preventive Services Task Force: Screening Tests by Age Group

I. Young Adults / Specific Risk Groups (Starting Ages up to 20s)

• Sexually active women <25

  • Condition: Chlamydia/Gonorrhea
  • Test: Nucleic acid amplification test on urine or cervical swab
  • Frequency: Unknown

• Adults 15–65

  • Condition: HIV
  • Test: Reactive immunoassay or rapid HIV followed by confirmatory test
  • Frequency: At least once

• Adults 18–79

  • Condition: Hepatitis C
  • Test: Anti-HCV antibody followed by confirmatory PCR
  • Frequency: Once

• Women 21–65

  • Condition: Cervical cancer
  • Test: Pap smear
  • Frequency: Every 3 years

• Women of childbearing age

  • Condition: Intimate partner violence
  • Test: Screening questions
  • Frequency: Unknown

II. Middle-Aged Adults (Starting Ages 30s to 50s)

• Women 30–65

  • Condition: Cervical cancer
  • Test: Pap smear and/or HPV testing
  • Frequency: Every 5 years if HPV negative

• Adults 40–75

  • Condition: Hyperlipidemia
  • Test: Cholesterol
  • Frequency: Unknown

• Adults 45–75

  • Condition: Colorectal cancer
  • Tests & Frequencies:
    • Fecal occult blood testing: Every year
    • Fecal immunochemical-DNA: Every 1–3 years
    • Sigmoidoscopy: Every 5 years
    • Colonoscopy (or occult blood testing combined with sigmoidoscopy): Every 10 years

• Women (40?) 50–75

  • Condition: Breast cancer
  • Test: Mammography with or without clinical breast examination
  • Frequency: Every 2 years (Note: While 50-75 is the primary range listed, 40 is also mentioned parenthetically.)

• Adults 50–80 years who have a 20-pack-year smoking history and currently smoke or have quit within the past 15 years

  • Condition: Lung cancer
  • Test: Low-dose computed tomography
  • Frequency: Yearly

III. Older Adults (Starting Ages 60s and Above)

• Men 65–75 who have ever smoked

  • Condition: Abdominal aortic aneurysm
  • Test: Ultrasound
  • Frequency: Once

• Women >65 or >60 with risk factors

  • Condition: Osteoporosis
  • Test: DEXA
  • Frequency: Unknown

IV. General Adult Population (Applicable Across Broad Age Ranges)

• All adults

  • Conditions & Tests:
    • Alcohol misuse: Alcohol Use Disorders Identification Test
    • Depression + Anxiety: Screening questions
    • Hypertension: Blood pressure
    • Obesity: Body mass index
  • Frequency: Unknown for Alcohol Misuse and Obesity; Periodically for Depression + Anxiety and Hypertension.

• Adults overweight, obese, or with hypertension

  • Condition: Diabetes
  • Test: Fasting blood glucose or HgbA1c
  • Frequency: Every 3 years

Principles of Screening for Disease

• The condition being screened for should be an important health problem.
• There should be an available treatment for the condition.
• Facilities for diagnosis and treatment must be accessible.
• The disease should have a latent stage.
• A test or examination for the condition needs to exist.
• The screening test should be acceptable to the population.
• The natural history of the disease should be sufficiently understood.
• There must be an agreed policy on whom to treat.
• The cost of finding a case should be balanced against the overall medical expenditure.

Categorizing test results based on a patient's actual disease status.

The foundation of these measures is a table that cross-references the TEST RESULT (Positive or Negative) with the DISEASE STATUS (PRESENT or ABSENT). This cross-tabulation yields four possible outcomes:

• True positives (TP): When the test result is positive, and the disease is actually present.
• False positives (FP): When the test result is positive, but the disease is actually absent.
• False negatives (FN): When the test result is negative, but the disease is actually present.
• True negatives (TN): When the test result is negative, and the disease is actually absent.

Based on these outcomes, the sources define the following test characteristics:

Test Characteristics in Patients with Disease

These measures describe how well the test identifies individuals who have the disease.

• True-positive rate (sensitivity):

  • This measures the proportion of people with the disease who test positive.
  • The formula is TP / (TP + FN).
  • In simpler terms, it's the ability of the test to correctly identify those with the condition.

  • False-negative rate:

  • This measures the proportion of people with the disease who test negative.

  • The formula is FN / (TP + FN).
  • It is also equal to 1 – true-positive rate.
  • This represents the likelihood of missing a true case of the disease.

Test Characteristics in Patients without Disease

These measures describe how well the test identifies individuals who do not have the disease.

• True-negative rate (specificity):

  • This measures the proportion of people without the disease who test negative.
  • The formula is TN / (TN + FP).
  • It indicates the ability of the test to correctly identify those without the condition.

  • False-positive rate:

  • This measures the proportion of people without the disease who test positive.

  • The formula is FP / (TN + FP).
  • It is also equal to 1 – true-negative rate.
  • This represents the likelihood of incorrectly identifying someone as having the disease when they do not.

This tool is designed to simplify the process of calculating the posttest probability of a disease.

Here's a breakdown of the key concepts and how to use the nomogram based on the description:

• Bayes' Theorem: This is a fundamental principle in probability that allows you to update the probability of a hypothesis (in this case, the presence of a disease) after new evidence (a test result) is taken into account. The nomogram is a visual shortcut for this calculation.

• Nomogram Components: The nomogram consists of three parallel scales:

  1. Pretest Probability of Disease (Left-hand scale): This is the probability that a patient has the disease before the diagnostic test is performed. This is often estimated based on factors like the patient's symptoms, age, sex, and medical history.

  2. Likelihood Ratio (Middle scale): This is a key measure that quantifies how much a test result changes the probability of a disease.

     • Likelihood Ratio for a Positive Test (LR+): Indicates how much more likely a positive test result is in a patient with the disease compared to a patient without the disease. A higher LR+ means a positive result is more informative and strongly suggests the presence of the disease.

     • Likelihood Ratio for a Negative Test (LR-): Indicates how much less likely a negative test result is in a patient with the disease compared to a patient without the disease. A lower LR- means a negative result is more informative and strongly suggests the absence of the disease.

  3. Posttest Probability of Disease (Right-hand scale): This is the updated probability that the patient has the disease after the test result is known.

• How to Use the Nomogram: The text provides a simple, three-step process:

  1. Identify the Pretest Probability: Locate the patient's pretest probability on the left-hand scale.

  2. Identify the Likelihood Ratio: Find the likelihood ratio corresponding to the test result (e.g., LR+ for a positive test) on the middle scale.

  3. Connect and Read: Place a straightedge (like a ruler) to connect the pretest probability point and the likelihood ratio point. The point where the straightedge intersects the right-hand scale is the posttest probability.

• Example from the Text: The text provides a specific example to illustrate the nomogram's use:

  • Scenario: A patient has a pretest probability of coronary artery disease of 50%.

  • Test 1: Positive Exercise Treadmill Test:

    • Likelihood Ratio (LR+) = 4.

    • The green line on the nomogram connects the 50% pretest probability to the LR+ of 4.

    • The intersection point on the right-hand scale gives the new, higher posttest probability.

  • Test 2: Positive Exercise Thallium Single-Photon Emission CT Perfusion Study:

    • Likelihood Ratio (LR+) = 9.

    • The broken brown line connects the same 50% pretest probability to the higher LR+ of 9.

    • Because the likelihood ratio is higher (9 vs. 4), the straightedge will point to a significantly higher posttest probability on the right-hand scale. This demonstrates that the thallium study is more diagnostically valuable than the exercise treadmill test in this scenario.

In summary, the nomogram is a practical, visual tool that simplifies a complex calculation (Bayes' theorem) to help clinicians quickly and easily estimate the probability of a disease after a diagnostic test is performed, using the pre-test probability and the test's likelihood ratio.

A graphical plot used to assess the diagnostic ability of a binary classifier system as its discrimination threshold is varied.

Here's a breakdown of the key concepts from the text:

• ROC Curve: It's a graph that visualizes the trade-off between a test's sensitivity and specificity.

  • Sensitivity: Also known as the true positive rate, it measures the proportion of actual positive cases (patients with the disease) that are correctly identified as such.

  • Specificity: Also known as the true negative rate, it measures the proportion of actual negative cases (patients without the disease) that are correctly identified as such.

  • The Trade-off: The curve is generated by changing the "test value" or threshold that determines whether a result is considered "positive" or "negative." As you adjust this threshold, you will see that improving sensitivity often comes at the cost of decreasing specificity, and vice versa. The ROC curve captures this relationship across all possible thresholds.

• The 45° Line: This diagonal line, running from the bottom-left corner to the top-right corner, represents a test with no predictive power. A test that falls on this line has a sensitivity equal to its specificity at every threshold. This is essentially a random guess, as the test's ability to correctly identify a patient with the disease is no better than its ability to correctly identify a patient without the disease.

• Area Under the Curve (AUC): The area under the ROC curve is a single numerical value that summarizes the overall diagnostic accuracy of the test.

  • Interpretation: The AUC value ranges from 0 to 1.

    • An AUC of 1.0 indicates a perfect test that can distinguish between positive and negative cases with 100% accuracy.

    • An AUC of 0.5 corresponds to the 45° line, indicating a test with no diagnostic value.

    • An AUC between 0.5 and 1 indicates that the test has some predictive value, and a larger AUC signifies a more accurate test.

In essence, the ROC curve and its AUC provide a comprehensive way to evaluate and compare the performance of different diagnostic tests, helping clinicians and researchers determine which test is most effective for a given purpose.

• STRONG VACCINE RECOMMENDATION
• TAILORED COMMUNICATION
• TRANSPARENCY AND ACCURACY
• SUPPORT FROM ACCESSIBLE INFORMATION SOURCES

• REVISITING AND REINFORCEMENT OF THE RECOMMENDATION

• STRONG VACCINE RECOMMENDATION: Clearly and unequivocally recommend vaccines as the best protection against serious diseases, even if a patient is initially uncomfortable.

• TAILORED COMMUNICATION: Customize the conversation by addressing individual patient histories, specific concerns, and fears, such as vaccine effectiveness across different backgrounds or needle phobia.

• TRANSPARENCY AND ACCURACY: Be transparent about potential side effects while accurately contextualizing their rarity and comparing them to disease risks, and provide factual information on vaccine components and efficacy.

• SUPPORT FROM ACCESSIBLE INFORMATION SOURCES: Provide patients with reliable, accessible information from vetted sources, guiding them away from inaccurate online content and offering resources tailored to specific communities.

• REVISITING AND REINFORCEMENT OF THE RECOMMENDATION: Conduct ongoing discussions by following up on previous recommendations, checking on vaccination experiences, and addressing any reported adverse reactions.

patients who reject the vaccine:

• refusers

• late and selective

patients who accepts the vaccines:

• hesitant with many doubts and concerns

• hesitant with minor doubts and concerns

• active demand with no doubts and concern

Participatory communication approach is for the ones who reject.

Presumptive communication approach is for the ones who accept.

Key Definitions of Physical Activity Types:

• Moderate-intensity physical activity:
  • Aerobic activity that increases heart rate and breathing to some extent.
  • On a 0-10 scale, it's typically a 5 or 6.
  • Examples: Brisk walking, dancing, swimming, or bicycling on a level terrain.
• Vigorous-intensity physical activity:
  • Aerobic activity that greatly increases heart rate and breathing.
  • On a 0-10 scale, it's typically a 7 or 8.
  • Examples: Jogging, singles tennis, swimming continuous laps, or bicycling uphill.
• Muscle-strengthening activity:
  • Physical activity, including exercise, that increases skeletal muscle strength, power, endurance, and mass.
  • Includes strength training, resistance training, and muscular strength and endurance exercises.
• Bone-strengthening activity:
  • Physical activity that creates an impact or tension force on bones, which promotes bone growth and strength.
  • Examples: Running, jumping rope, and lifting weights.

Physical Activity Recommendations by Age Group:

1. Preschool-aged Children (Ages 3–5 years)

• Recommendation: Should be physically active throughout the day to enhance growth and development.
• Caregiver Role: Adult caregivers should encourage active play that includes a variety of activity types.

2. Children and Adolescents (Ages 6–17 years)

• General: Provide opportunities and encouragement for activities that are age-appropriate, enjoyable, and varied.
• Daily Goal: Should do 60 minutes (1 hour) or more of moderate-to-vigorous physical activity daily.
• Specific Activity Types (as part of the 60+ minutes daily):
  • Aerobic:
    • Most of the 60+ minutes should be moderate- or vigorous-intensity aerobic physical activity.
    • Include vigorous-intensity physical activity on at least 3 days a week.
  • Muscle-strengthening:
    • Include on at least 3 days a week.
  • Bone-strengthening:
    • Include on at least 3 days a week.

3. Adults (Ages 18–64 years)

• General: Move more and sit less throughout the day; any amount of physical activity offers health benefits.
• Aerobic Activity for Substantial Health Benefits:
  • At least 150 minutes (2 hours and 30 minutes) to 300 minutes (5 hours) a week of moderate-intensityaerobic physical activity.
  • OR at least 75 minutes (1 hour and 15 minutes) to 150 minutes (2 hours and 30 minutes) a week of vigorous-intensity aerobic physical activity.
  • OR an equivalent combination of both.
  • Preferably, aerobic activity should be spread throughout the week.
• Additional Health Benefits: Gained by engaging in physical activity beyond the equivalent of 300 minutes (5 hours) of moderate-intensity activity a week.
• Muscle-strengthening Activities:
  • Do activities of moderate or greater intensity that involve all major muscle groups.
  • Perform on 2 or more days a week for additional health benefits.

4. Older Adults (Ages ≥65 years)

• General: The key guidelines for adults (18-64 years) also apply to older adults.
• Additional Key Guidelines for Older Adults:
  • Multicomponent Physical Activity: As part of weekly physical activity, older adults should do multicomponent physical activity that includes balance training, as well as aerobic and muscle-strengthening activities.
  • Effort Level: Should determine their level of effort relative to their level of fitness.
  • Chronic Conditions: Older adults with chronic conditions should understand how their conditions affect their ability to safely do regular physical activity.
  • If unable to meet 150 minutes of moderate-intensity aerobic activity: They should be as physically active as their abilities and conditions allow.

Overall Guideline:

• Follow a healthy dietary pattern at every life stage.

Dietary Patterns by Life Stage:

• First 6 months of life: Infants should exclusively be fed human milk.
  • If human milk is unavailable, use iron-fortified formula.
• From 6 to 12 months: Infants should be introduced to a variety of complementary nutrient-dense foods.
• From 12 months to older adulthood: The dietary pattern should meet nutrient needs, help achieve a healthy body weight, and reduce the risk of chronic disease.

Key Recommendations for Healthy Eating Patterns:

1. Customize and enjoy nutrient-dense food and beverage choices.

   • Choices should reflect personal preferences, cultural traditions, and budgetary considerations.
   • The Dietary Guidelines offer a framework that can be customized to individual needs and diverse cultures.

   • Focus on meeting food group needs with nutrient-dense foods and beverages, and stay within calorie limits.

   • Nutrient-dense foods provide vitamins, minerals, and other health-promoting components.

   • They have no or little added sugars, saturated fat, and sodium.
   • A healthy dietary pattern includes nutrient-dense forms of foods and beverages across all food groups, in recommended amounts, and within calorie limits.

   • Limit specific components in foods and beverages:

   • Limit foods and beverages higher in added sugars, saturated fat, and sodium.

   • Limit alcoholic beverages.
   • Meeting food group recommendations with nutrient-dense choices typically fulfills most daily calorie and sodium needs, leaving little room for excess added sugars, saturated fat, sodium, or alcohol.

   • Apply the Key Recommendations in their entirety.

   • Each dietary component is interconnected with others.

   • These guidelines provide a framework to accommodate personal preferences, cultural traditions, and budgetary considerations.
   • The focus is on meeting food group needs with nutrient-dense options, within calorie limits, to achieve a healthy weight and reduce the risk of chronic disease.

Core Elements of a Healthy Dietary Pattern (What to Include):

• Vegetables: All types, including dark green; red and orange; beans, peas, and lentils; starchy; and other vegetables.
• Fruits: Especially whole fruit.
• Grains: At least half of which are whole grain.
• Dairy: Includes fat-free or low-fat milk, yogurt, and cheese.
  • Lactose-free versions and fortified soy beverages and yogurt are acceptable alternatives.
• Protein foods: Includes lean meats, poultry, and eggs; seafood; beans, peas, and lentils; and nuts, seeds, and soy products.
• Oils: Includes vegetable oils and oils found naturally in food, such as seafood and nuts.

Limits for a Healthy Eating Pattern:

• Added sugars:
  • Less than 10% of calories per day starting at age 2.
  • Avoid foods and beverages with added sugars for those younger than age 2.
• Saturated fat:
  • Less than 10% of calories per day starting at age 2.
• Sodium:
  • Less than 2300 mg/day.
  • Even less for children younger than age 14.
• Alcoholic beverages:
  • Adults of legal drinking age can choose not to drink, or to drink in moderation.
  • Limit intake to 2 drinks or less in a day for men.
  • Limit intake to 1 drink or less in a day for women, when alcohol is consumed.
  • Drinking less is better for health than drinking more.
  • Some adults, such as women who are pregnant, should not drink alcohol.

Physical Activity Recommendation:

• Meet the U.S. Department of Health and Human Services’ Physical Activity Guidelines for Americans.
  • Applies to Americans of all ages (children, adolescents, adults, and older adults).
  • Helps promote health and reduce the risk of chronic disease.
  • Aim to achieve and maintain a healthy body weight.
  • The relationship between diet and physical activity contributes to calorie balance and managing body weight.

• extra cytoplasmic outer membrane - has lipid bilayer with associated proteins, lipoproteins and polysaccharides.
• polysaccharides include capsule and LPS.
• outer membrane components are the usual determinants of virulence and antimicrobial resistance.
• secreted products are important for host infection, environmental niche survival and colonisation.

• in the long term are facilities and hospitals, with the excessive use of antibiotics, GNBs are emerging as major colonisers.
• this colonisation will lead to subsequent extra intestinal infection.

bacteria that can be acquired through contaminated infusates: - serratia. - enterobacter. - citrobacter.

fresh water and marine environment: edwardseilla.

• carbapenem resistant Enterobacterales - urgent - priority one - critical threat.

list the gram negative Enterobacterales causing extra intestinal infections

• Escherichia coli.
• Klebisella
• Proteus
• Enterobacter
• Serratia
• Citrobacter
• Morganella
• Providentia.
• Cronobacter
• Edwardsiella.

list the gram negative Enterobacterales causing intestinal infections

• Shigella
• Salmonella
• Yesenia.

in a healthy human E. coli is the predominant species of GNB in the colonic microbiota f/b klebsiella and enterobacter.

chemoprophylaxis

• risk of transmission to house hold contacts is extremely high.
• all the household contacts should be immunised irrespective of the immunization status.
• erythromycin estolate 50mg/kg/day upto a maximum dose of 1gm/day was effective in reducing the incidence of bacteriologically confirmed pertussis by 67% but there was no decrease in the incidence of the clinical disease.
• newer macrolides for prophylaxis Data is lacking - may be used.

immunization

• mainstay of prevention is pertussis vaccine.

whole cell pertussis vaccine:

• it is prepared through heating, chemical inactivation and purification of the B. pertussis.

uncommon side effects: - febrile seizures - hypotonic hyporesponsive syndrome.

acellular pertussis vaccine.

• all contain pertussis toxoid and filamentous heamagglutinin.
• is used exclusively for childhood immunization in much of the developed world.
• the problem is early weaning of the acquired immunity.
• so if children are given acellular vaccine - additional boosters are required for: older children, adult, adolescent.

why in pregnancy?

• to increase passive transfer to fetus.
• it is 90-93% effective in preventing pertussis in infants <2mo old.

what are the recommended regimens?

• three dose primary series: 2, 4, 6 mo.
• reinforcing dose: 15-18 mo.
• booster dose: 4-6 years.
• 11-18yr adolescents and all unvaccinated adults: one dose of Tdap.
• healthcare workers, paediatricians, people working in paediatric facilities are more indicated.
• in pregnancy 27-36 weeks - the earlier in the range, the better.

antibiotics: therapy is to eradicate the organism. unless given in early course of catarrhal phase, therapy has no effect on clinical course of the disease. - DOC: macrolides. - if allergic: TMP-SMX. - macrolide resistance - rare.

age <1month:

azithromycin: - recommended agent. - 10mg/kg/day OD X 5 days.

erythromycin : - not preferred. - use only if azee is not available.

clarithromycin: - not recommended.

TMP-SMX: - C/I <2mo age.

1-5 months age:

• azithromycin.
• erythromycin.

clarithromycin - 15mg/kg/day in 2 divided doses. X 7 days.

TMP-SMX: - only if ≥2months. - TMP 8mg/kg/day - SMZ 40 mg/kg/day. - in 2 divided doses X 14 days.

infants ≥6months and children:

azithromycin: - 10mg/kg/day on day 1 STAT. - f/b 5mg/kg/day OD max 500mg on days 2-5.

erythromycin: - 40-50 mg/kg/day. - max 2g/day. - in 4 divided doses X 14 days.

clarithromycin. - 15mg/kg/day - max: 1gm/day. - in 2 divided doses X 7 days.

TMP-SMX: - 8mg/kg/day TMPin 2 divided doses X14 days.

adults:

azithromycin. - 500mg day 1 f/b 250mg day 2-5.

erythromycin: - 2gm/day in 4 divided doses X14 days.

clarithromycin: - 500mg BD X7 days.

TMP-SMX: - TMP 320mg/SMX 1600mg / day in 2 divided doses X 14 days.

adverse effects:

azithromycin: - abdominal discomfort. - caution in cardiac cases.

erythromycin: - increased gastric motility. - hypersensitivity.

clarithromycin: - epigastric distress and cramps.

TMP-SMX: - effectiveness data limited. - use in pts allergic to macrolides.

supportive care - infants - high risk of death - hospitalise. - maintain quiet environments - decreases the paroxysmal stimulation. - beta blockers and steroids - advided by few authorities - but use case not clear. - cough suppressants - not effective.

infection control measures: - respiratory isolation. - continue for 5 days after initiation of the macrolide therapy. - in untreated patients - for 3 weeks - i.e. nasopharyngeal cultures are persistently negative.

particularly in age <1year, if isolated in patients of clinical infection of pertussis, represent co infection: - RSV - rhinovirus. - adenovirus

in adults and adolescents, suspect pertussis when: - cough not improving with in 14 days. - paroxysmal cough of any duration. - cough f/b vomiting. - any respiratory symptoms after contact with lab confirmed pertussis.

non infective causes of prolonged cough: - ACEi - reactive airway disease - GERD

• lymphocytosis >10^8 to 10^9/L is suggestive in young children.
• gold standard: culture of nasopharyngeal secretions. TAT ~5days
• multi target DNA PCR has primers for Bordetella pertussis, Bordetella parapertussis, Bordetella holmesii.
• best specimen: nasopharyngeal aspirate.

procedure: - fine flexible plastic catheter is used. - it is attached to a 10mL syringe. - passed into the nasopharynx. - withdrawn with gentle suction.

appropriate medium: - bordet-gengou - regan Lowe.

precautions while collection: - B. pertussis is susceptible to drying. - inoculate the sample onto the media immediately or. - flush the catheter with phosphate buffered saline solution. - if rayon or Dacron swabs are used - utilise transport medium - Regan-Lowe charcoal medium.

if untreated nasopharyngeal cultures are positive for ~3 weeks.

if treated - the become negative by day 5

much of the period of organism detection falls into the catarrhal phase.

in patients symptomatic for >4 weeks: - serologic diagnosis is preferred. - EIA detecting IgA IgG to: - pertussis toxin - filamentous haemagglutinin - pertactin - fimbriae.

two or four fold raise in the titres are suggestive of pertussis

cross reactivity can occur between few antigens such as filamentous heamagglutinin an pertectin

particularly in the outbreak setting antibodies to pertussis toxin are being standardised

• more common among infants.
• sub conjunctival haemorrhage.
• hernias
• pneumothoraces.
• facial and truncal petechiae.
• weight loss secondary to severe caloric deficit.
• urinary incontinance.
• rib fracture.
• carotid artery aneurysm.
• cough syncope.

most common complication in children <2years of age is - apnea.

except for infants, in all other age groups pneumonia is secondary to superimposed bacterial infections. and the most common causes are: encapsulated organisms streptococcus pneumoniae and haemophillus influenzae

• classic pertussis is seen usually among pre school and school age children.
• incubation period 7-10 days.

phase 1: catarrhal phase: - indistinguishable from common cold. - coryza. - lacrimation. - mild cough. - low grade fever. - malaise.

phase 2: paroxysmal phase: - cough becomes frequent, spamodic. - repetitive bursts of 5-10 coughs, usually with a single expiration. - post tussle vomiting is frequent with mucus plug. - episode terminates with a audible whoop. - the whoop is because of forceful inspiration against a closed glottis.

associated features with spasm: - neck vein dilations. - bulging eyes. - tongue protrusion. - cyanosis.

so what can precipitate a paroxysm? - touching - noise - eating.

how is the variation through the day? - frequency is widely variable. - worse at night. - interfere with sleep.

most complications occur during the paroxysm stage.

fever is uncommon and suggests bacterial super infection.

phase 3: convalescent phase - after 2-4 weeks. - last 1-3 months. - gradual resolution of the symptoms. - f/b 6-12 mo of intercurrent viral illnesses with recrudescence of paroxysmal cough. - in adults and adults paroxysmal cough is usually present. but the whoop is the least expected symptom.

• both humoral and adaptive play role.
• immunity is not life long. subsequent episodes are prevented due to subsequent subclinical infections.
• serologic correlates of pertusis vaccine are not clear.
• antibodies to pertactin, fimbriae, and to a lesser degree pertussis toxin correlates close.

duration of immunity: - after whole cell vaccine: 10-12 years. - after a complete course of acellular vaccines - in adolescents and adults - 2-4 years after the 5th or 6th dose.

type of response ellicited: - natural infection and whole cell vaccine: TH1/TH17 predominant response. - acellular vaccine: TH2 biased response.

how does the infection begin? - with the attachment of the organism to the ciliated epithelial cells.

how does the organism attach? - by the help of adhesins.

where do the adhesins bind to? - they bind to the integral family of the cell surface proteins, probably in conjunction with the pertussis toxin. - the role of fimbriae in attachment and maintenance is still not delineated.

what happens after the attachment? - the organism multiply. - produces toxins like tracheal cytotoxin and dermonecrotic toxin which damage the local mucosa. - pertussis toxin and adenylate cyclase haemolytic toxins impair the host defences. - organism invades the local cells and become intracellular.

it is of importance that the bacteria does not invade systemically. the systemic symptoms are secondary to toxins.

• it is not known what causes the hallmark paroxysmal cough.
• it is thought that the neurologic manifestations of seizures and encephalopathy is possibly due to hypoxia from the coughing paroxysms or apnea.
• pneumonia seen in about 22% of the infants is a diffuse bilateral disease.
• in old children and adults - pneumonia is usually due to secondary bacterial infections with streptococci or staphylococci.

deaths in young infants is usually associated with very high leukocytosis and pulmonary hypertension.

• it is a highly communicable disease.
• attack rates 80-100% in the unimmunized household contacts. 20% within household well immunised contacts.
• shows cyclical outbreaks every 3-5 years.
• 90% of the disease burden is in the developing nations.
• it can affect individuals of all age groups.
• in a highly immunised population - the peak incidence is among the infants who have not yet completed the 3 dose primary schedule.
• asymptomatic pertussis infection is ~56%, appears to contribute to the disease transmission.
• school age children are the source of infection in most house holds.
• adults are the source of infection for high risk infants and are the reservoirs of infection between epidemic years.

• 10 species area identified.

clinically important species: - Bordetella pertussis. - Bordetella parapertussis. - Bordetella holmesii. - Bordetella bronchiseptica. - mainly a zoonotic organism.

in immunocompromised - occasionale pathogens: - B. petrii. - B. hinzii. - B. ansorpii.

Bordetlla pertussis: - gram negative. - pleomorphic. - aerobic. - bacilli. - slow growing. - fastidious. - forms glistening bifurcated colonies. - can be identified by fluorescent antibody testing or agglutination with specific antiserum.

toxins and biologically active products: - most of the virulence factors are under the control of a single gene locus which regulates their production. - the most important virulence factor is the pertussis toxin. - B. parapertusis do not encode the gene for pertussis toxin.

other virulence factors and adhesins are: - filamentous heamagglutinin - component of the cell wall. - pertactin - outer membrane protein. - fimbriae - bacterial appendages. play a role in the attachment. the major antigens against which the agglutination antibodies are detected. these agglutination antibodies are primary means for the serotyping. - tracheal cytotoxin - peptidoglycan fragment - it is responsible for the respiratory epithelial damage. - adenylate cyclase haemolytic toxin - it impairs the host phagocytic cell function contributing to the respiratory mucosal damage. - lipooligosacharide - acts as an enotoxin.

pertussis toxin: - it has a B oligomer binding subunit. - it also has a enzymatically active A promotor. - the promotor ADP ribosylate guanine nucleotide binding regulatory protein G protein in the target cells. - it has mitogenic activity. - affects the circulating lymphocytes. - serves as adhesin for bacterial binding to the respiratory ciliated cells.

pertactin containing acellular pertussis vaccines have caused selective pressure leading to the development of pert actin negative strains.

• acute infection of the respiratory tract.
• caused by Bordetella pertussis.
• whooping cough is uncommon ≤ 6months of age, older children and in adults.
• also called the 100 day cough.

prevention plans require: - identification of the high risk areas. - identification of at risk structures. - implementation and monitoring of control methods. - methods for intervention if control systems fail. - procedures to assure documentation that policies are followed.

even if detected, legionella becomes a pathogen only after replication in the premise plumbing system.

• for cooling towers: high efficiency drift eliminators and routine maintenance is mandate.

can construction work increase the risk? - yes. - it increases the water stagnation. - modification of the existing plumbing work can disrupt the existing biofilms. - new facilities can become colonised and later lead to a out break.

what to do if a presumptive or possible healthcare associated pneumonia is detected? - first thing to do is testing for legionella. - environmental cultures are gold standard because they help quantify the levels, allow species identification / serotyping and can link environmental sources with the outbreak. - first test the possible sources of exposure - if positive - extend the testing area. - also frame the management plan to address the outbreak. - select high risk sites should. b e tested biannually or quarterly.

what to do after identification of the common source? - immediate limitation of the ongoing water exposure. - removing or replacing the water features associated. - interventions include: heatshock - increasing the water temperature for a certain period, and hyperchlorination. these are short term steps.

chemical disinfection agents: secondary methods. - chlorine. - monochloramine. - copper and silver ionisation.

monitor chemical or ion levels to make sure they are sufficient

third option: - water filtration. - it can be used as a primary method or as a combination for the secondary methods. - filters can be placed in the line of plumbing or at the points of use. - the problems with these systems is, the filters are expensive, require regular maintain ace and can reduce at the water pressure.

• case fatality rates are ~10%.
• if antibiotics are delayed - mortality rates are 3X higher.
• in cases of nosocomial pneumonia esp secondary to Legionella pneumophilia are ~25%.
• in immunocompromised cases mortality rates are ~30-50%

~25% have long term complications:

• recurrent hospitalisations.
• acute renal failures.
• respiratory complications.
• recurrent pneumonias.

recovery from Pontiac fever is with in 3-5 days.

• use antibiotics which target the intracellular pathogens.
• patients with pontiac fever do not require antibiotic therapy.
• first line agents: macrolides and fluroquinolones.
• azithromycin is the preferred agent.
• azithro and clarithro reach higher intracellular conc compared to erythromycin.

treatment options

• fluroquinolones: levofloxacin/ ciprofloxacin/ moxifloxacin

• macrolide: azithromycin/ clarithromycin

• levofloxacin 750mg OD. PO in mild and IV in moderate/severe disease.

• ciprofloxacin 500mg BD. PO in mild and IV in moderate/severe disease.
• moxifloxacin 400mg OD-PO in mild and BD in moderate/severe disease.
• azithromycin 500mg OD day 1 f/b 250mg OD for a minimum of 4 days in mild disease and 500mg IV OD in moderate/severe disease.

• clarithromycin 400mg OD-PO in mild and BD-IV in moderate/severe disease.

• irrespective of the severity of the disease - all immunosupressed should receive the IV therapy.

• switch to oral regimen if the condition improves.
• also in severe disease consider dual therapy: either dual fluroquinolones, dual macrolides or either agent with another secondary agents.

secondary agents - doxycycline. - minocycline. - rifampin. - TMP-SMX. (less frequent)

note

• in non randomized trials: fluroquinolones are shown to be more effective in terms of fever resolution and decreased duration of hospitalization.

• tigecycline can be used in patients with significant allergies.

• novel aminomethylcycline omadacycline - efficacious in vitro - not studied yet.

• optimal duration of treatment is not known.

• advised until clinical stability is achieved.
• minimum 5 days.
• in non pulmonary cases - duration should be dependant on the clinical outcomes.
• resistance to macrolides and fluroquinolones is rare.

radiographic findings:

CXR - focal infiltrates and consolidation. - mainly involves the lower lobes.

CT - ground glass opacities may be seen. in immunocompromised ± cavitations and pulmonary nodules

microbiology - Legionella micdadei can present with white colonies on buffered charcoal yeast. it is the only species which is modified acid fast. - the gold standard for diagnosis is culture. - Legionella requires special nutrients like cysteine for growth. - the specialized media for growth: buffered charcoal yeast extract BCYE agar. - growth 2-5 days. - colonies are fluoresence blue or white under UV light. - cultures are useful for serotyping.

urine antigen testing - urinary antigen is detected for serogroup 1. - sensitivity is only 70% so false positives are high.

where can we not use the test reliably: - early in the disease - will be negative. - in immunosuppressed - positive form months after infection. - in anuric cases.

not recommended for screening in asymptomatic cases during outbreak.

serology - useful during outbreak. - helps assess investigation of patients with non severe disease.

when is a case confirmed? - four fold or greater raise in serum specific antibody to Legionella pneumophilia serogroup 1.

when to suspect a case: 1. four fold or greater raise in the antibody titre to specific species or non serogroup 1 L. pneumohilia. 2. four fold or greater raise in the antibody titres to multiple species of Legionella.

a single antibody titres of ≥1:256 is also said to be sufficient by few authorities.

also the cavet is that around 20-30% of the infected patients fail to mount the antibody response.

direct fluroscent antibody testing - the sensitivity of DFA in sputum is the least compared to other modalities. - they target specifc species or serotypes. - has a high positive predictive value in patients with severe symptoms. so has no role inpatients with low risk cases.

molecular testing

modalities available: - PCR. - Loop mediated isothermal amplification. - nucleic acid amplification tests.

pcr methods cannot detect serotype.

• it is an influenza like illness.
• mild and self limiting.
• it is defined by absence of pneumonia.
• symptoms start after 24-48 hours and last for 2-5 days.
• mostly due to Legionella pneumophilia exposure.
• Legionella anisa is also associated.

extra pulmonary manifestations: - skin and soft tissue infections with tap water contamination of the surgical wounds. - culture. negative prosthetic valve endocarditis. - myocarditis. - pericarditis. - rarely: septic arthritis and sinusitis.

• pneumonia is the most common manifestation.
• it is an atypical pneumonia - lacks classic signs of broncho pneumonia.
• frequently associated with gastrointestinal and neurologic signs.

indications for legionella testing: - recent travel. - presentation during possible outbreak. - pneumonia when hospitalized. - presentation with severe manifestations like: sepsis, acute respiratory failure.

symptoms strongly associated with legionella pneumonia: - confusion - diarrohea - nausea / vomiting.

hospitalizatin rates: for pneumonia >90% and for pontiac fever <1%.

case fatality rates for pneumonia is ~10%. in immunosuppressed or with underlying lung infections: 30-50%

clinical findings are more apparent in immunosuppressed.

procalcitonin is not a useful marker for infection.

scoring systems: they are more useful for negative predictive value: - winthrop university hospital criteria. - legionella score.

definations: - presumptive healthcare associated: case of pneumonia where - with in the 14 days prior to the onset, the patient has a history of ≥10 days continuous stay in a hospital. - possible healthcare associated: patient with pneumonia, within the prior 14 days before onset, spent a considerable amount of time in one or more health care facilities, but the timeline does not meet he criteria of presumptive case.

CDC recomendations to evaluate healthcare setups for point of outbreak: - one or more presumptive healthcare associated legionnaires disease at any time. - two or more possible cases with in 12 months of one another.

in the recent days there is an increasing trend in the incidence of legionnaire's disease, this can be attributed to: - aging population. - improved diagnostics. - global temperature changes. - aging water infrastructure.

• 80% of the legionnaire's disease burden is attributed to the legionella pneumophilia serogroup 1.

• Legionella longbeachae is the emerging pathogen in australia and new zealand. its rates are on par or are exceeding L. pneumophilia.

other non pneumophilia organisms: - Legionella micdadei. - Legionella bozemanii. - Legionella longbeachae. - Legionella anisa.

risk factors for these non pneumophillia organisms are: - immunosupperssion - cancer. - transplant recepients.

when does it spread more? - in warm humid rainy climates. - in summer and fall. - seasonal stroms - disrupt the water pipes - flooding - contamination of water systems and soil.

outbreaks occur when two or more people become ill after shared exposures in the community.

what are the recomendations on outbreak investigations? - in a community - if a single patient is identified with legionella - who did not leave the facility or campus for the 10 days prior to the onset. - if in a health care facility - if there are at least two possible legionella patients who spent any time in the hospital or long term facility with in the 12 months of each other.

the engineered water systems are a major source of the infection because, they are maintained at a temperature that prevent scalding but also is ideal for legionella growth.

among the spectrum of sporadic to common source out breaks- premise plumbing is associated with mostly sporadic cases where as water features are associated with outbreaks.

• buildings with inconsistant use pattern are assosiated with outbreaks.

sporadic cases: - identification of the source is difficult because the spectrum of water exposures is broad and incubation periods can be long. - studies show that 5-30% of house hold domestic hot water samples have legionella spp.

risk factors: - old age >40 years<br /> - males 3X > over females - smoking - causes anatomic changes in the respiratory epithelium, impairs neutrophills and monocyte phagocytosis and has negative effect on the airway ciliary clearance.

*smoking is a dose dependant risk factor.

• cannabiis is also associated with increased risk.
• COPD.
• emphysema
• renal disease.
• hepatic disease.
• non smoking pulmonary disease.
• cardiac disease.
• cancer.
• HSCT.
• SOT.
• prednisolone and other GC.
• esp the combination of multiple immunosuppressives put the patients at more risk - these pts are more prone for non pneumophilia and non serogroup 1 infections.

• patients with autoimmune diseases on TNF inhibitors ± GC.

• transmission in lung transplant pts from donor is also recognised.

transmission - usually waterborne. - if high conc - can spread by inhalation and aspiration. - for deposition into alveoli particle should be <10 microns. - infective dose depends on the host. - strain virulence decides the outbreak potential. - estimated attack rates: for pneumonia ~5%, for pontiac fever >90%. - human to human is uncommon, only a single presumptive case is reported. - incubation period: ~2 to 10 days for pneumonia and 24-48 hours for pontiac fever.

• aerobic
• gram negative
• most commmon clinical disease is by - Leigionella pneumophilia serotype 1
• primary habitat - amoeba and free living protozoa.
• humans are accidental hosts.
• biphasic lifestyle : in nutrient rich environment they have a replicative lifestyle and in resource scarce setting they have non infective transmissive phase.
• they enter the protozoa through phagocytosis.
• in premise plumbing systems - the conditions are optimum for growth in the protozoa - where they replicate to concentrations sufficient enough to cause human disease.
• humans acquire the infection through inhalation and aspiration of small aerosolized particles.
• after entering the human they attach to immune cells - phagocytozed - evade intracellular defences and replicate in the human alveolar macrophages and monocytes.

how do they evade the host defences? - legionella containing vaccoules - down regulation of the cytokine receptors. - inhibit the host protein synthesis - avoid lysosomal degradation.

are there any innate immune components that can target the organism? - yes. - pattern recognising receptors. - toll like receptors. - nucleotide binding oligomerization domain like receptors.

there receptors activate the adaptive CD4 and CD8 cytotoxic T cells which produce: - INF gamma - TNF

this promotes: - the neutrophilic recruitment into the lung - proinflammatory responses.

this cascade is like a double edged sword. it can clear the pathogen and at the same time is associated with severe disease.

primarily two diseases 1. legionella pneumonia 2. pontiac fever - primarily linked to water borne exposures.

risk factors: - old age - primary organ dysfunction - immunocompromise - chronic illness.