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Blood Pressure Effect of Traffic-Related Air Pollution: A Crossover Trial of In-Vehicle Filtration: Annals of Internal Medicine: Vol 176, No 12

Background: Ambient air pollution, including traffic-related air pollution (TRAP), increases cardiovascular disease risk, possibly through vascular alterations. Limited information exists about in-vehicle TRAP exposure and vascular changes. Objective: To determine via particle filtration the effect of on-roadway TRAP exposure on blood pressure and retinal vasculature. Design: Randomized crossover trial. (ClinicalTrials.gov: NCT05454930) Setting: In-vehicle scripted commutes driven through traffic in Seattle, Washington, during 2014 to 2016. Participants: Normotensive persons aged 22 to 45 years (n = 16). Intervention: On 2 days, on-road air was entrained into the vehicle. On another day, the vehicle was equipped with high-efficiency particulate air (HEPA) filtration. Participants were blinded to the exposure and were randomly assigned to the sequence. Measurements: Fourteen 3-minute periods of blood pressure were recorded before, during, and up to 24 hours after a drive. Image-based central retinal arteriolar equivalents (CRAEs) were measured before and after. Brachial artery diameter and gene expression were also measured and will be reported separately. Results: Mean age was 29.7 years, predrive systolic blood pressure was 122.7 mm Hg, predrive diastolic blood pressure was 70.8 mm Hg, and drive duration was 122.3 minutes (IQR, 4 minutes). Filtration reduced particle count by 86%. Among persons with complete data (n = 13), at 1 hour, mean diastolic blood pressure, adjusted for predrive levels, order, and carryover, was 4.7 mm Hg higher (95% CI, 0.9 to 8.4 mm Hg) for unfiltered drives compared with filtered drives, and mean adjusted systolic blood pressure was 4.5 mm Hg higher (CI, −1.2 to 10.2 mm Hg). At 24 hours, adjusted mean diastolic blood pressure (unfiltered) was 3.8 mm Hg higher (CI, 0.02 to 7.5 mm Hg) and adjusted mean systolic blood pressure was 1.1 mm Hg higher (CI, −4.6 to 6.8 mm Hg). Adjusted mean CRAE (unfiltered) was 2.7 μm wider (CI, −1.5 to 6.8 μm). Limitations: Imprecise estimates due to small sample size; seasonal imbalance by exposure order. Conclusion: Filtration of TRAP may mitigate its adverse effects on blood pressure rapidly and at 24 hours. Validation is required in larger samples and different settings. Primary Funding Source: U.S. Environmental Protection Agency and National Institutes of Health.

Fatal Drug Overdose Risks of Health Care Workers in the United States: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 176, No 8

Background: Despite an unprecedented increase in drug overdose deaths in the United States, the risks faced by U.S. health care workers, who often have access to controlled prescription drugs, are not known. Objective: To estimate risks for drug overdose death among health care workers relative to non–health care workers. Design: Prospective cohort study. Setting: United States. Participants: Health care workers (n = 176 000) and non–health care workers (n = 1 662 000) aged 26 years or older surveyed in 2008 and followed for cause of death through 2019. Measurements: Age- and sex-standardized drug overdose deaths were determined for 6 health care worker groups (physicians, registered nurses, other treating or diagnosing health care workers, health technicians, health care support workers, and social or behavioral health workers) and non–health care workers. Adjusted drug overdose death hazards (and 95% CIs) were also evaluated, with adjustment for age, sex, race/ethnicity, marital status, education, income, urban or rural residence, and region. Results: Approximately 0.07% of our study sample died of a drug overdose during follow-up. Among health care workers, annual standardized rates of drug overdose death per 100 000 persons ranged from 2.3 (95% CI, 0 to 4.8) for physicians to 15.5 (CI, 9.8 to 21.2) for social or behavioral health workers. Compared with those for non–health care workers, the adjusted hazards of total drug overdose death were significantly increased for social or behavioral health workers (adjusted hazard ratio, 2.55 [CI, 1.74 to 3.73]), registered nurses (adjusted hazard ratio, 2.22 [CI, 1.57 to 3.13]), and health care support workers (adjusted hazard ratio, 1.60 [CI, 1.19 to 2.16]), but not for physicians (adjusted hazard ratio, 0.61 [CI, 0.19 to 1.93]), other treating or diagnosing health care workers (adjusted hazard ratio, 0.93 [CI, 0.44 to 1.95]), or health technicians (adjusted hazard ratio, 1.13 [CI, 0.75 to 1.68]). Results were generally similar for opioid-related overdose deaths and unintentional overdose deaths. Limitation: Unmeasured confounding, uncertain validity of cause of death, and one-time assessment of occupation. Conclusion: Registered nurses, social or behavioral health workers, and health care support workers were at increased risk for drug overdose death, suggesting the need to identify and intervene on those at high risk. Primary Funding Source: National Heart, Lung, and Blood Institute.

Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 177, No 2

Background: North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. Objective: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. Design: Time-conditional propensity score–matched, new-user cohort study. Setting: Health insurance databases from the Régie de l’assurance maladie du Québec in Canada. Patients: Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. Measurements: The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. Results: The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). Limitation: Residual confounding, including from lack of smoking information. Conclusion: In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. Primary Funding Source: Canadian Institutes of Health Research and Canadian Lung Association.

Association Between Vascular 18F-Fluorodeoxyglucose Uptake at Diagnosis and Change in Aortic Dimensions in Giant Cell Arteritis: A Cohort Study: Annals of Internal Medicine: Vol 176, No 10

Background: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular 18F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications. Objective: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions. Design: Prospective cohort study. Setting: University Hospitals Leuven. Patients: 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids. Measurements: Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope. Results: When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]). Limitation: The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines. Conclusion: Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation. Primary Funding Source: None.

Incidence of and Factors Associated With Recurrent Firearm Injury Among Patients Presenting to St. Louis Trauma Centers, 2010 to 2019: A Cohort Study: Annals of Internal Medicine: Vol 176, No 9

Background: Firearm injuries are a public health crisis in the United States. Objective: To examine the incidence and factors associated with recurrent firearm injuries and death among patients presenting with an acute (index), nonfatal firearm injury. Design: Multicenter, observational, cohort study. Setting: Four adult and pediatric level I trauma hospitals in St. Louis, Missouri, 2010 to 2019. Participants: Consecutive adult and pediatric patients (n = 9553) presenting to a participating hospital with a nonfatal acute firearm injury. Measurements: Data on firearm-injured patient demographics, hospital and diagnostic information, health insurance status, and death were collected from the St. Louis Region-Wide Hospital-Based Violence Intervention Program Data Repository. The Centers for Disease Control and Prevention (CDC) Social Vulnerability Index was used to characterize the social vulnerability of the census tracts of patients’ residences. Analysis included descriptive statistics and time-to-event analyses estimating the probability of experiencing a recurrent firearm injury. Results: We identified 10 293 acutely firearm-injured patients of whom 9553 survived the injury and comprised the analytic sample. Over a median follow-up of 3.5 years (IQR, 1.5 to 6.4 years), 1155 patients experienced a recurrent firearm injury including 5 firearm suicides and 149 fatal firearm injuries. Persons experiencing recurrent firearm injury were young (25.3 ± 9.5 years), predominantly male (93%), Black (96%), and uninsured (50%), and resided in high social vulnerability regions (65%). The estimated risk for firearm reinjury was 7% at 1 year and 17% at 8 years. Limitations: Limited data on comorbidities and patient-level social determinants of health. Inability to account for recurrent injuries presenting to nonstudy hospitals. Conclusion: Recurrent injury and death are frequent among survivors of firearm injury, particularly among patients from socially vulnerable areas. Our findings highlight the need for interventions to prevent recurrence. Primary Funding Source: Emergency Medicine Foundation–AFFIRM and Missouri Foundation for Health.

Comparison of Hospital Outcomes for Patients Treated by Allopathic Versus Osteopathic Hospitalists: An Observational Study: Annals of Internal Medicine: Vol 176, No 6

Background: The United States has 2 types of degree programs that educate physicians: allopathic and osteopathic medical schools. Objective: To determine whether quality and costs of care differ between hospitalized Medicare patients treated by allopathic or osteopathic physicians. Design: Retrospective observational study. Setting: Medicare claims data. Patients: 20% random sample of Medicare fee-for-service beneficiaries hospitalized with a medical condition during 2016 to 2019 and treated by hospitalists. Measurements: The primary outcome was 30-day patient mortality. The secondary outcomes were 30-day readmission, length of stay (LOS), and health care spending (Part B spending). Multivariable regression models adjusted for patient and physician characteristics and their hospital-level averages (to effectively estimate differences within hospitals) were estimated. Results: Of 329 510 Medicare admissions, 253 670 (77.0%) and 75 840 (23.0%) received care from allopathic and osteopathic physicians, respectively. The results can rule out important differences in quality and costs of care between allopathic versus osteopathic physicians for patient mortality (adjusted mortality, 9.4% for allopathic physicians vs. 9.5% [reference] for osteopathic hospitalists; average marginal effect [AME], −0.1 percentage point [95% CI, −0.4 to 0.1 percentage point]; P = 0.36), readmission (15.7% vs. 15.6%; AME, 0.1 percentage point [CI, −0.4 to 0.3 percentage point; P = 0.72), LOS (4.5 vs. 4.5 days; adjusted difference, −0.001 day [CI, −0.04 to 0.04 day]; P = 0.96), and health care spending ($1004 vs. $1003; adjusted difference, $1 [CI, −$8 to $10]; P = 0.85). Limitation: Data were limited to elderly Medicare patients hospitalized with medical conditions. Conclusion: The quality and costs of care were similar between allopathic and osteopathic hospitalists when they cared for elderly patients and worked as the principal physician in a team of health care professionals that often included other allopathic and osteopathic physicians. Primary Funding Source: National Institutes of Health/National Institute on Aging.

Relationship Between Clinician Language and the Success of Behavioral Weight Loss Interventions: A Mixed-Methods Cohort Study: Annals of Internal Medicine: Vol 176, No 11

Background: International guidelines recommend that primary care clinicians recognize obesity and offer treatment opportunistically, but there is little evidence on how clinicians can discuss weight and offer treatment in ways that are well received and effective. Objective: To examine relationships between language used in the clinical visit and patient weight loss. Design: Mixed-methods cohort study. Setting: 38 primary care clinics in England participating in the Brief Intervention for Weight Loss trial. Participants: 246 patients with obesity seen by 87 general practitioners randomly sampled from the intervention group of the randomized clinical trial. Measurements: Conversation analysis of recorded discussions between 246 patients with obesity and 87 clinicians regarding referral to a 12-week behavioral weight management program offered as part of the randomized clinical trial. Clinicians’ interactional approaches were identified and their association with patient weight loss at 12 months (primary outcome) was examined. Secondary outcomes included patients’ agreement to attend weight management, attendance, loss of 5% body weight, actions taken to lose weight, and postvisit satisfaction. Results: Three interactional approaches were identified on the basis of clinicians’ linguistic and paralinguistic practices: creating a sense of referrals as “good news” related to the opportunity of the referral (n = 62); “bad news,” focusing on the harms of obesity (n = 82); or neutral (n = 102). Outcome data were missing from 57 participants, so weighted analyses were done to adjust for missingness. Relative to neutral news, good news was associated with increased agreement to attend the program (adjusted risk difference, 0.25 [95% CI, 0.15 to 0.35]), increased attendance (adjusted risk difference, 0.45 [CI, 0.34 to 0.56]), and weight change (adjusted difference, −3.60 [CI, −6.58 to −0.62]). There was no evidence of differences in mean weight change comparing bad and neutral news, and no evidence of differences in patient satisfaction across all 3 approaches. Limitations: Data were audio only, so body language and nonverbal cues could not be assessed. There is potential for selection bias and residual confounding. Conclusion: When raising the topic of excess weight in clinical visits, presenting weight loss treatment as a positive opportunity is associated with greater uptake of treatment and greater weight loss. Primary Funding Source: National Institute for Health and Care Research School for Primary Care Research and the Foundation for the Sociology of Health and Illness.

Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 176, No 1

Background: It remains unclear if a low-carbohydrate, high-fat (LCHF) diet is a possible treatment strategy for type 2 diabetes mellitus (T2DM), and the effect on nonalcoholic fatty liver disease (NAFLD) has not been investigated. Objective: To investigate the effect of a calorie-unrestricted LCHF diet, with no intention of weight loss, on T2DM and NAFLD compared with a high-carbohydrate, low-fat (HCLF) diet. Design: 6-month randomized controlled trial with a 3-month follow-up. (ClinicalTrials.gov: NCT03068078) Setting: Odense University Hospital in Denmark from November 2016 until June 2020. Participants: 165 participants with T2DM. Intervention: Two calorie-unrestricted diets: LCHF diet with 50 to 60 energy percent (E%) fat, less than 20E% carbohydrates, and 25E% to 30E% proteins and HCLF diet with 50E% to 60E% carbohydrates, 20E% to 30E% fats, and 20E% to 25E% proteins. Measurements: Glycemic control, serum lipid levels, metabolic markers, and liver biopsies to assess NAFLD. Results: The mean age was 56 years (SD, 10), and 58% were women. Compared with the HCLF diet, participants on the LCHF diet had greater improvements in hemoglobin A1c (mean difference in change, −6.1 mmol/mol [95% CI, −9.2 to −3.0 mmol/mol] or −0.59% [CI, −0.87% to −0.30%]) and lost more weight (mean difference in change, −3.8 kg [CI, −6.2 to −1.4 kg]). Both groups had higher high-density lipoprotein cholesterol and lower triglycerides at 6 months. Changes in low-density lipoprotein cholesterol were less favorable in the LCHF diet group than in the HCLF diet group (mean difference in change, 0.37 mmol/L [CI, 0.17 to 0.58 mmol/L] or 14.3 mg/dL [CI, 6.6 to 22.4 mg/dL]). No statistically significant between-group changes were detected in the assessment of NAFLD. Changes were not sustained at the 9-month follow-up. Limitation: Open-label trial, self-reported adherence, unintended weight loss, and lack of adjustment for multiple comparisons. Conclusion: Persons with T2DM on a 6-month, calorie-unrestricted, LCHF diet had greater clinically meaningful improvements in glycemic control and weight compared with those on an HCLF diet, but the changes were not sustained 3 months after intervention. Primary Funding Source: Novo Nordisk Foundation.

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)

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