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Dementia, according to the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is defined by a significant decline in 1 or more cognitive domains that interferes with a person’s independence in daily activities. Mild cognitive impairment (MCI) differs from dementia in that the impairment is not sufficient to interfere with independence. For the purposes of this discussion, cognitive impairment (CI) includes both dementia and MCI. Various screening tests are available for CI. These tests ask patients to perform a series of tasks that assess 1 or more domains of cognitive function or ask a caregiver to report on the patient’s abilities. A positive result on a screening test does not equate to a diagnosis of CI; rather, it should lead to additional testing to confirm the diagnosis. On review of the evidence, the U.S. Preventive Services Task Force (USPSTF) concluded in 2020 that the evidence was insufficient to assess the balance of benefits and harms of screening for CI in older adults (“I statement”). The USPSTF did clarify that although there is insufficient evidence, there may be important reasons to identify CI. In this article, 2 experts review the available evidence to answer the following questions: What screening tools are available, and how effective are they in identifying patients with CI? What interventions are available for patients found to have CI, to what extent do they improve patient outcomes, and what, if any, negative effects occur? And, would they recommend screening for CI, and why or why not?

Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 177, No 2

Background: Chronic insomnia is common in patients undergoing in-center hemodialysis, yet there is limited evidence on effective treatments for this population. Objective: To compare the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), trazodone, and placebo for insomnia in patients undergoing long-term hemodialysis. Design: Randomized, multicenter, double-blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT03534284) Setting: 26 dialysis units in Albuquerque, New Mexico, and Seattle, Washington. Participants: Patients with Insomnia Severity Index (ISI) score of 10 or greater, with sleep disturbances on 3 or more nights per week for 3 or more months. Intervention: Participants were randomly assigned to 6 weeks of CBT-I, trazodone, or placebo. Measurements: The primary outcome was the ISI score at 7 and 25 weeks from randomization. Results: A total of 923 patients were prescreened, and of the 411 patients with chronic insomnia, 126 were randomly assigned to CBT-I (n = 43), trazodone (n = 42), or placebo (n = 41). The change in ISI scores from baseline to 7 weeks with CBT-I or trazodone was no different from placebo: CBT-I, −3.7 (95% CI, −5.5 to −1.9); trazodone, −4.2 (CI, −5.9 to −2.4); and placebo, −3.1 (CI, −4.9 to −1.3). There was no meaningful change in ISI scores from baseline to 25 weeks: CBT-I, −4.8 (CI, −7.0 to −2.7); trazodone, −4.0 (CI, −6.0 to −1.9); and placebo, −4.3 (CI, −6.4 to −2.2). Serious adverse events (SAEs), particularly serious cardiovascular events, were more frequent with trazodone (annualized cardiovascular SAE incidence rates: CBT-I, 0.05 [CI, 0.00 to 0.29]; trazodone, 0.64 [CI, 0.34 to 1.10]; and placebo, 0.21 [CI, 0.06 to 0.53]). Limitation: Modest sample size and most participants had mild or moderate insomnia. Conclusion: In patients undergoing hemodialysis with mild or moderate chronic insomnia, there was no difference in the effectiveness of 6 weeks of CBT-I or trazodone compared with placebo. The incidence of SAEs was higher with trazodone. Primary Funding Source: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ Clinician

Civility, 1968

The Preacher Lady

Half of What You Learn

On the Pineal Gland

Return to Sender

SARS-CoV-2 Virologic Rebound With Nirmatrelvir–Ritonavir Therapy: An Observational Study: Annals of Internal Medicine: Vol 176, No 12

Background: Data are conflicting regarding an association between treatment of acute COVID-19 with nirmatrelvir−ritonavir (N-R) and virologic rebound (VR). Objective: To compare the frequency of VR in patients with and without N-R treatment for acute COVID-19. Design: Observational cohort study. Setting: Multicenter health care system in Boston, Massachusetts. Participants: Ambulatory adults with acute COVID-19 with and without use of N-R. Intervention: Receipt of 5 days of N-R treatment versus no COVID-19 therapy. Measurements: The primary outcome was VR, defined as either a positive SARS-CoV-2 viral culture result after a prior negative result or 2 consecutive viral loads above 4.0 log10 copies/mL that were also at least 1.0 log10 copies/mL higher than a prior viral load below 4.0 log10 copies/mL. Results: Compared with untreated persons (n = 55), those taking N-R (n = 72) were older, received more COVID-19 vaccinations, and more commonly had immunosuppression. Fifteen participants (20.8%) taking N-R had VR versus 1 (1.8%) who was untreated (absolute difference, 19.0 percentage points [95% CI, 9.0 to 29.0 percentage points]; P = 0.001). All persons with VR had a positive viral culture result after a prior negative result. In multivariable models, only N-R use was associated with VR (adjusted odds ratio, 10.02 [CI, 1.13 to 88.74]; P = 0.038). Virologic rebound was more common among those who started therapy within 2 days of symptom onset (26.3%) than among those who started 2 or more days after symptom onset (0%) (P = 0.030). Among participants receiving N-R, those who had VR had prolonged shedding of replication-competent virus compared with those who did not have VR (median, 14 vs. 3 days). Eight of 16 participants (50% [CI, 25% to 75%]) with VR also reported symptom rebound; 2 were completely asymptomatic. No post-VR resistance mutations were detected. Limitations: Observational study design with differences between the treated and untreated groups; positive viral culture result was used as a surrogate marker for risk for ongoing viral transmission. Conclusion: Virologic rebound occurred in approximately 1 in 5 people taking N-R, often without symptom rebound, and was associated with shedding of replication-competent virus. Primary Funding Source: National Institutes of Health.

Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents

Background: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant’s emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. Design: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. Setting: A national collaboration of pediatric health systems (PEDSnet). Participants: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. Intervention: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. Results: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. Limitation: Observational study design and potentially undocumented infection. Conclusion: This study suggests that BNT162b2 was effective for various COVID-19–related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. Primary Funding Source: National Institutes of Health.

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