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How Would You Manage This Patient With Clostridioides difficile Infection?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 176, No 8

The Infectious Diseases Society of America/Society for Healthcare Epidemiology of America and the American College of Gastroenterology recently released updated guidelines on management of patients with Clostridioides difficile infection. Although these 2 guidelines generally agree, there are a few important differences in their advice to clinicians. In these rounds, 2 experts, an infectious diseases specialist and a gastroenterologist, discuss antibiotic treatment options for nonsevere disease, the role of fecal microbiota transplantation for fulminant disease, and the use of bezlotoxumab to prevent recurrence in the context of Ms. C, a 48-year-old woman with fulminant C difficile infection.

Chronotype, Unhealthy Lifestyle, and Diabetes Risk in Middle-Aged U.S. Women: A Prospective Cohort Study: Annals of Internal Medicine: Vol 176, No 10

Background: Evening chronotype may promote adherence to an unhealthy lifestyle and increase type 2 diabetes risk. Objective: To evaluate the role of modifiable lifestyle behaviors in the association between chronotype and diabetes risk. Design: Prospective cohort study. Setting: Nurses’ Health Study II. Participants: 63 676 nurses aged 45 to 62 years with no history of cancer, cardiovascular disease, or diabetes in 2009 were prospectively followed until 2017. Measurements: Self-reported chronotype using a validated question from the Morningness-Eveningness Questionnaire. The lifestyle behaviors that were measured were diet quality, physical activity, alcohol intake, body mass index (BMI), smoking, and sleep duration. Incident diabetes cases were self-reported and confirmed using a supplementary questionnaire. Results: Participants reporting a “definite evening” chronotype were 54% (95% CI, 49% to 59%) more likely to have an unhealthy lifestyle than participants reporting a “definite morning” chronotype. A total of 1925 diabetes cases were documented over 469 120 person-years of follow-up. Compared with the “definite morning” chronotype, the adjusted hazard ratio (HR) for diabetes was 1.21 (CI, 1.09 to 1.35) for the “intermediate” chronotype and 1.72 (CI, 1.50 to 1.98) for the “definite evening” chronotype after adjustment for sociodemographic factors, shift work, and family history of diabetes. Further adjustment for BMI, physical activity, and diet quality attenuated the association comparing the “definite evening” and “definite morning” chronotypes to 1.31 (CI, 1.13 to 1.50), 1.54 (CI, 1.34 to 1.77), and 1.59 (CI, 1.38 to 1.83), respectively. Accounting for all measured lifestyle and sociodemographic factors resulted in a reduced but still positive association (HR comparing “definite evening” vs. “definite morning” chronotype, 1.19 [CI, 1.03 to 1.37]). Limitations: Chronotype assessment using a single question, self-reported data, and homogeneity of the study population. Conclusion: Middle-aged nurses with an evening chronotype were more likely to report unhealthy lifestyle behaviors and had increased diabetes risk compared with those with a morning chronotype. Accounting for BMI, physical activity, diet, and other modifiable lifestyle factors attenuated much but not all of the increased diabetes risk. Primary Funding Source: National Institutes of Health.

Comparative Effectiveness of Sodium–Glucose Cotransporter-2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and Hospitalizations: A General Population Cohort Study: Annals of Internal Medicine: Vol 176, No 8

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is) decrease serum urate levels, but whether this translates into prevention of recurrent flares among patients with gout and gout-primary emergency department (ED) visits or hospitalizations is unknown. Objective: To compare gout flares and cardiovascular events among patients with gout initiating SGLT2is versus dipeptidyl peptidase 4 inhibitors (DPP-4is), another second-line glucose-lowering agent not associated with serum urate levels or cardiovascular risk. Design: Propensity score–matched, new-user cohort study. Setting: General population database from 1 January 2014 to 30 June 2022. Participants: Patients with gout and type 2 diabetes. Measurements: The primary outcome was recurrent gout flare counts ascertained by ED, hospitalization, outpatient, and medication dispensing records. Secondary outcomes included myocardial infarction and stroke; genital infection (positive control) and osteoarthritis encounter (negative control) were also assessed. Poisson and Cox proportional hazards regressions were used with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis). Results: After propensity score matching, the flare rate was lower among SGLT2i initiators than DPP-4i initiators (52.4 and 79.7 events per 1000 person-years, respectively), with a rate ratio (RR) of 0.66 (95% CI, 0.57 to 0.75) and a rate difference (RD) of −27.4 (CI, −36.0 to −18.7) per 1000 person-years. The corresponding RR and RD for gout-primary ED visits and hospitalizations were 0.52 (CI, 0.32 to 0.84) and −3.4 (CI, −5.8 to −0.9) per 1000 person-years, respectively. The corresponding hazard ratio (HR) and RD for myocardial infarction were 0.69 (CI, 0.54 to 0.88) and −7.6 (CI, −12.4 to −2.8) per 1000 person-years; the HR for stroke was 0.81 (CI, 0.62 to 1.05). Those who initiated SGLT2is showed higher risk for genital infection (HR, 2.15 [CI, 1.39 to 3.30]) and no altered risk for osteoarthritis encounter (HR, 1.07 [CI, 0.95 to 1.20]). Results were similar when propensity score overlap weighting was applied. Limitation: Participants had concurrent type 2 diabetes. Conclusion: Among patients with gout, SGLT2is may reduce recurrent flares and gout-primary ED visits and hospitalizations and may provide cardiovascular benefits. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Modernizing the United States’ Public Health Infrastructure: A Position Paper From the American College of Physicians

The United States’ public health sector plays a crucial role in preventing illness and promoting health. Public health drove massive gains in life expectancy during the 20th century by supporting vaccination campaigns, promoting motor vehicle safety, and preventing and treating tobacco use. However, public health is underfunded and underappreciated, forcing the field to do more with fewer resources. In this position paper, the American College of Physicians (ACP) updates its 2012 policy recommendations on strengthening the nation’s public health infrastructure. ACP calls for effective coordination of public health activities, robust and stable year-to-year funding of public health services, a renewed and well-supported public health workforce, action to address health-related dis- and misinformation, modernized public health data systems, and greater coordination between public health and medical sectors.

Blood Pressure Level in Late Adolescence and Risk for Cardiovascular Events: A Cohort Study: Annals of Internal Medicine: Vol 176, No 10

Background: Not enough is known about the association between blood pressure (BP) in adolescence and future cardiovascular events. Objective: To measure this association using the 2017 American College of Cardiology/American Heart Association guidelines for classifying BP elevation. Design: Cohort study. Setting: Sweden. Participants: Males in late adolescence who were conscripted into the military from 1969 to 1997. Measurements: Baseline BP was measured at conscription. The primary outcome was a composite of cardiovascular death or first hospitalization for myocardial infarction, heart failure, ischemic stroke, or intracerebral hemorrhage. Results: The study included 1 366 519 males with a mean age of 18.3 years. The baseline BP was classified as elevated (120 to 129/<80 mm Hg) for 28.8% of participants and hypertensive (≥130/80 mm Hg) for 53.7%. During a median follow-up of 35.9 years, 79 644 had a primary outcome. The adjusted hazard ratio was 1.10 for elevated BP (95% CI, 1.07 to 1.13), 1.15 for stage 1 isolated systolic hypertension (ISH) (CI, 1.11 to 1.18), 1.23 for stage 1 isolated diastolic hypertension (IDH) (CI, 1.18 to 1.28), 1.32 for stage 1 systolic–diastolic hypertension (SDH) (CI, 1.27 to 1.37), 1.31 for stage 2 ISH (CI, 1.28 to 1.35), 1.55 for stage 2 IDH (CI, 1.42 to 1.69), and 1.71 for stage 2 SDH (CI, 1.58 to 1.84). The cumulative risk for cardiovascular events also increased gradually across BP stages, ranging from 14.7% for normal BP to 24.3% for stage 2 SDH at age 68 years. Limitation: This was an observational study of Swedish men. Conclusion: Increasing BP levels in late adolescence are associated with gradually increasing risks for major cardiovascular events, beginning at a BP level of 120/80 mm Hg. Primary Funding Source: Västerbotten County Council, Swedish Society for Medical Research, and Heart Foundation of Northern Sweden.

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.

How Would You Resuscitate This Patient With Septic Shock?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 176, No 2

Sepsis is a potentially life-threatening systemic dysregulatory response to infection, and septic shock occurs when sepsis leads to systemic vasodilation and subsequent tissue hypoperfusion. The Surviving Sepsis Campaign published updated guidelines in 2021 on the management of sepsis and septic shock. Here, in the context of a patient with septic shock, 2 critical care specialists discuss and debate conditional guideline recommendations on using lactate to guide resuscitation, the use of balanced crystalloids versus normal saline, and the use of corticosteroids.

How Would You Manage This Patient With Chronic Insomnia?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 175, No 12

Insomnia, which is characterized by persistent sleep difficulties in association with daytime dysfunction, is a common concern in clinical practice. Chronic insomnia disorder is defined as symptoms that occur at least 3 times per week and persist for at least 3 months. The American Academy of Sleep Medicine (AASM) published recent guidelines on behavioral and psychological treatment as well as pharmacologic therapy for chronic insomnia disorder. Regarding behavioral and psychological approaches, the only intervention strongly recommended was multicomponent cognitive behavioral therapy for insomnia. Regarding pharmacologic treatment, the AASM, based on weak evidence, suggested a limited number of medications that might be useful and others that probably are not. Here, 2 clinicians with expertise in sleep disorders—one a clinical psychologist and the other a physician—debate the management of a patient with chronic insomnia who has been treated with medications. They discuss the role of behavioral and psychological interventions and pharmacologic therapy for chronic insomnia and how the primary care practitioner should approach such a patient.

Primary Occurrence of Cardiovascular Events After Adding Sodium–Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes

Background: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) is uncertain for those without preexisting cardiovascular disease. Objective: To test the hypothesis that MACE incidence was lower with the addition of GLP1RA or SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) for primary cardiovascular prevention. Design: Retrospective cohort study of U.S. veterans from 2001 to 2019. Setting: Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index. Patients: Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease. Measurements: Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates. Results: The cohort included 28 759 GLP1RA versus 28 628 DPP4i weighted pairs and 21 200 SGLT2i versus 21 170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1000 person-years. Sodium–glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [−1.12 to 3.32]) compared with DPP4i. Limitation: Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined. Conclusion: The addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use; SGLT2i addition was not associated with primary MACE prevention. Primary Funding Source: VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.