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PurposePatients with estrogen receptor positive (ER+) breast cancer are often non-adherent to endocrine therapies, despite clear survival benefits. We utilized a nationally representative cancer cohort to examine the role of specific mental illnesses on endocrine therapy adherence.MethodsUsing the SEER-Medicare database, we included 21,894 women aged 68+ at their first surgically treated stage I-IV ER+ breast cancer during 2007–2013. All had continuous fee-for-service Medicare Parts A and B for 36+ months before, 18+ months after diagnosis, and continuous Part D for 4+ months before, 18+ after diagnosis. Mental illness was defined as occurring in the 36 months prior to cancer onset. We analyzed endocrine therapy adherence, initiation, and discontinuation using longitudinal linear and Cox regression models.ResultsUnipolar depression (11.0%), anxiety (9.5%), non-schizophrenia psychosis (4.6%), and dementias (4.6%) were the most prevalent diagnoses. Endocrine therapies were initiated by 80.0% of women. Among those with at least one year of use, 28.0% were non-adherent (< 0.80 adherence, mean = 0.84) and 25.7% discontinued. Patients with dementia or bipolar depression/psychotic/schizophrenia disorders had lower adjusted initiation probabilities by year one of follow-up, versus those without these diagnoses [0.74 95% CI (0.73–0.74) and 0.73 (0.72–0.73), respectively, reference 0.76 (0.76–0.77)]. Patients with substance use or anxiety disorders less frequently continued endocrine therapy for at least one year, after adjustment, [0.85 95% CI (0.85–0.86) and 0.88 (0.87–0.88), respectively, reference 0.90 (0.89–0.90)]. Patients with substance use disorders had 2.3% lower adherence rates (p < 0.001).ConclusionsNearly one-quarter of female Medicare beneficiaries have diagnosed mental illness preceding invasive breast cancer. Those with certain mental illnesses have modestly reduced rates of initiation, adherence, and discontinuation and this may help define patients at higher risk of treatment abandonment. Overall, endocrine therapy adherence remains suboptimal, unnecessarily worsening recurrence and mortality risk.

This study evaluates biopsychosocial factors as mediators of the effect of chiropractic care on low back pain (LBP) intensity and interference for active-duty military members. Data from a multi-site, pragmatic clinical trial comparing six weeks of chiropractic care plus usual medical care to usual medical care alone for 750 US active-duty military members with LBP were analyzed using natural-effect, multiple-mediator modeling. Mediation of the adjusted mean effect difference on 12-week outcomes of PROMIS-29 pain interference and intensity by 6-week mediators of other PROMIS-29 physical, mental, and social health subdomains was evaluated. The effect difference on pain interference occurring through PROMIS-29 biopsychosocial factors (natural indirect effect = -1.59, 95% CI = -2.28 to -0.88) was 56% (95% CI = 35 to 96) of the total effect (-2.82, 95% CI = -3.98 to -1.53). The difference in effect on pain intensity occurring through biopsychosocial factors was smaller (natural indirect effect = -0.32, 95% CI = -0.50 to -0.18), equaling 26% (95% CI = 15 to 42) of the total effect (-1.23, 95% CI = -1.52 to -0.88). When considered individually, all physical, mental, and social health factors appeared to mediate the effect difference on pain interference and pain intensity with mental health factors having smaller effect estimates. In contrast with effects on pain interference, much of the effect of adding chiropractic care to usual medical care for US military members on pain intensity did not appear to occur through the PROMIS-29 biopsychosocial factors. Physical and social factors appear to be important intermediate measures for patients receiving chiropractic care for low back pain in military settings. Further study is needed to determine if the effect of chiropractic care on pain intensity for active-duty military occurs through other unmeasured factors, such as patient beliefs, or if the effect occurs directly.

The risk of cardiovascular outcomes following SARS-CoV-2 infection has been reported in adults, but evidence in children and adolescents is limited. This paper assessed the risk of a multitude of cardiac signs, symptoms, and conditions 28-179 days after infection, with outcomes stratified by the presence of congenital heart defects (CHDs), using electronic health records (EHR) data from 19 children’s hospitals and health institutions from the United States within the RECOVER consortium between March 2020 and September 2023. The cohort included 297,920 SARS-CoV-2-positive individuals and 915,402 SARS-CoV-2-negative controls. Every individual had at least a six-month follow-up after cohort entry. Here we show that children and adolescents with prior SARS-CoV-2 infection are at a statistically significant increased risk of various cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations, compared to uninfected controls. These findings were consistent among patients with and without CHDs. Awareness of the heightened risk of cardiovascular disorders after SARS-CoV-2 infection can lead to timely referrals, diagnostic evaluations, and management to mitigate long-term cardiovascular complications in children and adolescents. Post-acute sequelae of SARS-CoV-2 infection affecting the cardiovascular system have been reported, but evidence in young people is limited. Here, the authors quantify the incidence of a range of outcomes in children and adolescents using electronic health records from the United States.

Abstract Introduction The purpose of this study was to explore the association of smoking status and clinically relevant duration of smoking cessation with long-term survival after lung cancer (LC) or colorectal cancer (CRC) diagnosis. We compared survival of patients with LC and CRC who were never-smokers, long-term, medium-term, and short-term quitters, and current smokers around diagnosis. Methods We studied 5575 patients in Cancer Care Outcomes Research and Surveillance (CanCORS), a national, prospective observational cohort study, who provided smoking status information approximately 5 months after LC or CRC diagnosis. Smoking status was categorized as: never-smoker, quit >5 years prior to diagnosis, quit between 1–5 years prior to diagnosis, quit less than 1 year before diagnosis, and current smoker. We examined the relationship between smoking status around diagnosis with mortality using Cox regression models. Results Among participants with LC, never-smokers had lower mortality risk compared with current smokers (HR 0.71, 95% CI 0.57 to 0.89). Among participants with CRC, never-smokers had a lower mortality risk as compared to current smokers (HR 0.79, 95% CI 0.64 to 0.99). Conclusions Among both LC and CRC patients, current smokers at diagnosis have higher mortality than never-smokers. This effect should be further studied in the context of tumor biology. However, smoking cessation around the time of diagnosis did not affect survival in this sample. Implications The results from our analysis of patients in the CanCORS consortium, a large, geographically diverse cohort, show that both LC and CRC patients who were actively smoking at diagnosis have worse survival as compared to never-smokers. While current smoking is detrimental to survival, cessation upon diagnosis may not mitigate this risk.

Background Clostridium difficile is the most common cause of nosocomial infectious diarrhea in the United States. However, recent reports have documented that C. difficile infections (CDIs) are occurring among patients without traditional risk factors. The purpose of this study was to examine the epidemiology of CA-CDI, by estimating the incidence of CA-CDI and HA-CDI, identifying patient-related risk factors for CA-CDI, and describing adverse health outcomes of CA-CDI. Methods We conducted a population-based, retrospective, nested, case-control study within the University of Iowa Wellmark Data Repository from January 2004 to December 2007. We identified persons with CDI, determined whether infection was community-associated (CA) or hospital-acquired (HA), and calculated incidence rates. We collected demographic, clinical, and pharmacologic information for CA-CDI cases and controls (i.e., persons without CDI). We used conditional logistic regression to estimate the odds ratios (ORs) for potential risk factors for CA-CDI. Results The incidence rates for CA-CDI and HA-CDI were 11.16 and 12.1 cases per 100,000 person-years, respectively. CA-CDI cases were more likely than controls to receive antimicrobials (adjusted OR, 6.09 [95% CI 4.59-8.08]) and gastric acid suppressants (adjusted OR, 2.30 [95% CI 1.56-3.39]) in the 180 days before diagnosis. Controlling for other covariates, increased risk for CA-CDI was associated with use of beta-lactam/beta-lactamase inhibitors, cephalosporins, clindamycin, fluoroquinolones, macrolides, and penicillins. However, 27% of CA-CDI cases did not receive antimicrobials in the 180 days before their diagnoses, and 17% did not have any traditional risk factors for CDI. Conclusions Our study documented that the epidemiology of CDI is changing, with CA-CDI occurring in populations not traditionally considered \"high-risk\" for the disease. Clinicians should consider this diagnosis and obtain appropriate diagnostic testing for outpatients with persistent or severe diarrhea who have even remote antimicrobial exposure.

IntroductionLow back pain (LBP) is a key source of medical costs and disability, impacting over 31 million Americans at any given time and resulting in US$100–US$200 billion per year in total healthcare costs. LBP is one of the leading causes of ambulatory care visits to US physicians; problematically, these visits often result in treatments such as opioids, surgery or advanced imaging that can lead to more harm than benefit. The American College of Physicians (ACP) Guideline for Low Back Pain recommends patients receive non-pharmacological interventions as a first-line treatment. Roadmaps exist for multidisciplinary collaborative care that include well-trained primary contact clinicians with specific expertise in the treatment of musculoskeletal conditions, such as physical therapists and doctors of chiropractic, as first-line providers for LBP. These clinicians, sometimes referred to as primary spine practitioners (PSPs) routinely employ many of the non-pharmacological approaches recommended by the ACP guideline, including spinal manipulation and exercise. Important foundational work has demonstrated that such care is feasible and safe, and results in improved physical function, less pain, fewer opioid prescriptions and reduced utilisation of healthcare services. However, this treatment approach for LBP has yet to be widely implemented or tested in a multisite clinical trial in real-world practice.Methods and analysisThe Implementation of the American College of Physicians Guideline for Low Back Pain trial is a health system-embedded pragmatic cluster-randomised trial that will examine the effect of offering initial contact with a PSP compared with usual primary care for LBP. Twenty-six primary care clinics within three healthcare systems were randomised 1:1 to PSP intervention or usual primary care. Primary outcomes are pain interference and physical function using the Patient-Reported Outcomes Measurement Information System Short Forms collected via patient self-report among a planned sample of 1800 participants at baseline, 1, 3 (primary end point), 6 and 12 months. A subset of participants enrolled early in the trial will also receive a 24-month assessment. An economic analysis and analysis of healthcare utilisation will be conducted as well as an evaluation of the patient, provider and policy-level barriers and facilitators to implementing the PSP model using a mixed-methods process evaluation approach.Ethics and disseminationThe study received ethics approval from Advarra, Duke University, Dartmouth Health and the University of Iowa Institutional Review Boards. Study data will be made available on completion, in compliance with National Institutes of Health data sharing policies.Trial registration numberNCT05626049.

Purpose Evidence of the impact of the COVID‐19 pandemic on cancer prevention and control is growing, but little is known about patient‐level factors associated with delayed care. We analyzed data from a survey focused on Iowan cancer patients' COVID‐19 experiences in the early part of the pandemic. Methods Participants were recruited from the University of Iowa Holden Comprehensive Cancer Center's Patients Enhancing Research Collaborations at Holden (PERCH) program. We surveyed respondents on demographic characteristics, COVID‐19 experiences and reactions, and delays in any cancer‐related health care appointment, or cancer‐related treatment appointments. Two‐sided significance tests assessed differences in COVID‐19 experiences and reactions between those who experienced delays and those who did not. Results There were 780 respondents (26% response), with breast, prostate, kidney, skin, and colorectal cancers representing the majority of respondents. Delays in cancer care were reported by 29% of respondents. In multivariable‐adjusted models, rural residents (OR 1.47; 95% CI 1.03, 2.11) and those experiencing feelings of isolation (OR 2.18; 95% CI 1.37, 3.47) were more likely to report any delay, where experiencing financial difficulties predicted delays in treatment appointments (OR 5.72; 95% CI 1.96, 16.67). Health insurance coverage and concern about the pandemic were not statistically significantly associated with delays. Conclusion These findings may inform cancer care delivery during periods of instability when treatment may be disrupted by informing clinicians about concerns that patients have during the treatment process. Future research should assess whether delays in cancer care impact long‐term cancer outcomes and whether delays exacerbate existing disparities in cancer outcomes. This manuscript assesses impacts of the COVID‐19 pandemic on cancer‐related medical care among cancer patients receiving care at an academic medical center. We report delays for any cancer care and by treatment type mid‐pandemic and differences between those who experienced delays in care and those who did not in perceptions of social distancing measures, use of social distancing measures, and pandemic‐related concern.

Background Acute Kidney Injury (AKI) can adversely affect multiple organ systems, including the heart, brain, and immune system. Stage 1 AKI (AKI-1), although mild in clinical presentation, constitutes a substantial subset of AKI patients with heterogeneous outcomes, warranting further investigation into its subphenotypes. Methods We performed clustering analysis on seven-day serum creatinine (SCr) trajectories preceding AKI-1 onset in 53,565 AKI-1 patients (aged 18–89 years; 55.57% male) across eight academic hospitals. Each AKI-1 patient was matched to a non-AKI counterpart to evaluate how different AKI-1 subphenotypes influence clinical indicators and outcomes. Results Three distinct AKI-1 subphenotypes are identified. Patients in Subphenotype C ( n  = 5,378; 10.0%) exhibit a higher proportion of abnormal values across clinical indicators compared to those in Subphenotypes A ( n  = 27,049; 50.5%) and B ( n  = 21,138; 39.5%). Subphenotype C is associated with significantly higher odds ratios (ORs) for in-hospital, 30-day, and one-year all-cause mortality relative to Subphenotypes A and B. Conversely, Subphenotype B exhibits a higher susceptibility to developing chronic kidney disease (CKD) within one year after discharge following AKI-1, compared to both Subphenotypes A and C, after adjustment for baseline SCr levels. All AKI-1 subphenotypes are associated with significantly elevated risks of all-cause mortality and the need for dialysis or renal replacement therapy (RRT) compared to their respective non-AKI counterparts. Conclusions This study reveals substantial heterogeneity in clinical indicators and outcomes within AKI-1. Future research focusing on these subphenotypes may pave the way for more personalized and targeted interventions for patients with AKI-1. Plain language summary Stage 1 acute kidney injury (AKI-1) is the mildest form of sudden kidney damage, usually identified by a small rise in a blood waste marker called creatinine or a slight drop in urine output. Although AKI-1 may seem mild at first, it can still lead to serious consequences. This study investigated whether there are subtypes of AKI-1 that carry different health risks. Using hospital data from 53,565 patients, we grouped patients based on how their serum creatinine (kidney function biomarker) change over time, and found three distinct subtypes of AKI-1, each linked to different health outcomes. One subtype had a significantly higher risk of death, while another subtype was more likely to develop chronic kidney disease (CKD) after hospital discharge. These findings could help doctors provide more personalized care to patients with AKI-1. Li et al. identify three subphenotypes of stage-1 Acute Kidney Injury based on serum creatinine trajectories prior to onset. These subphenotypes show distinct clinical profiles and outcomes, suggesting opportunities for more personalized stage-1 Acute Kidney Injury management.

BACKGROUND:Guidelines suggest statin use after acute myocardial infarction (AMI) should be close to universal in patients without safety concerns yet rates are much lower than recommended, decline with patient complexity, and display substantial geographic variation. Trial exclusions have resulted in little evidence to guide statin prescribing for complex patients. OBJECTIVE:To assess the benefits and risks associated with higher rates of statin use after AMI by baseline patient complexity. RESEARCH DESIGN:Sample includes Medicare fee-for-service patients with AMIs in 2008–2009. Instrumental variable estimators using variation in local area prescribing patterns by statin intensity as instruments were used to assess the association of higher statin prescribing rates by statin intensity on 1-year survival, adverse events, and cost by patient complexity. RESULTS:Providers seem to have individualized statin use across patients based on potential risks. Higher statin rates for noncomplex AMI patients were associated with increased survival rates with little added adverse event risk. Higher statin rates for complex AMI patients were associated with tradeoffs between higher survival rates and higher rates of adverse events. CONCLUSIONS:Higher rates of statin use for noncomplex AMI patients are associated with outcome rate changes similar to existing evidence. For the complex patients in our study, who were least represented in existing trials, higher statin-use rates were associated with survival gains and higher adverse event risks not previously documented. Policy interventions promoting higher statin-use rates for complex patients may need to be reevaluated taking careful consideration of these tradeoffs.

Precis Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients. Background Despite national guidelines, debate exists among clinicians regarding the optimal approach to treatment for patients diagnosed with ductal carcinoma in situ (DCIS). While regional variation in practice patterns has been well documented, population‐based information on rural–urban treatment differences is lacking. Methods Data from the SEER Patterns of Care studies were used to identify women diagnosed with histologically confirmed DCIS who underwent cancer‐directed surgery in the years 1991, 1995, 2000, 2005, 2010, and 2015. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using weighted multivariable logistic regression to evaluate cancer‐directed surgery and use of post‐operative radiation therapy (PORT). Results Of the 3337 patients who met inclusion criteria, 27% underwent mastectomy, 26% underwent breast‐conserving surgery (BCS) without PORT, and 47% underwent BCS with PORT. After adjustment for other covariates, there was no difference in the likelihood of receiving mastectomy between rural and urban patients (aOR = 0.65; 95% CI 0.37–1.14). However, rural residents were more likely than urban residents to have mastectomy during 1991/1995 (aOR = 1.78; 95% CI 1.09–2.91; pinteraction = 0.022). Across all diagnosis years, patients residing in rural areas were less likely to receive PORT following BCS compared to urban patients (aOR = 0.35; 95% CI 0.18–0.67). Conclusions Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients. Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients.