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Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study: Annals of Internal Medicine: Vol 166, No 1

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.

Readmission Rates After Passage of the Hospital Readmissions Reduction Program: A Pre–Post Analysis: Annals of Internal Medicine: Vol 166, No 5

Background: Whether hospitals with the highest risk-standardized readmission rates (RSRRs) subsequently experienced the greatest improvement after passage of the Medicare Hospital Readmissions Reduction Program (HRRP) is unknown. Objective: To evaluate whether passage of the HRRP was followed by acceleration in improvement in 30-day RSRRs after hospitalizations for acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia and whether the lowest-performing hospitals had faster acceleration in improvement after passage of the law than hospitals that were already performing well. Design: Pre–post analysis stratified by hospital performance groups. Setting: U.S. acute care hospitals. Patients: 15 170 008 Medicare patients discharged alive from 2000 to 2013. Intervention: Passage of the HRRP. Measurements: 30-day readmission rates after hospitalization for AMI, CHF, or pneumonia for hospitals in the highest-performance (0% penalty), average-performance (>0% and <0.50% penalty), low-performance (≥0.50% and <0.99% penalty), and lowest-performance (≥0.99% penalty) groups. Results: Of 2868 hospitals serving 1 109 530 Medicare discharges annually, 30.1% were highest performers, 44.0% were average performers, 16.8% were low performers, and 9.0% were lowest performers. After controlling for prelaw trends, an additional 67.6 (95% CI, 66.6 to 68.4), 74.8 (CI, 74.0 to 75.4), 85.4 (CI, 84.0 to 86.8), and 95.1 (CI, 92.6 to 97.5) readmissions per 10 000 discharges were found to have been averted per year in the highest-, average-, low-, and lowest-performance groups, respectively, after passage of the law. Limitation: Inability to distinguish between improvement caused by the magnitude of the penalty or by different levels of health improvement in different patient populations. Conclusion: After passage of the HRRP, 30-day RSRRs for myocardial infarction, heart failure, and pneumonia decreased more rapidly than before the law's passage. Improvement was most marked for hospitals with the lowest prelaw performance. Primary Funding Source: National Institutes of Health.

Candidatus Rickettsia tarasevichiae Infection in Eastern Central China: A Case Series: Annals of Internal Medicine: Vol 164, No 10

Background: Human infection with Candidatus Rickettsia tarasevichiae (CRT) was first reported in northeastern China in 2012. Objective: To describe the clinical spectrum and laboratory findings of patients infected with CRT in eastern central China. Design: Case series. Setting: A sentinel hospital for severe fever with thrombocytopenia syndrome (SFTS) in eastern central China in 2014. Participants: Hospitalized patients with SFTS-like illness. Measurements: Molecular and serologic tests were performed to diagnose CRT infection. Data about clinical manifestations and laboratory findings were retrieved from medical records. Results: 56 of 733 assessed patients had CRT based on polymerase chain reaction and sequencing. All patients presented with nonspecific manifestations, including fever (96%), malaise (88%), myalgia (57%), cough (25%), and dizziness (14%). Only 2 patients had rash. Further, 16% had eschar, 29% had lymphadenopathy, 100% had gastrointestinal symptoms, 34% had neurologic symptoms, 43% had hemorrhagic manifestations, and 23% had signs of plasma leakage. Thrombocytopenia was observed in 70%, leukopenia in 59%; lymphopenia in 45%; and elevated levels of lactate dehydrogenase in 82%, aspartate aminotransferase in 70%, alanine aminotransferase in 54%, and creatinine kinase in 46%. Co-infection with SFTS virus was documented in 66% patients, and 8 of the 56 patients died. Limitations: Patients with CRT were not treated for infection because they were retrospectively identified. This was not a population-based study, and the results cannot be generalized to all patients with CRT. Conclusion: Candidatus R tarasevichiae infection should be considered in the differential diagnosis of febrile patients with SFTS-like illness in endemic areas. Primary Funding Source: National Natural Science Foundation of China.

Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 165, No 3

Background: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. Objective: To investigate the incidence of vascular events in patients with CML treated with first- and second-generation TKIs. Design: Retrospective cohort study using nationwide population-based registries. Setting: Sweden. Patients: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. Results: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. Limitations: Patients may have been exposed to multiple TKIs. Data on second- and third-generation TKIs were limited. Conclusion: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs. Primary Funding Source: No external funding.

Relationship Among Body Fat Percentage, Body Mass Index, and All-Cause Mortality: A Cohort Study: Annals of Internal Medicine: Vol 164, No 8

Background: Prior mortality studies have concluded that elevated body mass index (BMI) may improve survival. These studies were limited because they did not measure adiposity directly. Objective: To examine associations of BMI and body fat percentage (separately and together) with mortality. Design: Observational study. Setting: Manitoba, Canada. Participants: Adults aged 40 years or older referred for bone mineral density (BMD) testing. Measurements: Participants had dual-energy x-ray absorptiometry (DXA), entered a clinical BMD registry, and were followed using linked administrative databases. Adjusted, sex-stratified Cox models were constructed. Body mass index and DXA-derived body fat percentage were divided into quintiles, with quintile 1 as the lowest, quintile 5 as the highest, and quintile 3 as the reference. Results: The final cohort included 49 476 women (mean age, 63.5 years; mean BMI, 27.0 kg/m2; mean body fat, 32.1%) and 4944 men (mean age, 65.5 years; mean BMI, 27.4 kg/m2; mean body fat, 29.5%). Death occurred in 4965 women over a median of 6.7 years and 984 men over a median of 4.5 years. In fully adjusted mortality models containing both BMI and body fat percentage, low BMI (hazard ratio [HR], 1.44 [95% CI, 1.30 to 1.59] for quintile 1 and 1.12 [CI, 1.02 to 1.23] for quintile 2) and high body fat percentage (HR, 1.19 [CI, 1.08 to 1.32] for quintile 5) were associated with higher mortality in women. In men, low BMI (HR, 1.45 [CI, 1.17 to 1.79] for quintile 1) and high body fat percentage (HR, 1.59 [CI, 1.28 to 1.96] for quintile 5) were associated with increased mortality. Limitations: All participants were referred for BMD testing, which may limit generalizability. Serial measures of BMD and weight were not used. Some measures, such as physical activity and smoking, were unavailable. Conclusion: Low BMI and high body fat percentage are independently associated with increased mortality. These findings may help explain the counterintuitive relationship between BMI and mortality. Primary Funding Source: None.

Mechanical Symptoms and Arthroscopic Partial Meniscectomy in Patients With Degenerative Meniscus Tear: A Secondary Analysis of a Randomized Trial: Annals of Internal Medicine: Vol 164, No 7

Background: Recent evidence shows that arthroscopic partial meniscectomy (APM) offers no benefit over conservative treatment of patients with a degenerative meniscus tear. However, patients who report mechanical symptoms (sensations of knee catching or locking) may benefit from APM. Objective: To assess whether APM improves mechanical symptoms better than sham surgery. Design: Randomized, patient- and outcome assessor–blinded, sham surgery–controlled, multicenter trial. (ClinicalTrials.gov: NCT00549172) Setting: 5 orthopedic clinics in Finland. Patients: Adults (aged 35 to 65 years) with a degenerative medial meniscus tear and no knee osteoarthritis. Intervention: APM or sham surgery. Measurements: Patients' self-report of mechanical symptoms before surgery and at 2, 6, and 12 months after surgery. Results: 70 patients were randomly assigned to APM, and 76 were assigned to sham surgery. Thirty-two patients (46%) in the APM group and 37 (49%) in the sham surgery group reported catching or locking before surgery; the corresponding numbers at any follow-up were 34 (49%) and 33 (43%), with a risk difference of 0.03 (95% CI, −0.06 to 0.12). In the subgroup of 69 patients with preoperative catching or locking, the risk difference was 0.07 (CI, −0.08 to 0.22). Limitation: Analyses were post hoc, and the results are only generalizable to knee catching and occasional locking because few patients reported other types of mechanical symptoms. Conclusion: Resection of a torn meniscus has no added benefit over sham surgery to relieve knee catching or occasional locking. These findings question whether mechanical symptoms are caused by a degenerative meniscus tear and prompt caution in using patients' self-report of these symptoms as an indication for APM. Primary Funding Source: Academy of Finland.

The Patient-Centered Medical Home and Associations With Health Care Quality and Utilization: A 5-Year Cohort Study: Annals of Internal Medicine: Vol 164, No 6

Background: Effects of the patient-centered medical home (PCMH) are unclear. Previous studies had relatively short follow-up and may not have distinguished effects of the PCMH (which involves electronic health records [EHRs] plus organizational changes) from those of EHRs alone. Objective: To determine effects of the PCMH on health care quality and utilization compared with paper records alone and EHRs alone, with extended follow-up. Design: Prospective cohort study (2008 to 2012), including 3 years after PCMH implementation. (ClinicalTrials.gov: NCT00793065) Setting: The Hudson Valley, a multipayer, multiprovider region in New York. Participants: 438 primary care physicians in 226 practices, with 136 480 patients across 5 health plans. Intervention: Level III PCMH, as defined by the National Committee for Quality Assurance. Measurements: Claims-based outcomes included 8 quality and 7 utilization measures. Generalized estimating equations were used to compare adjusted differences in rates of change across study groups. Results: Patterns of quality were fairly similar across groups. Utilization patterns were similar across groups from 2008 to 2011 but showed modest differences between the PCMH and control groups on most measures in 2012. For example, hospitalizations were relatively stable from 2008 to 2011 (approximately 3.9 to 5.2 per 100 patients per year) but decreased in the PCMH group in 2012 (incidence rate ratio, 0.79 [95% CI, 0.69 to 0.90] compared with paper records). Emergency department visits were highest for the PCMH group (16.7 per 100 patients at baseline and 15.4 per 100 patients at the end of the study period) and lowest for the paper group (14.3 per 100 patients at baseline and 12.2 per 100 patients at the end of the study period), but the rate of change did not differ across groups. Limitation: Possible unmeasured confounding. Conclusion: The PCMH was associated with modest changes in most utilization measures and provided similar quality compared with EHRs and paper records. Primary Funding Source: The Commonwealth Fund and the New York State Department of Health.

Twenty-Three–Year Benefits of Sigmoidoscopy Screening for Colorectal Cancer: A Randomized Trial: Annals of Internal Medicine: Vol 0, No 0

Background: Meta-analyses of randomized trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and death for 15 years. Objective: To report the benefits of sigmoidoscopy after 23 years. Design: Randomized controlled trial. (NORCCAP [Norwegian Colorectal Cancer Prevention], ClinicalTrials.gov: NCT00119912) Setting: Population of Oslo and Telemark County, Norway. Participants: Persons aged 50 to 64 years without CRC at randomization. Intervention: Screening with once-only sigmoidoscopy, with or without 1 fecal immunochemical test, or no screening. Measurements: Colorectal cancer incidence and death. Results: A total of 100 210 persons were randomly assigned, and 98 654 were included in intention-to-screen analyses: 20 552 in the screening group and 78 102 in the no-screening group. Participation with screening was 61.4% in men and 64.7% in women. In men, the 23-year cumulative risk for CRC was 4.3% in the screening group and 6.0% in the no-screening group, corresponding to a risk difference of −1.7 percentage points (95% CI, −2.2 to −1.2 percentage points). In women, the corresponding risks were 4.2% and 4.7%, yielding a risk difference of −0.5 percentage points (CI, −1.0 to −0.01 percentage points). In men, the 23-year cumulative risk for CRC death was 1.4% in the screening group and 2.2% in the no-screening group, corresponding to a risk difference of −0.8 percentage points (CI, −1.1 to −0.5 percentage points). In women, the corresponding risks were 1.3% and 1.4%, yielding a risk difference of −0.1 percentage points (CI, −0.3 to 0.1 percentage points). The effect was strongest for rectosigmoid cancer. The addition of fecal blood testing to sigmoidoscopy did not change screening benefits. Limitation: Follow-up through national registries. Conclusion: Offering sigmoidoscopy screening in Norway reduced CRC incidence more in men than in women and reduced CRC death only in men. Primary Funding Source: Norwegian government and Norwegian Cancer Society.

Prevention of Recurrent Nephrolithiasis in Adults and Children: A Systematic Review: Annals of Internal Medicine: Vol 179, No 5

Background: Recurrent kidney stones are unpleasant and may lead to kidney damage, sepsis, or invasive procedures. Purpose: To assess benefits and harms of diet, pharmacologic therapy, and surveillance imaging to prevent recurrent nephrolithiasis. Data Sources: PubMed, Cochrane Library, and trial registries through December 2025. Study Selection: Randomized controlled trials (RCTs) or nonrandomized studies of interventions (NRSIs) in nonpregnant adults or children. Data Extraction: One reviewer extracted data, and a second reviewer checked for accuracy. Dual independent assessments of risk of bias and strength of evidence (SOE) were done. Data Synthesis: Among 31 studies (26 RCTs and 5 NRSIs), none evaluated imaging strategies. All but 3 included adults only. For adults with calcium oxalate or phosphate stones, increased water intake; a diet with normal to high calcium, low protein, and low sodium; thiazides; alkali treatment; and allopurinol may reduce stone recurrence (low SOE). There may be no difference between selective and empirical pharmacotherapy (low SOE). Acetohydroxamic acid may reduce stone growth in adults with infection-related stones (low SOE) but had insufficient evidence on prevention of recurrent stones and probably increased adverse events (moderate SOE). There may be increased minor adverse events with lemon juice but no increased harm due to serious adverse events with thiazides and allopurinol (low SOE). Limitation: Studies not published in English or with fewer than 30 participants per group were excluded. Conclusion: Increased fluid intake; a diet with normal to high calcium, low protein, and low sodium; thiazides; alkali therapy; and allopurinol may prevent stone recurrence in adults with calcium oxalate or calcium phosphate stones. Evidence is limited on other interventions, including imaging strategies, in children and on harms and other outcomes. Primary Funding Source: Patient-Centered Outcomes Research Institute and Agency for Healthcare Research and Quality (contract no. 75Q80120D00007/75Q80124F32010). (PROSPERO: CRD42024617257)

Exposure to Computed Tomography Before Pregnancy and Risk for Pregnancy Loss and Congenital Anomalies: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 178, No 11

Background: Animal studies show ovarian follicle damage and mutagenesis after ionizing radiation exposure. Computed tomography (CT) imaging is commonly done outside pregnancy, but risks to future pregnancy are unknown. Objective: To evaluate the risk for spontaneous pregnancy loss and congenital anomalies in offspring of women exposed to CT ionizing radiation before conception. Design: Population-based observational study. Setting: Ontario, Canada. Participants: 5 142 339 recognized pregnancies and 3 451 968 live births identified between 1992 and 2023. Measurements: The exposure was the cumulative number of CT scans up to 4 weeks before conception. Outcomes were spontaneous pregnancy loss (miscarriage, ectopic pregnancy, or stillbirth) among recognized pregnancies and congenital anomalies diagnosed within the first year of life among live births. Results: Mean maternal age was 29 years. Diabetes, hypertension, obesity, and smoking were more common in those exposed to CT imaging. Among recognized pregnancies, rates of spontaneous pregnancy loss were 101, 117, 130, and 142 per 1000 pregnancies with 0, 1, 2, and 3 or more preconception CT scans, respectively, and adjusted hazard ratios (aHRs) were 1.08 (95% CI, 1.07 to 1.08) for 1 CT scan, 1.14 (CI, 1.12 to 1.16) for 2 CT scans, and 1.19 (CI, 1.16 to 1.21) for 3 or more CT scans. Among live births, rates of congenital anomalies were 62, 84, 96, and 105 per 1000 births in those with 0, 1, 2, and 3 or more CT scans, and aHRs were 1.06 (CI, 1.05 to 1.08) for 1 CT scan, 1.11 (CI, 1.09 to 1.14) for 2 CT scans, and 1.15 (CI, 1.11 to 1.18) for 3 or more CT scans. The risk observed with head CT was not consistently lower than with CT of the abdomen, pelvis, or lower spine. Limitation: Incomplete ascertainment of CT exposure and underlying indication may have contributed to residual confounding. Conclusion: Exposure to preconception CT imaging may be associated with higher risks for spontaneous pregnancy loss and congenital anomalies, but causal mechanisms remain to be elucidated. Alternative imaging methods should be considered when appropriate. Primary Funding Source: Canadian Institutes of Health Research.

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