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Quantifying Individual-Level Inaccuracy in Glomerular Filtration Rate Estimation: A Cross-Sectional Study: Annals of Internal Medicine: Vol 175, No 8

Background: Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown. Objective: To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs. Design: Cross-sectional study. Setting: Four U.S. community-based epidemiologic cohort studies with mGFR. Patients: 3223 participants in 4 studies. Measurements: The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRCR) and with cystatin C. All GFR results are presented as mL/min/1.73 m2. Results: The participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRCR were small; the median difference (mGFR − eGFR) was −0.6 (95% CI, −1.2 to −0.2); however, the individual-level differences were large. At an eGFRCR of 60, 50% of mGFRs ranged from 52 to 67, 80% from 45 to 76, and 95% from 36 to 87. At an eGFRCR of 30, 50% of mGFRs ranged from 27 to 38, 80% from 23 to 44, and 95% from 17 to 54. Substantial disagreement in chronic kidney disease staging by mGFR and eGFRCR was present. Among those with eGFRCR of 45 to 59, 36% had mGFR greater than 60 whereas 20% had mGFR less than 45; among those with eGFRCR of 15 to 29, 30% had mGFR greater than 30 and 5% had mGFR less than 15. The eGFR based on cystatin C did not provide substantial improvement. Limitation: Single measurement of mGFR and serum markers without short-term replicates Conclusion: A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement. Primary Funding Source: National Institutes of Health.

Maternal, Infant, and Child Health Outcomes Associated With the Special Supplemental Nutrition Program for Women, Infants, and Children: A Systematic Review: Annals of Internal Medicine: Vol 175, No 10

Background: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is intended to improve maternal and child health outcomes. In 2009, the WIC food package changed to better align with national nutrition recommendations. Purpose: To determine whether WIC participation was associated with improved maternal, neonatal–birth, and infant–child health outcomes or differences in outcomes by subgroups and WIC enrollment duration. Data Sources: Search (January 2009 to April 2022) included PubMed, Embase, CINAHL, ERIC, Scopus, PsycInfo, and the Cochrane Central Register of Controlled Trials. Study Selection: Included studies had a comparator of WIC-eligible nonparticipants or comparison before and after the 2009 food package change. Data Extraction: Paired team members independently screened articles for inclusion and evaluated risk of bias. Data Synthesis: We identified 20 observational studies. We found: moderate strength of evidence (SOE) that maternal WIC participation during pregnancy is likely associated with lower risk for preterm birth, low birthweight infants, and infant mortality; low SOE that maternal WIC participation may be associated with a lower likelihood of inadequate gestational weight gain, as well as increased well-child visits and childhood immunizations; and low SOE that child WIC participation may be associated with increased childhood immunizations. We found low SOE for differences in some outcomes by race and ethnicity but insufficient evidence for differences by WIC enrollment duration. We found insufficient evidence related to maternal morbidity and mortality outcomes. Limitation: Data are from observational studies with high potential for selection bias related to the choice to participate in WIC, and participation status was self-reported in most studies. Conclusion: Participation in WIC was likely associated with improved birth outcomes and lower infant mortality, and also may be associated with increased child preventive service receipt. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020222452)

Tea Consumption and All-Cause and Cause-Specific Mortality in the UK Biobank: A Prospective Cohort Study: Annals of Internal Medicine: Vol 175, No 9

Background: Tea is frequently consumed worldwide, but the association of tea drinking with mortality risk remains inconclusive in populations where black tea is the main type consumed. Objective: To evaluate the associations of tea consumption with all-cause and cause-specific mortality and potential effect modification by genetic variation in caffeine metabolism. Design: Prospective cohort study. Setting: The UK Biobank. Participants: 498 043 men and women aged 40 to 69 years who completed the baseline touchscreen questionnaire from 2006 to 2010. Measurements: Self-reported tea intake and mortality from all causes and leading causes of death, including cancer, all cardiovascular disease (CVD), ischemic heart disease, stroke, and respiratory disease. Results: During a median follow-up of 11.2 years, higher tea intake was modestly associated with lower all-cause mortality risk among those who drank 2 or more cups per day. Relative to no tea drinking, the hazard ratios (95% CIs) for participants drinking 1 or fewer, 2 to 3, 4 to 5, 6 to 7, 8 to 9, and 10 or more cups per day were 0.95 (95% CI, 0.91 to 1.00), 0.87 (CI, 0.84 to 0.91), 0.88 (CI, 0.84 to 0.91), 0.88 (CI, 0.84 to 0.92), 0.91 (CI, 0.86 to 0.97), and 0.89 (CI, 0.84 to 0.95), respectively. The association was most consistent for those who drank tea without added sugar or added milk to their tea. Inverse associations were seen for mortality from all CVD, ischemic heart disease, and stroke. Findings were similar regardless of whether participants also drank coffee or not or of genetic score for caffeine metabolism. Limitation: Potentially important aspects of tea intake (for example, portion size and tea strength) were not assessed. Conclusion: Higher tea intake was associated with lower mortality risk among those drinking 2 or more cups per day, regardless of genetic variation in caffeine metabolism. These findings suggest that tea, even at higher levels of intake, can be part of a healthy diet. Primary Funding Source: National Cancer Institute Intramural Research Program.

When and How Would You Screen This Patient for Cervical Cancer?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 175, No 2

Successful screening programs based on cervical cytology have dramatically reduced the incidence of cervical cancer in the United States. Human papillomavirus immunization is poised to reduce it further as an increasing percentage of vaccinated women reach adulthood. A recent guideline from the American Cancer Society advises that cervical cancer screening begin at age 25 and that high-risk human papillomavirus testing is the preferred screening test. The U.S. Preventive Services Task Force recommends screening begin at age 21 and that cytology remain incorporated into screening. Here, 2 experts debate how to apply these guidelines to Ms. L, a 22-year-old woman who has never undergone cervical cancer screening.

Reinfection and Risk Behaviors After Treatment of Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy: A Cohort Study: Annals of Internal Medicine: Vol 175, No 9

Background: Hepatitis C virus (HCV) reinfection after successful treatment may reduce the benefits of cure among people who inject drugs. Objective: To evaluate the rate of HCV reinfection for 3 years after successful treatment among people receiving opioid agonist therapy (OAT). Design: A 3-year, long-term, extension study of persons enrolled in the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) study (ClinicalTrials.gov: NCT02105688). Setting: 55 clinical trial sites in 13 countries. Patients: Aged 18 years and older with chronic HCV infection with genotypes 1, 4, or 6 receiving stable OAT. Intervention: No treatments were administered. Measurements: Serum samples were assessed for HCV reinfection. Urine drug screening was performed. Results: Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. The rate of HCV reinfection was 1.7 [95% CI, 0.8 to 3.0] per 100 person-years; 604 person-years of follow-up). A higher rate of reinfection was seen among people with recent injecting drug use (1.9 [95% CI, 0.5 to 4.8] per 100 person-years; 212 person-years). Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up. Limitations: Participants were required to be 80% adherent to OAT at baseline and may represent a population with higher stability and lower risk for HCV reinfection. Rate of reinfection may be underestimated because all participants did not continue in the long-term extension study; whether participants who discontinued were at higher risk for reinfection is unknown. Conclusion: Reinfection with HCV was low but was highest in the first 24 weeks after treatment completion and among people with ongoing injecting drug use and needle–syringe sharing. Primary Funding Source: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

How Would You Manage This Male Patient With Hypogonadism?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 174, No 8

Male hypogonadism is defined as an abnormally low serum testosterone concentration or sperm count. As men age, often in the context of obesity and other comorbid conditions, serum testosterone levels may decrease. Normalizing serum testosterone levels in male adults with hypogonadism may improve symptoms related to androgen deficiency, but controversies exist regarding the long-term benefits and risks of hormone supplementation in this setting. In 2020, the American College of Physicians published a clinical guideline for the use of testosterone supplementation in adult men based on a systematic review of available evidence. Among their recommendations were that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function and not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition. Here, two clinicians with expertise in this area, one a generalist and the other an endocrinologist, debate the management of a patient with sexual symptoms and a low serum testosterone level. They discuss the diagnosis of male hypogonadism, the indications for testosterone therapy, its potential benefits and risks, how it should be monitored, and how long it should be continued.

Evaluation and Management After Acute Left-Sided Colonic Diverticulitis: A Systematic Review: Annals of Internal Medicine: Vol 175, No 3

Background: The value of interventions used after acute colonic diverticulitis is unclear. Purpose: To evaluate postdiverticulitis colonoscopy and interventions to prevent recurrent diverticulitis. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. Study Selection: Comparative studies of interventions of interest reporting critical or important outcomes, and larger single-group studies to evaluate prevalence of colonoscopy findings and harms. Data Extraction: 6 researchers extracted study data and risk of bias. The team assessed strength of evidence. Data Synthesis: 19 studies evaluated colonoscopy. Risk for prevalent colorectal cancer (CRC) compared with the general population is unclear. Based on low-strength evidence, long-term CRC diagnosis is similar with or without colonoscopy. High-strength evidence indicates that risk for prevalent CRC is higher among patients with complicated diverticulitis and colonoscopy complications are rare. Based on high-strength evidence, mesalamine does not reduce recurrence risk (6 randomized controlled trials [RCTs]). Evidence on other nonsurgical interventions is insufficient. For patients with prior complicated or smoldering or frequently recurrent diverticulitis, elective surgery is associated with reduced recurrence (3 studies; high strength). In 19 studies, serious surgical complications were uncommon. Limitations: Few RCTs provided evidence. Heterogeneity of treatment effect was not adequately assessed. Conclusion: It is unclear whether patients with recent acute diverticulitis are at increased risk for prevalent CRC, but those with complicated diverticulitis are at increased risk. Mesalamine is ineffective in preventing recurrence; other nonsurgical treatments have inadequate evidence. Elective surgery reduces recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most. Primary Funding Source: Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246)

Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care: A Randomized, Controlled, Multicenter Trial: Annals of Internal Medicine: Vol 174, No 9

Background: Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. Objective: To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. Design: Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987) Setting: 3 Swiss teaching hospitals. Patients: Adult medical patients who were hospitalized. Intervention: Patients were randomly assigned to bedside or outside the room case presentation. Measurements: The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. Results: Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, −2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, −2.31 minutes [CI, −2.98 to −1.63 minutes]; P < 0.001). Limitation: Only Swiss hospitals and medical patients were included. Conclusion: Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. Primary Funding Source: Swiss National Foundation (10531C_ 182422).

Effect of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the United States: A Simulation Modeling Approach: Annals of Internal Medicine: Vol 174, No 1

Background: Across the United States, various social distancing measures were implemented to control the spread of coronavirus disease 2019 (COVID-19). However, the effectiveness of such measures for specific regions with varying population demographic characteristics and different levels of adherence to social distancing is uncertain. Objective: To determine the effect of social distancing measures in unique regions. Design: An agent-based simulation model. Setting: Agent-based model applied to Dane County, Wisconsin; the Milwaukee metropolitan (metro) area; and New York City (NYC). Patients: Synthetic population at different ages. Intervention: Different times for implementing and easing social distancing measures at different levels of adherence. Measurements: The model represented the social network and interactions among persons in a region, considering population demographic characteristics, limited testing availability, “imported” infections, asymptomatic disease transmission, and age-specific adherence to social distancing measures. The primary outcome was the total number of confirmed COVID-19 cases. Results: The timing of and adherence to social distancing had a major effect on COVID-19 occurrence. In NYC, implementing social distancing measures 1 week earlier would have reduced the total number of confirmed cases from 203 261 to 41 366 as of 31 May 2020, whereas a 1-week delay could have increased the number of confirmed cases to 1 407 600. A delay in implementation had a differential effect on the number of cases in the Milwaukee metro area versus Dane County, indicating that the effect of social distancing measures varies even within the same state. Limitation: The effect of weather conditions on transmission dynamics was not considered. Conclusion: The timing of implementing and easing social distancing measures has major effects on the number of COVID-19 cases. Primary Funding Source: National Institute of Allergy and Infectious Diseases.

Should You Recommend Inhaled Corticosteroids for This Patient With Chronic Obstructive Pulmonary Disease?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 172, No 11

Approximately 12 million adults in the United States receive a diagnosis of chronic obstructive pulmonary disease (COPD) each year, and it is the fourth leading cause of death. Chronic obstructive pulmonary disease refers to a group of diseases that cause airflow obstruction and a constellation of symptoms, including cough, sputum production, and shortness of breath. The main risk factor for COPD is tobacco smoke, but other environmental exposures also may contribute. The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2020 Report aims to provide a nonbiased review of the current evidence for the assessment, diagnosis, and treatment of patients with COPD. To date, no conclusive evidence exists that any existing medications for COPD modify mortality. The mainstay of treatment for COPD is inhaled bronchodilators, whereas the role of inhaled corticosteroids is less clear. Inhaled corticosteroids have substantial risks, including an increased risk for pneumonia. Here, 2 experts, both pulmonologists, reflect on the care of a woman with severe COPD, a 50–pack-year smoking history, frequent COPD exacerbations, and recurrent pneumonia. They consider the indications for inhaled corticosteroids in COPD, when inhaled corticosteroids should be withdrawn, and what other treatments are available.

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