Most Popular Articles

Most Popular Articles List

  • Evaluation and Treatment of Knee Pain

    A Review
    JAMA. October 24/31, 2023: 330(16):1568-1580

    Importance

    Approximately 5% of all primary care visits in adults are related to knee pain. Osteoarthritis (OA), patellofemoral pain, and meniscal tears are among the most common causes of knee pain.

    Observations

    Knee OA, affecting an estimated 654 million people worldwide, is the most likely diagnosis of knee pain in patients aged 45 years or older who present with activity-related knee joint pain with no or less than 30 minutes of morning stiffness (95% sensitivity; 69% specificity). Patellofemoral pain typically affects people younger than 40 years who are physically active and has a lifetime prevalence of approximately 25%. The presence of anterior knee pain during a squat is approximately 91% sensitive and 50% specific for patellofemoral pain. Meniscal tears affect an estimated 12% of the adult population and can occur following acute trauma (eg, twisting injury) in people younger than 40 years. Alternatively, a meniscal tear may be a degenerative condition present in patients with knee OA who are aged 40 years or older. The McMurray test, consisting of concurrent knee rotation (internal or external to test lateral or medial meniscus, respectively) and extension (61% sensitivity; 84% specificity), and joint line tenderness (83% sensitivity; 83% specificity) assist diagnosis of meniscal tears. Radiographic imaging of all patients with possible knee OA is not recommended. First-line management of OA comprises exercise therapy, weight loss (if overweight), education, and self-management programs to empower patients to better manage their condition. Surgical referral for knee joint replacement can be considered for patients with end-stage OA (ie, no or minimal joint space with inability to cope with pain) after using all appropriate conservative options. For patellofemoral pain, hip and knee strengthening exercises in combination with foot orthoses or patellar taping are recommended, with no indication for surgery. Conservative management (exercise therapy for 4-6 weeks) is also appropriate for most meniscal tears. For severe traumatic (eg, bucket-handle) tears, consisting of displaced meniscal tissue, surgery is likely required. For degenerative meniscal tears, exercise therapy is first-line treatment; surgery is not indicated even in the presence of mechanical symptoms (eg, locking, catching).

    Conclusions and Relevance

    Knee OA, patellofemoral pain, and meniscal tears are common causes of knee pain, can be diagnosed clinically, and can be associated with significant disability. First-line treatment for each condition consists of conservative management, with a focus on exercise, education, and self-management.

  • A Regional Intervention to Improve the Hospital Mortality Associated With Coronary Artery Bypass Graft Surgery

    JAMA. March 20, 1996: 275(11):841-846

    Objective

    To determine whether an organized intervention including data feedback, training in continuous quality improvement techniques, and site visits to other medical centers could improve the hospital mortality rates associated with coronary artery bypass graft (CABG) surgery.

    Design

    Regional intervention study. Patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected on CABG patients in Northern New England between July 1, 1987, and July 31, 1993.

    Setting

    This study included all 23 cardiothoracic surgeons practicing in Maine, New Hampshire, and Vermont during the study period.

    Patients

    Data were collected on 15095 consecutive patients undergoing isolated CABG procedures in Maine, New Hampshire, and Vermont during the study period.

    Interventions

    A three-component intervention aimed at reducing CABG mortality was fielded in 1990 and 1991. The interventions included feedback of outcome data, training in continuous quality improvement techniques, and site visits to other medical centers.

    Main Outcome Measure

    A comparison of the observed and expected hospital mortality rates during the postintervention period.

    Results

    During the postintervention period, we observed the outcomes for 6488 consecutive cases of CABG surgery. There were 74 fewer deaths than would have been expected. This 24% reduction in the hospital mortality rate was statistically significant (P=.001). This reduction in mortality rate was relatively consistent across patient subgroups and was temporally associated with the interventions.

    Conclusion

    We conclude that a multi-institutional, regional model for the continuous improvement of surgical care is feasible and effective. This model may have applications in other settings. (JAMA. 1996;275:841-846)

  • Patent Foramen Ovale and Stroke

    A Review
    JAMA. October 28, 2025: 334(16):1463-1473

    Importance

    A patent foramen ovale (PFO), an opening between the right and left atria during normal fetal development that fails to close after birth, is present in approximately 25% of all adults. Paradoxical embolism, a venous thromboembolism that travels to the systemic circulation typically through a PFO, accounts for about 5% of all strokes and 10% of strokes in younger patients.

    Observations

    Approximately 50% of patients 60 years or younger with an embolic stroke of undetermined source (cryptogenic stroke) have a PFO, compared with 25% of the general population. The Risk of Paradoxical Embolism (RoPE) score incorporates clinical characteristics (age, history of stroke or transient ischemic attack, diabetes, hypertension, smoking, cortical infarct on imaging) to predict the likelihood that embolic stroke of undetermined source was caused by a PFO. Among patients in the lowest RoPE score category (score <3), PFO prevalence was similar to that in the general population (23%), while PFO prevalence was 77% in patients with a RoPE score of 9 or 10. The PFO-Associated Stroke Causal Likelihood (PASCAL) classification system combines the RoPE score and anatomical criteria from echocardiography (large shunt, atrial septal aneurysm) to classify PFO as the “probable,” “possible,” or “unlikely” cause of otherwise cryptogenic stroke. PFO closure reduces recurrent ischemic stroke in patients 60 years or younger with cryptogenic stroke. In a pooled analysis of 6 trials (3740 patients), the annualized incidence of stroke over a median follow-up of 57 months was 0.47% (95% CI, 0.35%-0.65%) with PFO closure vs 1.09% (95% CI, 0.88%-1.36%) with medical therapy (adjusted hazard ratio, 0.41 [95% CI, 0.28-0.60]). However, the benefits and harms of closure were highly heterogeneous across the trial populations. In patients categorized as PASCAL “probable” (ie, younger patients without vascular risk factors and high-risk PFO anatomical features), there was a 90% decreased relative rate of recurrent ischemic stroke after PFO closure at 2 years (hazard ratio, 0.10 [95% CI, 0.03-0.35]; absolute risk reduction, 2.1% [95% CI, 0.9%-3.4%]). PASCAL “unlikely” patients (eg, older patients with vascular risk factors and no high-risk PFO anatomical features) did not have a lower recurrent stroke rate with PFO closure but had higher risk of procedure- and device-related adverse events, such as atrial fibrillation.

    Conclusions and Relevance

    Patent foramen ovale is present in approximately 25% of all adults and is a common cause of stroke in young and middle-aged patients. The PASCAL classification system can help guide patient selection for PFO closure. Percutaneous PFO closure substantially reduces the risk of stroke recurrence in well-selected patients younger than 60 years after cryptogenic stroke.

  • Anxiety Disorders

    A Review
    JAMA. December 27, 2022: 328(24):2431-2445

    Importance

    Anxiety disorders have a lifetime prevalence of approximately 34% in the US, are often chronic, and significantly impair quality of life and functioning.

    Observations

    Anxiety disorders are characterized by symptoms that include worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Generalized anxiety disorder (6.2% lifetime prevalence), social anxiety disorder (13% lifetime prevalence), and panic disorder (5.2% lifetime prevalence) with or without agoraphobia are common anxiety disorders seen in primary care. Anxiety disorders are associated with physical symptoms, such as palpitations, shortness of breath, and dizziness. Brief screening measures applied in primary care, such as the Generalized Anxiety Disorder–7, can aid in diagnosis of anxiety disorders (sensitivity, 57.6% to 93.9%; specificity, 61% to 97%). Providing information about symptoms, diagnosis, and evidence-based treatments is a first step in helping patients with anxiety. First-line treatments include pharmacotherapy and psychotherapy. Selective serotonin reuptake inhibitors (SSRIs, eg, sertraline) and serotonin-norepinephrine reuptake inhibitors (SNRIs, eg, venlafaxine extended release) remain first-line pharmacotherapy for generalized anxiety disorder, social anxiety disorder, and panic disorder. Meta-analyses suggest that SSRIs and SNRIs are associated with small to medium effect sizes compared with placebo (eg, generalized anxiety disorder: standardized mean difference [SMD], −0.55 [95% CI, −0.64 to −0.46]; social anxiety disorder: SMD, −0.67 [95% CI, −0.76 to −0.58]; panic disorder: SMD, −0.30 [95% CI, −0.37 to −0.23]). Cognitive behavioral therapy is the psychotherapy with the most evidence of efficacy for anxiety disorders compared with psychological or pill placebo (eg, generalized anxiety disorder: Hedges g = 1.01 [large effect size] [95% CI, 0.44 to 1.57]; social anxiety disorder: Hedges g = 0.41 [small to medium effect] [95% CI, 0.25 to 0.57]; panic disorder: Hedges g = 0.39 [small to medium effect[ [95% CI, 0.12 to 0.65]), including in primary care. When selecting treatment, clinicians should consider patient preference, current and prior treatments, medical and psychiatric comorbid illnesses, age, sex, and reproductive planning, as well as cost and access to care.

    Conclusions and Relevance

    Anxiety disorders affect approximately 34% of adults during their lifetime in the US and are associated with significant distress and impairment. First-line treatments for anxiety disorders include cognitive behavioral therapy, SSRIs such as sertraline, and SNRIs such as venlafaxine extended release.

  • Caregiver Burden

    A Clinical Review
    JAMA. March 12, 2014: 311(10):1052-1060

    IMPORTANCE

    Caregiver burden may result from providing care for patients with chronic illness. It can occur in any of the 43.5 million individuals providing support to midlife and older adults. Caregiver burden is frequently overlooked by clinicians.

    OBJECTIVES

    To outline the epidemiology of caregiver burden; to provide strategies to diagnose, assess, and intervene for caregiver burden in clinical practice; and to evaluate evidence on interventions intended to avert or mitigate caregiver burden and related caregiver distress.

    EVIDENCE

    Cohort studies examining the relation between demographic and social risk factors and adverse outcomes of caregiver burden were reviewed. Review of recent meta-analyses to summarize the effectiveness of caregiver burden interventions were identified by searching Ovid MEDLINE, AgeLine, and the Cochrane Library.

    RESULTS

    Risk factors for caregiver burden include female sex, low educational attainment, residence with the care recipient, higher number of hours spent caregiving, depression, social isolation, financial stress, and lack of choice in being a caregiver. Practical assessment strategies for caregiver burden exist to evaluate caregivers, their care recipients, and the care recipient’s overall caregiving needs. A variety of psychosocial and pharmacological interventions have shown mild to modest efficacy in mitigating caregiver burden and associated manifestations of caregiver distress in high-quality meta-analyses. Psychosocial interventions include support groups or psychoeducational interventions for caregivers of dementia patients (effect size, 0.09-0.23). Pharmacologic interventions include use of anticholinergics or antipsychotic medications for dementia or dementia-related behaviors in the care recipient (effect size, 0.18-0.27). Many studies showed improvements in caregiver burden–associated symptoms (eg, mood, coping, self-efficacy) even when caregiver burden itself was minimally improved.

    CONCLUSIONS AND RELEVANCE

    Physicians have a responsibility to recognize caregiver burden. Caregiver assessment and intervention should be tailored to the individual circumstances and contexts in which caregiver burden occurs.

  • Dalbavancin for Treatment of Staphylococcus aureus Bacteremia

    The DOTS Randomized Clinical Trial
    JAMA. September 9, 2025: 334(10):866-877

    Importance

    Dalbavancin is a long-acting intravenous lipoglycopeptide that may be effective for treatment of complicated Staphylococcus aureus bacteremia without requiring long-term intravenous access.

    Objective

    To evaluate the efficacy and safety of dalbavancin vs standard therapy for completion of treatment of complicated S aureus bacteremia.

    Design, Setting, and Participants

    Open-label, assessor-masked, randomized clinical trial conducted from April 2021 to December 2023 at 23 medical centers in the US (n = 22) and Canada (n = 1). Participant follow-up lasted 70 days (180 days for participants with osteomyelitis); date of final follow-up was December 1, 2023. Hospitalized adults with complicated S aureus bacteremia who achieved blood culture clearance following at least 72 hours but no more than 10 days of initial antibacterial therapy were included. Participants were excluded if they had central nervous system infection, retained infected prosthetic material, left-sided endocarditis, or severe immune compromise.

    Interventions

    Participants were randomly assigned to receive either 2 doses of intravenous dalbavancin (n = 100; 1500 mg on days 1 and 8) or 4 to 8 total weeks of standard intravenous therapy (n = 100; cefazolin or antistaphylococcal penicillin if methicillin susceptible; vancomycin or daptomycin if methicillin resistant).

    Main Outcomes and Measures

    The primary outcome was the desirability of outcome ranking (DOOR) at day 70, which involved 5 components (clinical success, infectious complications, safety complications, mortality, and health-related quality of life) and was assessed for superiority (achieved if the 95% CI for the probability of dalbavancin having a superior DOOR was >50%). Secondary outcomes included clinical efficacy at day 70 (prespecified noninferiority margin of 20%) and safety.

    Results

    Of 200 participants randomized (mean [SD] age, 56 [16.2] years; 62 females [31%]), 167 (84%) survived to day 70 and had an efficacy assessment. Participants without a day 70 efficacy assessment were treated as clinical failures in the analyses. The probability of a more desirable day 70 outcome with dalbavancin vs standard therapy was 47.7% (95% CI, 39.8% to 55.7%). Regarding secondary outcomes, clinical efficacy was documented in 73 of 100 for dalbavancin and 72 of 100 for standard therapy (difference, 1.0% [95% CI, −11.5% to 13.5%]), meeting the noninferiority criterion. Serious adverse events were reported in 40 of 100 participants who received dalbavancin and 34 of 100 participants who received standard therapy; treatment-related adverse events were uncommon in both groups.

    Conclusions and Relevance

    Among adult participants with complicated S aureus bacteremia who achieved blood culture clearance, dalbavancin was not superior to standard therapy by desirability of outcome ranking. When considered with other efficacy and safety outcomes these findings may help inform use of dalbavancin in clinical practice.

    Trial Registration

    ClinicalTrials.gov Identifier: NCT04775953

  • Fluid Therapy for Critically Ill Adults With Sepsis

    A Review
    JAMA. June 13, 2023: 329(22):1967-1980

    Importance

    Approximately 20% to 30% of patients admitted to an intensive care unit have sepsis. While fluid therapy typically begins in the emergency department, intravenous fluids in the intensive care unit are an essential component of therapy for sepsis.

    Observations

    For patients with sepsis, intravenous fluid can increase cardiac output and blood pressure, maintain or increase intravascular fluid volume, and deliver medications. Fluid therapy can be conceptualized as 4 overlapping phases from early illness through resolution of sepsis: resuscitation (rapid fluid administered to restore perfusion); optimization (the risks and benefits of additional fluids to treat shock and ensure organ perfusion are evaluated); stabilization (fluid therapy is used only when there is a signal of fluid responsiveness); and evacuation (excess fluid accumulated during treatment of critical illness is eliminated). Among 3723 patients with sepsis who received 1 to 2 L of fluid, 3 randomized clinical trials (RCTs) reported that goal-directed therapy administering fluid boluses to attain a central venous pressure of 8 to 12 mm Hg, vasopressors to attain a mean arterial blood pressure of 65 to 90 mm Hg, and red blood cell transfusions or inotropes to attain a central venous oxygen saturation of at least 70% did not decrease mortality compared with unstructured clinical care (24.9% vs 25.4%; P = .68). Among 1563 patients with sepsis and hypotension who received 1 L of fluid, an RCT reported that favoring vasopressor treatment did not improve mortality compared with further fluid administration (14.0% vs 14.9%; P = .61). Another RCT reported that among 1554 patients in the intensive care unit with septic shock treated with at least 1 L of fluid compared with more liberal fluid administration, restricting fluid administration in the absence of severe hypoperfusion did not reduce mortality (42.3% vs 42.1%; P = .96). An RCT of 1000 patients with acute respiratory distress during the evacuation phase reported that limiting fluid administration and administering diuretics improved the number of days alive without mechanical ventilation compared with fluid treatment to attain higher intracardiac pressure (14.6 vs 12.1 days; P < .001), and it reported that hydroxyethyl starch significantly increased the incidence of kidney replacement therapy compared with saline (7.0% vs 5.8%; P = .04), Ringer lactate, or Ringer acetate.

    Conclusions and Relevance

    Fluids are an important component of treating patients who are critically ill with sepsis. Although optimal fluid management in patients with sepsis remains uncertain, clinicians should consider the risks and benefits of fluid administration in each phase of critical illness, avoid use of hydroxyethyl starch, and facilitate fluid removal for patients recovering from acute respiratory distress syndrome.

  • Borderline Personality Disorder

    A Review
    JAMA. February 28, 2023: 329(8):670-679

    Importance

    Borderline personality disorder (BPD) affects approximately 0.7% to 2.7% of adults in the US. The disorder is associated with considerable social and vocational impairments and greater use of medical services.

    Observations

    Borderline personality disorder is characterized by sudden shifts in identity, interpersonal relationships, and affect, as well as by impulsive behavior, periodic intense anger, feelings of emptiness, suicidal behavior, self-mutilation, transient, stress-related paranoid ideation, and severe dissociative symptoms (eg, experience of unreality of one’s self or surroundings). Borderline personality disorder is typically diagnosed by a mental health specialist using semistructured interviews. Most people with BPD have coexisting mental disorders such as mood disorders (ie, major depression or bipolar disorder) (83%), anxiety disorders (85%), or substance use disorders (78%). The etiology of BPD is related to both genetic factors and adverse childhood experiences, such as sexual and physical abuse. Psychotherapy is the treatment of choice for BPD. Psychotherapy such as dialectical behavior therapy and psychodynamic therapy reduce symptom severity more than usual care, with medium effect sizes (standardized mean difference) between −0.60 and −0.65. There is no evidence that any psychoactive medication consistently improves core symptoms of BPD. For discrete and severe comorbid mental disorders, eg, major depression, pharmacotherapy such as the selective serotonin reuptake inhibitors escitalopram, sertraline, or fluoxetine may be prescribed. For short-term treatment of acute crisis in BPD, consisting of suicidal behavior or ideation, extreme anxiety, psychotic episodes, or other extreme behavior likely to endanger a patient or others, crisis management is required, which may include prescription of low-potency antipsychotics (eg, quetiapine) or off-label use of sedative antihistamines (eg, promethazine). These drugs are preferred over benzodiazepines such as diazepam or lorazepam.

    Conclusions and Relevance

    Borderline personality disorder affects approximately 0.7% to 2.7% of adults and is associated with functional impairment and greater use of medical services. Psychotherapy with dialectical behavior therapy and psychodynamic therapy are first-line therapies for BPD, while psychoactive medications do not improve the primary symptoms of BPD.

  • Syphilis

    A Review
    JAMA. December 2, 2025: 334(21):1927-1940

    Importance

    Syphilis is an infectious disease caused by Treponema pallidum, a gram-negative, spirochete bacterium. Worldwide, an estimated 8 million adults aged 18 to 49 years acquired syphilis in 2022. From 2019 to 2023, US syphilis cases increased by 61% overall, with diagnoses among females increasing by 112% and congenital syphilis cases increasing by 106%.

    Observations

    Syphilis is transmitted via contact with infectious lesions during vaginal, anal, or oral sex or via the placenta during pregnancy. Individuals at increased risk for syphilis include people with HIV, those engaging in condomless sex with multiple partners, and men who have sex with men (MSM)—who comprised one-third (32.7%) of all males with primary and secondary syphilis in 2023. Early syphilis is defined as syphilis in the first year after infection and includes symptomatic (primary and secondary) and asymptomatic (early latent) stages. Primary syphilis is characterized by painless anogenital lesions. Secondary syphilis is associated with a diffuse rash, mucocutaneous lesions, and lymphadenopathy. Syphilis diagnosed more than a year after infection is referred to as late syphilis and includes asymptomatic (late latent) and symptomatic (tertiary) stages. Neurosyphilis, which can occur at any stage, can lead to meningitis, uveitis, hearing loss, or stroke. In pregnancy, up to 40% of fetuses with in-utero exposure to syphilis are stillborn or die from their infection during infancy. The diagnosis of syphilis relies on serologic reactivity along with a clinical history and presentation consistent with active or latent syphilis infection. The recommended treatment for syphilis is benzathine penicillin G administered as intramuscular doses of 2.4 million units: a single injection for early stage and 3 weekly injections for late latent stage syphilis. Strategies to identify and prevent syphilis infections include (1) screening of sexually active people aged 15 to 44 years at least once and at least annually for those at increased risk, (2) screening 3 times in pregnant individuals (at the first prenatal visit, during the third trimester, and at delivery), (3) counseling about condom use, and (4) offering doxycycline postexposure prophylaxis (200-mg doxycycline taken within 72 hours after sex as postexposure prophylaxis) to MSM and transgender women with a history of a sexually transmitted infection in the past year.

    Conclusions and Relevance

    Syphilis infections, including congenital syphilis, have increased in the US and worldwide over the past decade. First-line treatment for syphilis is benzathine penicillin G. Routine syphilis screening of all pregnant patients and all sexually active people aged 15 to 44 years and use of doxycycline postexposure prophylaxis in individuals at risk for syphilis infection are recommended strategies to decrease syphilis transmission.

  • Intraoperative Driving Pressure–Guided High PEEP vs Standard Low PEEP for Postoperative Pulmonary Complications

    JAMA. February 24, 2026: 335(8):693-702

    Importance

    The effect of individualized high positive end-expiratory pressure (PEEP) and recruitment maneuvers, targeting a low driving pressure, on clinical outcomes in patients undergoing open abdominal surgery is uncertain.

    Objective

    To compare driving pressure–guided high PEEP and recruitment maneuvers with standard low PEEP without recruitment maneuvers with respect to postoperative pulmonary complications.

    Design, Setting, and Participants

    Randomized clinical trial of 1435 adults at increased risk for postoperative pulmonary complications who were scheduled for open abdominal surgery. The trial was conducted at 29 sites in 5 countries across Europe from April 2019 to December 2024; final follow-up was in March 2025. Statistical analysis was conducted in May 2025.

    Intervention

    Patients were randomized to undergo intraoperative ventilation with driving pressure–guided high PEEP and recruitment maneuvers (n = 718) or to intraoperative ventilation with standard low PEEP (n = 717). All patients received low tidal volume ventilation.

    Main Outcomes and Measures

    The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including severe respiratory failure, bronchospasm, suspected pulmonary infection, pulmonary infiltrates, aspiration pneumonitis, atelectasis, acute respiratory distress syndrome, pleural effusion, cardiopulmonary edema, and pneumothorax. Among the 16 prespecified secondary outcomes, 4 concerned intraoperative complications, including hypotension (decrease in mean arterial pressure of >20% for >3 minutes) and desaturation (SpO2 <92% for >1 minute).

    Results

    Among 1468 adults, 1435 (98%) completed the trial (median [IQR] age, 66 [57-74] years; 52% female). In the primary analysis population, the primary outcome occurred in 142 of 718 patients (19.8%) in the driving pressure–guided high PEEP group compared with 125 of 717 patients (17.4%) in the low PEEP group (absolute difference, 2.5% [95% CI, −1.5% to 6.4%]; P = .23). The incidence of hypotension (382 [54.0%] vs 317 [45.0%]) and use of vasoactive agents (224 [32.0%] vs 130 [18.8%]) was higher in the high PEEP group; the incidence of intraoperative desaturation (6 [0.8%] vs 20 [2.8%]) was higher in the low PEEP group.

    Conclusions and Relevance

    Among patients at increased risk for postoperative pulmonary complications undergoing open abdominal surgery under general anesthesia, intraoperative ventilation with driving pressure–guided high PEEP and recruitment maneuvers, compared with a strategy with standard low PEEP, did not reduce postoperative pulmonary complications.

    Trial Registration

    ClinicalTrials.gov Identifier: NCT03884543

  • Thyroid Cancer

    A Review
    JAMA. February 6, 2024: 331(5):425-435

    Importance

    Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer.

    Observations

    Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma.

    Conclusions

    Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.

  • Diagnosis and Management of Headache

    A Review
    JAMA. May 11, 2021: 325(18):1874-1885

    Importance

    Approximately 90% of people in the US experience headache during their lifetime. Migraine is the second leading cause of years lived with disability worldwide.

    Observations

    Primary headache disorders are defined as headaches that are unrelated to an underlying medical condition and are categorized into 4 groups: migraine, tension-type headache, trigeminal autonomic cephalalgias, and other primary headache disorders. Studies evaluating prevalence in more than 100 000 people reported that tension-type headache affected 38% of the population, while migraine affected 12% and was the most disabling. Secondary headache disorders are defined as headaches due to an underlying medical condition and are classified according to whether they are due to vascular, neoplastic, infectious, or intracranial pressure/volume causes. Patients presenting with headache should be evaluated to determine whether their headache is most likely a primary or a secondary headache disorder. They should be evaluated for symptoms or signs that suggest an urgent medical problem such as an abrupt onset, neurologic signs, age 50 years and older, presence of cancer or immunosuppression, and provocation by physical activities or postural changes. Acute migraine treatment includes acetaminophen, nonsteroidal anti-inflammatory drugs, and combination products that include caffeine. Patients not responsive to these treatments may require migraine-specific treatments including triptans (5-HT1B/D agonists), which eliminate pain in 20% to 30% of patients by 2 hours, but are accompanied by adverse effects such as transient flushing, tightness, or tingling in the upper body in 25% of patients. Patients with or at high risk for cardiovascular disease should avoid triptans because of vasoconstrictive properties. Acute treatments with gepants, antagonists to receptors for the inflammatory neuropeptide calcitonin gene–related peptide, such as rimegepant or ubrogepant, can eliminate headache symptoms for 2 hours in 20% of patients but have adverse effects of nausea and dry mouth in 1% to 4% of patients. A 5-HT1F agonist, lasmiditan, is also available for acute migraine treatment and appears safe in patients with cardiovascular risk factors. Preventive treatments include antihypertensives, antiepileptics, antidepressants, calcitonin gene–related peptide monoclonal antibodies, and onabotulinumtoxinA, which reduce migraine by 1 to 3 days per month relative to placebo.

    Conclusions and Relevance

    Headache disorders affect approximately 90% of people during their lifetime. Among primary headache disorders, migraine is most debilitating and can be treated acutely with analgesics, nonsteroidal anti-inflammatory drugs, triptans, gepants, and lasmiditan.

  • Attitudes and Practices of Euthanasia and Physician-Assisted Suicide in the United States, Canada, and Europe

    JAMA. July 5, 2016: 316(1):79-90

    Importance

    The increasing legalization of euthanasia and physician-assisted suicide worldwide makes it important to understand related attitudes and practices.

    Objective

    To review the legal status of euthanasia and physician-assisted suicide and the available data on attitudes and practices.

    Evidence Review

    Polling data and published surveys of the public and physicians, official state and country databases, interview studies with physicians, and death certificate studies (the Netherlands and Belgium) were reviewed for the period 1947 to 2016.

    Findings

    Currently, euthanasia or physician-assisted suicide can be legally practiced in the Netherlands, Belgium, Luxembourg, Colombia, and Canada (Quebec since 2014, nationally as of June 2016). Physician-assisted suicide, excluding euthanasia, is legal in 5 US states (Oregon, Washington, Montana, Vermont, and California) and Switzerland. Public support for euthanasia and physician-assisted suicide in the United States has plateaued since the 1990s (range, 47%-69%). In Western Europe, an increasing and strong public support for euthanasia and physician-assisted suicide has been reported; in Central and Eastern Europe, support is decreasing. In the United States, less than 20% of physicians report having received requests for euthanasia or physician-assisted suicide, and 5% or less have complied. In Oregon and Washington state, less than 1% of licensed physicians write prescriptions for physician-assisted suicide per year. In the Netherlands and Belgium, about half or more of physicians reported ever having received a request; 60% of Dutch physicians have ever granted such requests. Between 0.3% to 4.6% of all deaths are reported as euthanasia or physician-assisted suicide in jurisdictions where they are legal. The frequency of these deaths increased after legalization. More than 70% of cases involved patients with cancer. Typical patients are older, white, and well-educated. Pain is mostly not reported as the primary motivation. A large portion of patients receiving physician-assisted suicide in Oregon and Washington reported being enrolled in hospice or palliative care, as did patients in Belgium. In no jurisdiction was there evidence that vulnerable patients have been receiving euthanasia or physician-assisted suicide at rates higher than those in the general population.

    Conclusions and Relevance

    Euthanasia and physician-assisted suicide are increasingly being legalized, remain relatively rare, and primarily involve patients with cancer. Existing data do not indicate widespread abuse of these practices.

  • Hospital Nurse Staffing and Patient Mortality, Nurse Burnout, and Job Dissatisfaction

    JAMA. October 23/30, 2002: 288(16):1987-1993

    Context

    The worsening hospital nurse shortage and recent California legislation mandating minimum hospital patient-to-nurse ratios demand an understanding of how nurse staffing levels affect patient outcomes and nurse retention in hospital practice.

    Objective

    To determine the association between the patient-to-nurse ratio and patient mortality, failure-to-rescue (deaths following complications) among surgical patients, and factors related to nurse retention.

    Design, Setting, and Participants

    Cross-sectional analyses of linked data from 10 184 staff nurses surveyed, 232 342 general, orthopedic, and vascular surgery patients discharged from the hospital between April 1, 1998, and November 30, 1999, and administrative data from 168 nonfederal adult general hospitals in Pennsylvania.

    Main Outcome Measures

    Risk-adjusted patient mortality and failure-to-rescue within 30 days of admission, and nurse-reported job dissatisfaction and job-related burnout.

    Results

    After adjusting for patient and hospital characteristics (size, teaching status, and technology), each additional patient per nurse was associated with a 7% (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.03–1.12) increase in the likelihood of dying within 30 days of admission and a 7% (OR, 1.07; 95% CI, 1.02–1.11) increase in the odds of failure-to-rescue. After adjusting for nurse and hospital characteristics, each additional patient per nurse was associated with a 23% (OR, 1.23; 95% CI, 1.13–1.34) increase in the odds of burnout and a 15% (OR, 1.15; 95% CI, 1.07–1.25) increase in the odds of job dissatisfaction.

    Conclusions

    In hospitals with high patient-to-nurse ratios, surgical patients experience higher risk-adjusted 30-day mortality and failure-to-rescue rates, and nurses are more likely to experience burnout and job dissatisfaction.

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