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Chronic hyponatremia may contribute to decreased bone density. We studied 341,003 men and women who underwent DXA testing and observed that individuals with chronic hyponatremia (sodium

ContextPatient reported outcomes (PROs) are one means of systematically gathering meaningful subjective information for patient care, population health, and patient centered outcomes research. However, optimal data management for effective PRO applications is unclear.Case descriptionDelivery systems associated with the Health Care Systems Research Network (HCSRN) have implemented PRO data collection as part of the Medicare annual Health Risk Assessment (HRA). A questionnaire assessed data content, collection, storage, and extractability in HCSRN delivery systems.FindingsResponses were received from 15 (83.3 percent) of 18 sites. The proportion of Medicare beneficiaries completing an HRA ranged from less than 10 to 42 percent. Most sites collected core HRA elements and 10 collected information on additional domains such as social support. Measures for core domains varied across sites. Data were collected at and prior to visits. Modes included paper, clinician entry, patient portals, and interactive voice response. Data were stored in the electronic health record (EHR) in scanned documents, free text, and discrete fields, and in summary databases.Major themesPRO implementation requires effectively collecting, storing, extracting, and applying patient-reported data. Standardizing PRO measures and storing data in extractable formats can facilitate multi-site uses for PRO data, while access to individual PROs in the EHR may be sufficient for use at the point of care.ConclusionCollecting comparable PRO data elements, storing data in extractable fields, and collecting data from a higher proportion of eligible respondents represents an optimal approach to support multi-site applications of PRO information.

Permanent magnets have long been used in both traditional laboratory exercises and in inquiry-based learning activities. These pedagogical applications are typically timed to correspond to the early coverage of magnetism in the second-semester sequence of introductory physics. At the initial level the concepts relate to the magnetic field of the Earth, the magnetic forces on a magnetic dipole, the various classes of magnetic materials, the nature of the magnetic field in the vicinity of a permanent magnet, and perhaps the use of magnetic fields to produce electric currents. Although there are examples of quantitative experiments in magnetism and electromagnetism using permanent magnets, very rarely are these laboratories made part of the introductory laboratory experience.

The management of chronic conditions is characterized by frequent re-assessment of therapy decisions in response to the patient’s changing condition over the course of the illness. Evidence most suitable to inform care thus often concerns the contrast of adaptive treatment strategies that repeatedly personalize treatment decisions over time using the latest accumulated data available from the patient’s previous clinic visits such as laboratory exams (e.g., hemoglobin A1c measurements in diabetes care). The frequency at which such information is monitored implicitly defines the causal estimand that is typically evaluated in an observational or randomized study of such adaptive treatment strategies. Analytic control of monitoring with standard estimation approaches for time-varying interventions can therefore not only improve study generalizibility but also inform the optimal timing of clinical surveillance. Valid inference with these estimators requires the upholding of a positivity assumption that can hinder their applicability. To potentially weaken this requirement for monitoring control, we introduce identifiability results that will facilitate the derivation of alternate estimators of effects defined by general joint treatment and monitoring interventions in the context of time-to-event outcomes. These results are developed based on the nonparametric structural equation modeling framework using a no direct effect assumption originally introduced in a prior paper that inspired this work. The relevance and scope of the results presented here are illustrated with examples in diabetes comparative effectiveness research.

Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001) to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white) in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1) time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2) primary adherence (time from first prescription to prescription fill); (3) time until discontinuation of oral antidiabetic medication from first prescription; and (4) long-term adherence (amount dispensed versus amount prescribed) over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7) and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

Abstract Background The optimal retrieval of a literature search in biomedicine depends on the appropriate use of Medical Subject Headings (MeSH), descriptors and keywords among authors and indexers. We hypothesized that authors, investigators and indexers in four biomedical databases are not consistent in their use of terminology in Complementary and Alternative Medicine (CAM). Methods Based on a research question addressing the validity of spinal palpation for the diagnosis of neuromuscular dysfunction, we developed four search concepts with their respective controlled vocabulary and key terms. We calculated the frequency of MeSH, descriptors, and keywords used by authors in titles and abstracts in comparison to standard practices in semantic and analytic indexing in MEDLINE, MANTIS, CINAHL, and Web of Science. Results Multiple searches resulted in the final selection of 38 relevant studies that were indexed at least in one of the four selected databases. Of the four search concepts, validity showed the greatest inconsistency in terminology among authors, indexers and investigators. The use of spinal terms showed the greatest consistency. Of the 22 neuromuscular dysfunction terms provided by the investigators, 11 were not contained in the controlled vocabulary and six were never used by authors or indexers. Most authors did not seem familiar with the controlled vocabulary for validity in the area of neuromuscular dysfunction. Recently, standard glossaries have been developed to assist in the research development of manual medicine. Conclusions Searching biomedical databases for CAM is challenging due to inconsistent use of controlled vocabulary and indexing procedures in different databases. A standard terminology should be used by investigators in conducting their search strategies and authors when writing titles, abstracts and submitting keywords for publications.

Abstract Background Many health care professionals use spinal palpatory exams as a primary and well-accepted part of the evaluation of spinal pathology. However, few studies have explored the validity of spinal palpatory exams. To evaluate the status of the current scientific evidence, we conducted a systematic review to assess the content validity of spinal palpatory tests used to identify spinal neuro-musculoskeletal dysfunction. Methods Review of eleven databases and a hand search of peer-reviewed literature, published between 1965–2002, was undertaken. Two blinded reviewers abstracted pertinent data from the retrieved papers, using a specially developed quality-scoring instrument. Five papers met the inclusion/exclusion criteria. Results Three of the five papers included in the review explored the content validity of motion tests. Two of these papers focused on identifying the level of fixation (decreased mobility) and one focused on range of motion. All three studies used a mechanical model as a reference standard. Two of the five papers included in the review explored the validity of pain assessment using the visual analogue scale or the subjects' own report as reference standards. Overall the sensitivity of studies looking at range of motion tests and pain varied greatly. Poor sensitivity was reported for range of motion studies regardless of the examiner's experience. A slightly better sensitivity (82%) was reported in one study that examined cervical pain. Conclusions The lack of acceptable reference standards may have contributed to the weak sensitivity findings. Given the importance of spinal palpatory tests as part of the spinal evaluation and treatment plan, effort is required by all involved disciplines to create well-designed and implemented studies in this area.

Abstract Background Recent studies suggest that patients at greatest risk for diabetes complications are least likely to self-monitor blood glucose. However, these studies rely on self-reports of monitoring, an unreliable measure of actual behavior. The purpose of the current study was to examine the relationship between patient characteristics and self-monitoring in a large health maintenance organization (HMO) using test strips as objective measures of self-monitoring practice. Methods This cross-sectional study included 4,565 continuously enrolled adult managed care patients in eastern Massachusetts with diabetes. Any self-monitoring was defined as filling at least one prescription for self-monitoring test strips during the study period (10/1/92–9/30/93). Regular SMBG among test strip users was defined as testing an average of once per day for those using insulin and every other day for those using oral sulfonylureas only. Measures of health status, demographic data, and neighborhood socioeconomic status were obtained from automated medical records and 1990 census tract data. Results In multivariate analyses, lower neighborhood socioeconomic status, older age, fewer HbA1c tests, and fewer physician visits were associated with lower rates of self-monitoring. Obesity and fewer comorbidities were also associated with lower rates of self-monitoring among insulin-managed patients, while black race and high glycemic level (HbA1c>10) were associated with less frequent monitoring. For patients taking oral sulfonylureas, higher dose of diabetes medications was associated with initiation of self-monitoring and HbA1c lab testing was associated with more frequent testing. Conclusions Managed care organizations may face the greatest challenges in changing the self-monitoring behavior of patients at greatest risk for poor health outcomes (i.e., the elderly, minorities, and people living in low socioeconomic status neighborhoods).

Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip BMD T-score ≤ -2.5, measured from the CT scan using VirtuOst). We defined "treated" as at least six months of any osteoporosis medication by prescription fill data during follow-up; "not-treated" was no prescription fill. Sex-specific odds ratios of hip fracture for treated vs not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, BMD-treatment interaction, BMD, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2,211 patients) and 24.0% of the men (175/728 patients) were treated primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated vs not-treated was 0.26 (95% confidence interval: 0.21-0.33) for women and 0.21 (0.13-0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47-1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Context: Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association., Objective: To compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT., Design: Retrospective matched-cohort study (2005-2020)., Setting: An integrated healthcare delivery system in Southern California., Patients: Women aged 18-44 years were included. Patients with biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT)., Main Outcome Measures: Achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care)., Results: The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI: 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with co-existing PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (p=0.023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n=22), during (n=5), or after pregnancy/never (n=24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium <11.5 mg/dL [2.9 mmol/L]., Conclusions: We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L])., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Greater decline in bone health among people with HIV (PWH) has been documented but fracture risk and the impact of specific antiretroviral therapy (ART) regimens remain unclear., Setting: Retrospective analyses of electronic health record data from 3 US integrated health care systems., Methods: Fracture incidence was compared between PWH aged 40 years or older without prior fracture and demographically matched people without HIV (PWoH), stratified by age, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to estimate fracture risk associated with HIV infection. The association of tenofovir disoproxil fumarate (TDF) use and fracture risk was evaluated in a subset of PWH initiating ART., Results: Incidence of fracture was higher in PWH [13.6/1000 person-years, 95% confidence interval (CI): 13.0 to 14.3, n = 24,308] compared with PWoH (9.5, 95% CI: 9.4 to 9.7, n = 247,313). Compared with PWoH, the adjusted hazard ratio (aHR) for fracture among PWH was 1.24 (95% CI: 1.18 to 1.31). The association between HIV infection and fracture risk increased with age, with the lowest aHR (1.17, 95% CI: 1.10 to 1.25) among those aged 40-49 years and the highest aHR (1.89, 95% CI: 1.30 to 2.76) among those aged 70 years or older. Among PWH initiating ART (n = 6504), TDF was not associated with significant increase in fracture risk compared with non-TDF regimens (aHR: 1.18, 95% CI: 0.89 to 1.58)., Conclusions: Among people aged 40 years or older, HIV infection is associated with increased risk of fractures. Bone health screening from the age of 40 years may be beneficial for PWH. Large cohort studies with longer follow-up are needed to evaluate TDF effect and the potential benefit of early screening., Competing Interests: M.J.S., W.J.T., and M.A.H. received research funding for this study from Gilead Sciences, Inc. R.C.H. received research funding from Gilead Sciences, Inc. for an unrelated study. H.Z. received research funding from Merck for an unrelated study. W.J.T. received research funding from Pfizer, ViiV, Merck, Janssen, Moderna, and GlaxoSmithKline for unrelated studies. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 μg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas.

Combining genome assembly with population and functional genomics can provide valuable insights to development and evolution, as well as tools for species management. Here, we present a chromosome-level genome assembly of the common brushtail possum (Trichosurus vulpecula), a model marsupial threatened in parts of their native range in Australia, but also a major introduced pest in New Zealand. Functional genomics reveals post-natal activation of chemosensory and metabolic genes, reflecting unique adaptations to altricial birth and delayed weaning, a hallmark of marsupial development. Nuclear and mitochondrial analyses trace New Zealand possums to distinct Australian subspecies, which have subsequently hybridised. This admixture allowed phasing of parental alleles genome-wide, ultimately revealing at least four genes with imprinted, parent-specific expression not yet detected in other species (MLH1, EPM2AIP1, UBP1 and GPX7). We find that reprogramming of possum germline imprints, and the wider epigenome, is similar to eutherian mammals except onset occurs after birth. Together, this work is useful for genetic-based control and conservation of possums, and contributes to understanding of the evolution of novel mammalian epigenetic traits., (© 2023. Springer Nature Limited.)

Importance: Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT)., Objective: To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes., Design: Matched control study., Setting: A vertically integrated health care system serving 4.6 million patients in Southern California., Participants: 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016., Exposures: Biochemically confirmed PHPT with varying serum calcium levels., Main Outcomes: Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively., Results: Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity score–matched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year)., Conclusions and Relevance: Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Context: While osteoporosis is a risk factor for adverse outcomes in spinal fusion patients, diagnosing osteoporosis reliably in this population has been challenging due to degenerative changes and spinal deformities. Addressing that challenge, biomechanical computed tomography analysis (BCT) is a CT-based diagnostic test for osteoporosis that measures both bone mineral density and bone strength (using finite element analysis) at the spine; CT scans taken for spinal evaluation or previous care can be repurposed for the analysis., Purpose: Assess the effectiveness of BCT for preoperatively identifying spinal fusion patients with osteoporosis who are at high risk of reoperation or vertebral fracture., Study Design: Observational cohort study in a multi-center integrated managed care system using existing data from patient medical records and imaging archives., Patient Sample: We studied a randomly sampled subset of all adult patients who had any type of primary thoracic (T4 or below) or lumbar fusion between 2005 and 2018. For inclusion, patients with accessible study data needed a preop CT scan without intravenous contrast that contained images (before any instrumentation) of the upper instrumented vertebral level., Outcome Measures: Reoperation for any reason (primary outcome) or a newly documented vertebral fracture (secondary outcome) occurring up to 5 years after the primary surgery., Methods: All study data were extracted using available coded information and CT scans from the medical records. BCT was performed at a centralized lab blinded to the clinical outcomes; patients could test positive for osteoporosis based on either low values of bone strength (vertebral strength ≤ 4,500 N women or 6,500 N men) and/or bone mineral density (vertebral trabecular bone mineral density ≤ 80 mg/cm 3 both sexes). Cox proportional hazard ratios were adjusted by age, presence of obesity, and whether the fusion was long (four or more levels fused) or short (3 or fewer levels fused); Kaplan-Meier survival was compared by the log rank test. This project was funded by NIH (R44AR064613) and all physician co-authors and author 1 received salary support from their respective departments. Author 6 is employed by, and author 1 has equity in and consults for, the company that provides the BCT test; the other authors declare no conflicts of interest., Results: For the 469 patients analyzed (298 women, 171 men), median follow-up time was 44.4 months, 11.1% had a reoperation (median time 14.5 months), and 7.7% had a vertebral fracture (median time 2.0 months). Overall, 25.8% of patients tested positive for osteoporosis and no patients under age 50 tested positive. Compared to patients without osteoporosis, those testing positive were at almost five-fold higher risk for vertebral fracture (adjusted hazard ratio 4.7, 95% confidence interval = 2.2-9.7; p<.0001 Kaplan-Meier survival). Of those positive-testing patients, those who tested positive concurrently for low values of both bone strength and bone mineral density (12.6% of patients overall) were at almost four-fold higher risk for reoperation (3.7, 1.9-7.2; Kaplan-Meier survival p<.0001); the remaining positive-testing patients (those who tested positive for low values of either bone strength or bone mineral density but not both) were not at significantly higher risk for reoperation (1.6, 0.7-3.7) but were for vertebral fracture (4.3, 1.9-10.2). For both clinical outcomes, risk remained high for patients who underwent short or long fusion., Conclusion: In a real-world clinical setting, BCT was effective in identifying primary spinal fusion patients aged 50 or older with osteoporosis who were at elevated risks of reoperation and vertebral fracture., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic necessitated a rapid adoption of telehealth (TH); however, its safety in subspecialty clinical practice remains uncertain. To assess the clinical outcomes associated with TH use in patients with coronary artery disease and/or heart failure during the initial phase of the COVID-19 pandemic, eligible adult patients who saw cardiologists from March 1, 2020, to August 31, 2020 (TH period) were identified. Patients were divided into two 3-month subcohorts (TH1, TH2) and compared with corresponding 2019 prepandemic subcohorts. The primary outcome was cardiovascular (CV) events within 3 months after index visits. Secondary analysis was CV events in patients aged ≥75 years within 3-month follow-up associated with TH use. Multivariable logistic regression was used to evaluate the association between TH use and CV outcomes. The study cohort included 6,485 TH and 7,557 prepandemic patients. The mean age was 70 years, with 40% of patients aged ≥75 years and 35% women. TH visits accounted for 0% of visits during the prepandemic period, compared with 68% during the TH period. Telephone visits comprised ≥92% of all TH encounters. Compared with the prepandemic period, patients seen during the TH period had fewer overall CV events (adjusted odds ratio 0.78, 95% confidence interval 0.67 to 0.90). Patients aged ≥75 years had similar findings (adjusted odds ratio 0.70, 95% confidence interval 0.55 to 0.89). Additional analysis of CV outcome events within 6 months after index visits showed similar findings. In conclusion, TH largely by way of telephone encounters can be safely incorporated into the ambulatory cardiology practice regardless of age., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Failure to follow up on patients with rectal bleeding is common and may result in a delay in diagnosis of colorectal cancer or in missing high-risk adenomas. The authors' purpose was to create an electronic patient safety net for those diagnosed with rectal bleeding but who did not have colonoscopy to ensure proper detection of colonic abnormalities, including colon cancer. Methods In an integrated health delivery system serving < 4.6 million patients in Southern California, from 2014 to 2019, the authors electronically identified patients with rectal bleeding aged 45 to 80 years but with no recently documented colonoscopy. These cases were reviewed by a gastroenterologist to determine if colonoscopy was appropriate. The physician looked for known documentation as to the cause of rectal bleeding and verified no contraindications to the procedure; if indicated, testing was offered. Results Using the authors' safety net program, 1430 patients with rectal bleeding who needed and completed a colonoscopy were identified. Of those patients, 7.5% had an advanced adenoma or cancer, with a total of 20 cancers, and 34% had findings that warranted more frequent colonoscopy. Conclusions The authors designed a safety net system that was able to capture information on patients with rectal bleeding who had not had a colonoscopy and detected in 34% colonic pathology that would have otherwise gone undetected. The program did not require many resources to implement and had the ability to potentially prevent harm from reaching patients whose rectal bleeding did not get prompt workup. Other health systems and practices should consider implementing a similar system.

This study highlights an unmet need in osteoporosis management, suggesting that beyond bone mineral density and fracture history, gender, fracture type, and age should be considered for fracture risk assessment. Following fragility fracture, men, patients with a spine or hip fracture, and those aged ≥ 65 have a higher disease burden., Introduction: The objective of this study was to characterize osteoporosis-related fracture incidence and identify predictors of subsequent fractures and mortality., Methods: This retrospective cohort study, conducted within Kaiser Permanente Southern California, included patients aged ≥ 50 years with qualifying fractures from 1/1/2007 to 12/31/2016, identified from diagnosis/procedure codes. Rates for fracture incidence, mortality, and resource utilization in the year post-fracture are reported. Associations between index fracture types and demographic/clinical characteristics, and mortality, subsequent fracture, and rehospitalization outcomes were estimated., Results: Of 63,755 eligible patients, 66.7% were ≥ 65 years and 69.1% female. Index fractures included nonhip/nonspine (64.4%), hip (25.3%), and spine (10.3%). Age-adjusted subsequent fracture rate/100 person-years was higher for those with an index spine (14.5) versus hip fracture (6.3). Hospitalization rate/100 person-years was highest for patients ≥ 65 (31.8) and for spine fractures (43.5). Men (vs women) had higher age-adjusted rates of hospitalization (19.4; 17.7), emergency room visits (73.8; 66.3), and use of rehabilitation services (31.7; 27.2). The 30-day age-adjusted mortality rate/100 person-years was 46.7, 32.4, and 15.5 for spine, hip, and nonspine/nonhip fractures. The 1-year age-adjusted mortality rate/100 person-years was 14.7 for spine and 15.6 for hip fractures. In multivariable analyses, spine and hip fractures (vs nonhip/nonspine fractures) were significant predictors of 1-year mortality, all-cause and osteoporosis-related hospitalization, and nursing home use (all P-values < 0.0001)., Conclusion: Morbidity is high in the year following a fragility fracture and men, patients with a spine or hip fracture, and those aged ≥ 65 have a greater disease burden., (© 2021. The Author(s).)

Bisphosphonates are effective in reducing hip and other fractures. However, concerns about atypical femur fractures (AFFs) have contributed to substantially decreased bisphosphonate use, and hip fracture rates may be increasing. Despite this impact, important uncertainties remain regarding AFF risks including the association between bisphosphonate use and other risk factors such as BMD, age, weight, and race. To address this evidence gap, a cohort study of 196,129 women ≥50 years of age in the Southern California Kaiser Permanente HMO women (with ≥1 bisphosphonate prescription) were studied; the primary outcome was radiographically-adjudicated AFF between 2007 and 2017. Risk factors including bisphosphonate use and race were obtained from electronic health records. Multivariable Cox models were used for analysis. Benefit-risk was modeled for 1-10 years of bisphosphonates to compare fractures prevented vs. AFFs associated. Among 196,129 women, 277 (0.1%) sustained AFFs. After multivariable adjustment, AFF risk increased with longer bisphosphonate duration: hazard ratio (HR) increased from HR = 8.9 (95%CI: 2.8,28) for 3-5 years to HR = 43.5 (13.7138.1) for >8 years. Hip BMD, surprisingly, was not associated with AFF risk. Other risk factors included Asian ancestry (HR = 4.8 (3.6, 6.6)), short stature, overweight, and glucocorticoid use. Bisphosphonate discontinuation was associated with rapid decrease in AFF risk. Decreases in osteoporotic and hip fractures risk during 1-10 years of bisphosphonates far outweighed the increase AFF risk in Caucasians, but less so in Asians. In Caucasians, after 3 years 149 hip fractures were prevented with 2 AFFs associated compared to 91 and 8 in Asians. The evidence for several potential mechanisms is summarized with femoral geometry being the most likely to explain AFF risk differences between Asians and Caucasians. The results from this new study add to the evidence base for AFF risk factors and will help inform clinical decision-making for individual patients about initiation and duration of bisphosphonate therapy and drug holidays., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The fungal genus Candida includes common commensals of the human mucosal membranes, and the most prevalently isolated species, C. albicans, poses a threat of candidemia and disseminated infection associated with an unacceptably high mortality rate and an immense $4 billion burden (US) yearly. Nevertheless, the demand for a vaccine remains wholly unfulfilled and increasingly pressing. We developed a double-peptide construct that is feasible for use in humans with the intention of preventing morbid infection by targeting epitopes derived from fructose bisphosphate aldolase (Fba) and methionine synthase (Met6) which are expressed on the C. albicans cell surface. To test the applicability of the design, we vaccinated mice via the intramuscular (IM) route with the conjugate denoted Fba-Met6 MP12 and showed that the vaccine enhanced survival against a lethal challenge. Because overall endpoint IgG1 and IgG2a antibody titers were robust and these mouse subclasses are associated with protective functionality, we investigated the potential of Fba and Met6 specific antibodies to facilitate the well-defined anti-Candida response by complement, which opsonizes fungi for degradation by primary effectors. Notably, reductions in the fungal burdens and enhanced survival were both abrogated in MP12-vaccinated mice that were pre-challenge dosed with cobra venom factor (CVF), a complement depleting factor. Altogether, we demonstrated that complement is relevant to MP12-based protection against disseminated C. albicans, delineating that a novel, multivalent targeted vaccine against proteins on the surface of C. albicans can enhance the natural response to infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Student-faculty (S-F) interactions that are conducive to students' learning can help reduce the retention and graduation gaps in higher education, especially for college students from underrepresented and underprivileged backgrounds. The aim of the study was to explore students' perceptions of their interactions with faculty, and the subjective impact of these interactions on students' academic and personal life. We analyzed qualitative data from a larger study with the goal of providing best practice models to support students experiencing displacement and food insecurity. Through purposive sampling techniques, 53 students from a diverse public university were recruited. Recruitment strategies focused on students who were likely to be facing academic, personal, and/or financial challenges that may affect their academic performance. Students were interviewed three to four times over a four to six-month period, using semi-structured interview guides. Our multidisciplinary team analyzed data thematically in team-based coding sessions using an online software. We identified four themes for faculty practices: (1) Creating Pedagogical Space, (2) Being Inclusive and Aware, (3) Being Engaged and Engaging Students, (4) Doing More Than Teaching. Based on students' perspectives, these practices lead to supportive and responsive S-F relationships that facilitate learning and success. The findings have implications related to how faculty can encourage caring S-F relationships and create conducive learning environments where students can thrive, especially during times of crisis., Competing Interests: Conflict of InterestThe authors declare that there are no conflicts of interest., (© The Author(s) 2020.)

Importance: Clinical trials have demonstrated the antifracture efficacy of bisphosphonate drugs for the first 3 to 5 years of therapy. However, the efficacy of continuing bisphosphonate for as long as 10 years is uncertain., Objective: To examine the association of discontinuing bisphosphonate at study entry, discontinuing at 2 years, and continuing for 5 additional years with the risk of hip fracture among women who had completed 5 years of bisphosphonate treatment at study entry., Design, Setting, and Participants: This cohort study included women who were members of Kaiser Permanente Northern and Southern California, 2 integrated health care delivery systems, and who had initiated oral bisphosphonate and completed 5 years of treatment by January 1, 2002, to September 30, 2014. Data analysis was conducted from January 2018 to August 2020., Exposure: Discontinuation of bisphosphonate at study entry (within a 6-month grace period), discontinuation at 2 years (within a 6-month grace period), and continuation for 5 additional years., Main Outcomes and Measures: The outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records., Results: Among 29 685 women (median [interquartile range] age, 71 [64-77] years; 17 778 [60%] non-Hispanic White individuals), 507 incident hip fractures were identified. Compared with bisphosphonate discontinuation at study entry, there were no differences in the cumulative incidence (ie, risk) of hip fracture if women remained on therapy for 2 additional years (5-year risk difference [RD], -2.2 per 1000 individuals; 95% CI, -20.3 to 15.9 per 1000 individuals) or if women continued therapy for 5 additional years (5-year RD, 3.8 per 1000 individuals; 95% CI, -7.4 to 15.0 per 1000 individuals). While 5-year differences in hip fracture risk comparing continuation for 5 additional years with discontinuation at 2 additional years were not statistically significant (5-year RD, 6.0 per 1000 individuals; 95% CI, -9.9 to 22.0 per 1000 individuals), interim hip fracture risk appeared lower if women discontinued after 2 additional years (3-year RD, 2.8 per 1000 individuals; 95% CI, 1.3 to 4.3 per 1000 individuals; 4-year RD, 9.3 per 1000 individuals; 95% CI, 6.3 to 12.3 per 1000 individuals) but not without a 6-month grace period to define discontinuation., Conclusions and Relevance: In this study of women treated with bisphosphonate for 5 years, hip fracture risk did not differ if they discontinued treatment compared with continuing treatment for 5 additional years. If women continued for 2 additional years and then discontinued, their risk appeared lower than continuing for 5 additional years. Discontinuation at other times and fracture rates during intervening years should be further studied.

Background: Falls and hip fractures among older people are associated with high morbidity and mortality. Hyponatraemia may be a risk for falls/hip fractures, but the effect of hyponatraemia duration is not well understood., Aims: To evaluate individuals with periods of sub-acute and chronic hyponatraemia on subsequent risk for serious falls and/or hip fractures., Methods: Retrospective cohort study in the period 1 January 1998 to 14 June 2016 within an integrated health system of individuals aged ≥55 years with ≥2 outpatient serum sodium measurements. Hyponatraemia was defined as sodium <135 mEq/L with sub-acute (<30 days) and chronic (≥30 days) analysed as a time-dependent exposure. Multivariable Cox proportional-hazards modelling was used to estimate hazard ratios (HR) for serious falls/hip fractures based on sodium category., Results: Among 1 062 647 individuals totalling 9 762 305 sodium measurements, 96 096 serious falls/hip fracture events occurred. Incidence (per-1000-person-years) of serious falls/hip fractures were 11.5, 27.9 and 19.8 for normonatraemia, sub-acute and chronic hyponatraemia. Any hyponatraemia duration compared to normonatraemia had a serious falls/hip fractures HR (95%CI) of 1.18 (1.15, 1.22), with sub-acute and chronic hyponatraemia having HR of 1.38 (1.33, 1.42) and 0.91 (0.87, 0.95), respectively. Examined separately, the serious falls HR was 1.37 (1.32, 1.42) and 0.92 (0.88, 0.96) in sub-acute and chronic hyponatraemia, respectively. Hip fracture HR were 1.52 (1.42, 1.62) and 1.00 (0.92, 1.08) for sub-acute and chronic hyponatraemia, respectively, compared to normonatraemia., Conclusions: Our findings suggest that early/sub-acute hyponatraemia appears more vulnerable and associated with serious falls/hip fractures. Whether hyponatraemia is a marker of frailty or a modifiable risk factor for falls remains to be determined., (© 2019 Royal Australasian College of Physicians.)

Backgroud: To determine patient factors that lead to treatment of meniscal tears with osteoarthritis (OA) with knee arthroscopy (KA) or physical therapy only (PT-only); and to assess differences in clinical outcomes including the time to knee arthroplasty., Methods: Patients aged ≥ 45 years with OA at meniscal tear diagnosis were followed up from the date of surgery (KA) or first PT visit (PT-only) until partial/total knee replacement surgery, death, disenrollment, or end of study. Demographic and clinical characteristics were compared and used to derive propensity scores. A Cox proportional hazards model was used to estimate the risk of knee replacement surgery and greater healthcare utilization associated with KA vs. PT-only., Results: Among 7,026 patients (KA, 69%; PT-only, 31%), 27% had partial or total knee replacement surgery during follow-up. PT-only patients were older and more likely to be women and had more comorbidities. After accounting for differences between groups, the cumulative incidence of knee replacement was modestly but significantly higher for those who received KA than those who underwent PT-only (hazard ratio, 1.30; 95% confidence interval, 1.17-1.44; p < 0.001), although there was no significant difference in health service utilization, narcotic medication dispenses, or knee injections after initiating treatment., Conclusions: For patients with meniscal damage complicated by OA, those who underwent KA were 30% more likely to have partial or total knee replacement surgery at any given time than those who had PT alone., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2020 by The Korean Orthopaedic Association.)