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Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications.A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine.None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).

ImportanceMedicare Advantage is associated with improved health outcomes, increased care efficiency, and lower out-of-pocket costs compared with fee-for-service (FFS) Medicare. When engaged in 2-sided risk arrangements, physicians are incented to offer high value for patients; however, no studies have explored the quality and efficiency outcomes in 2-sided risk Medicare Advantage models compared with FFS Medicare.ObjectiveTo compare quality and efficiency of care between physicians using a Medicare Advantage 2-sided risk model and FFS Medicare.Design, Setting, and ParticipantsThis retrospective cohort analysis with exact and propensity score–matched design used claims data from January 1, 2018, to December 31, 2019. Participants included beneficiaries enrolled in a Medicare Advantage 2-sided risk model (ie, physicians assumed the financial risk of total costs of care) and those in an FFS Medicare program in a 5% limited data set with part A and B coverage residing in 6 states (Arizona, California, Florida, Nevada, Texas, and Utah). Data were analyzed from February 1 to June 15, 2022.ExposuresMedicare Advantage 2-sided risk model seen in practices that are part of a nationwide health care delivery organization compared with traditional FFS Medicare.Main Outcomes and MeasuresComparative analysis of 8 quality and efficiency metrics in populations enrolled in a 2-sided risk-model Medicare Advantage program and 5% FFS Medicare.ResultsIn this analytic cohort of 316 312 individuals (158 156 in each group), 46.11% were men and 53.89% were women; 32.72% were aged 65-69 years, 29.44% were aged 70-74 years, 19.05% were aged 75-79 years, 10.84% were aged 80-85 years, and 7.95% were 85 years or older. The Medicare Advantage model was associated with care of higher quality and efficiency in all 8 metrics compared with the FFS model. This included lower odds of inpatient admission (−18%; odds ratio [OR], 0.82 [95% CI, 0.79-0.84]), inpatient admission through the emergency department (ED) (−6%; OR, 0.94 [95% CI, 0.91-0.97]), ED visits (−11%; OR, 0.89 [95% CI, 0.86-0.91]), avoidable ED visits (−14%; OR, 0.86 [95% CI, 0.82-0.89]), 30-day inpatient readmission (−9%; rate ratio, 0.91 [95% CI, 0.86-0.98]), admission for stroke or myocardial infarction (−10%; OR, 0.90 [95% CI, 0.83-0.98]), and hospitalization for chronic obstructive pulmonary disease or asthma exacerbation (−44%; OR, 0.56 [95% CI, 0.50-0.62]).Conclusions and RelevanceThe improvements observed in this study may be partly or fully attributed to the Medicare Advantage model. The Medicare Advantage risk adjustment system appears to be meeting its intended goal by aligning the capitation payments to the health care burden of the individual beneficiary and aggregate population served, thus providing revenue to develop infrastructure that supports improvements in quality and efficiency for the patients enrolled in Medicare Advantage models with 2-sided risk.

Background: Cerebral venous sinus thrombosis (CVST) secondary to vaccine-induced thrombotic thrombocytopenia is an extremely rare side effect of adenovirus-based COVID-19 vaccines. CVST incidence associated with COVID-19 itself has not been widely reported. We report the incidence of CVST in patients hospitalized with COVID-19 during the first year of the pandemic. Methods: We analyzed de-identified electronic medical records of a retrospective cohort of patients admitted with COVID-19 to >200 hospitals between March 2020 and March 2021. We used International Classification of Diseases, Tenth Revision codes and natural language processing extracts to identify patients with a new CVST diagnosis during COVID-19 hospitalization. The primary outcome was CVST incidence in hospitalized, COVID-19-positive patients. Secondary outcomes included CVST incidence and mortality. Incidence rates were calculated using the DerSimonian-Laird estimator method. Results: Ninety-one thousand seven hundred twenty-seven patients were evaluated; 22 had new CVST diagnoses by electronic medical record review. CVST incidence in the hospitalized COVID-19 cohort was 231 per 1 000 000 person-years (95% CI, 152.1–350.8). FemalesP =0.012) and males (44.4% of males versus 7.7% of females, P =0.023) were more likely to die in hospital. Conclusions: CVST incidence in COVID-19–positive hospitalized patients is high. Advanced age and male gender were associated with likelihood of death in hospital; further studies are required to confirm these findings.

To understand primary care visits and medication utilization among older patients with hypertension to gauge opportunity for service redesign.Data came from 1,880,331 Medicare Advantage members with hypertension who had a primary care visit and a pharmacy claim for an antihypertensive, antidiabetic, or antilipemic medication. To determine activities associated with a primary care visit, we analyzed 43,258,454 medical claims, 245 procedure codes, and medication management associated with those visits. Models for predicting both hypertension visits and medication management were evaluated and applied.Logistic regression was used to identify which features were predictive of a medication change or a provider visit.Almost 40% of visits were consultation only, not associated with a procedure, and 26.5% of individuals had no medication change in a year. For prescription changes, 75% were a return to a previously prescribed medication or a medication discontinuation. Twenty percent of the population accounted for 47.9% of visits. Type 2 diabetes and a prior medication change were the strongest predictors of a medication change. A previous medication change was also the strongest predictor of a subsequent provider visit.Our analysis suggests that a significant portion of care-consultation-only visits-may be relatively low value. Further, much of medication management may not require an office-based visit. Finally, utilization behavior of patients with hypertension and predictive models are likely to allow informed provisioning of new service models to specific population segments.

Real-world analysis of the incidence of SARS-CoV-2 infection post vaccination is important in determining the comparative effectiveness of the available vaccines. In this retrospective cohort study using deidentified administrative claims for Medicare Advantage and commercially insured individuals in a research database we examine over 3.5 million fully vaccinated individuals, including 8,848 individuals with SARS-CoV-2 infection, with a follow-up period between 14 and 151 days after their second dose. Our primary outcome was the rate of Covid-19 infection occurring at 30, 60, and 90 days at least 14 days after the second dose of either the mRNA-1273 vaccine or the BNT162b2 vaccine. Sub-analyses included the incidence of hospitalization, ICU admission, and death/hospice transfer. Separate analysis was conducted for individuals above and below age 65 and those without a prior diagnosis of Covid-19. We show that immunization with mRNA-1273, compared to BNT162b2, provides slightly more protection against SARS-CoV-2 infection that reaches statistical significance at 90 days with a number needed to vaccinate of >290. There are no differences in vaccine effectiveness for protection against hospitalization, ICU admission, or death/hospice transfer (aOR 1.23, 95% CI (0.67, 2.25)).

One-third of health care in the United States is wasted. Despite this recognition, solutions are sparse. The Optimal Care model combines evidence-based medicine, patient-centered technology, and outcomes reporting to transform health care.

VISUAL ABSTRACT

Individuals with substance use disorders (SUDs). including co-occurring disorders, are among the highest-risk populations for medical and psychiatric rehospitalizations, and are often underdiagnosed at initial hospitalization. This study examined predictors for these individuals at baseline hospitalization and subsequent rehospitalizations. Three groups were compared from a sample of individuals admitted to inpatient psychiatry (1982 to 1987) with at least one rehospitalization within a 16-year period. Multivariate logistical regressions were used to determine associations with predictor variables. The data showed that individuals’ diagnosed with a SUD after baseline hospitalization were more likely to have more medical hospitalizations and to be diagnosed with schizophrenia compared to those who were diagnosed with a SUD, including co-occurring disorders, at baseline. The results of this study indicate the importance of substance use screening to enhance service resources and treatment outcomes for medically and psychiatrically complex populations.

The treatment of brain tumors in very young children poses both a therapeutic challenge and a bioethical quandary. The administration of craniospinal radiation after surgery offers the greatest chance for cure but causes severe neurocognitive damage. As a result, current practice does not offer parents the option of full-dose post-operative craniospinal radiation. Some may regard this approach as inappropriate medical paternalism, while others may consider it an example of responsible therapeutics. Evaluation of this dilemma reveals principles which can guide clinicians in determining which treatment options to present to their patients or surrogates, in the context of shared medical decision-making.

An estimated half of all women aged older than 50 yr will have an osteoporosis-related fracture in their lifetime. National osteoporosis clinical guidelines for screening recommend measurement of bone mineral density in average risk women beginning at age 65 yr. Little data are available regarding compliance with this recommendation. The objective of this study was to evaluate osteoporosis screening rates in a random sample of women, aged 66 yr or older, in a large multisite primary-care group practice. The study was conducted in a primary-care group practice serving over 180,000 patients in the Denver metropolitan area. Medical records of a random sample of 833 female patients aged 66 yr or older were reviewed retrospectively. Patients were seen at 1 of 13 practice locations, by 1 of 34 physicians, who practiced either family medicine or internal medicine. The frequency of osteoporosis screening was calculated. Accepted methods of screening include peripheral bone density measurement by ultrasound or dual-energy X-ray absorptiometry (DXA), or central DXA. The physician-specific osteoporosis screening rates varied widely, ranging from 19% to 97%. The practice-specific osteoporosis screening rates ranged from 26% to 91%. Overall, the mean rate of osteoporosis screening among all physicians was 56%. Despite improvements in osteoporosis screening, there continues to be a gap in the quality of care provided compared to national recommended guidelines. Policy changes, performance improvement measures, and interventions are needed to improve screening rates in primary-care practices.

Four experiments assessed the importance of stimulus number, repetition rate, and duration for newborns’ head orientation toward brief sounds and related those parameters to the critical ones found for adults. Infants’ responses to various trains of repeated 14-ms rattle sounds were compared with those to a 10-s rattle sound, known to elicit head orientation. Directional responses did not differ from the standard when rattle bursts were repeated at a rate of 20 per second for 1 s (experiment 1). Responding did differ from the standard and deteriorated to chance levels when either the number of moderately paced (6/s) stimulus bursts was decreased to six or fewer (experiments 2 and 3) or the duration of rapidly repeated (24/s) bursts was shortened to 500 ms (experiments 4A and 4B). These results suggest that newborns’ head orientation depends, in part, upon the number of stimulus bursts and stimulus duration.

The long-term follow-up of 21 patients who had undergone bilateral adrenalectomy for Cushing's disease has revealed eight definite and two suspected cases of pituitary tumors. The average time from adrenalectomy to the diagnosis of the pituitary tumor was 6 1/2 years, with a range of 1 1/2 to 12 years. The incidence of tumors in this study (38%) is higher than that reported by others and may reflect (1) that none of these patients received pituitary irradiation in addition to adrenalectomy, (2) the length of follow-up, and (3) the high index of suspicion and early diagnosis of pituitary tumors in recent years. These data raise the question of whether bilateral adrenalectomy alone is an acceptable form of therapy for Cushing's disease. For patients treated in this way, a life-long commitment should be made to undergo annual reexamination for the possible occurrence of a pituitary neoplasm. (Arch Intern Med138:575-579, 1978)

The availability of radioimmunoassay procedures for the measurement of thyroid-stimulating hormone (TSH) has simplified the differential diagnosis of primary vs secondary hypothyroidism. An elevation of the serum TSH level points to primary failure of the thyroid gland as the basis of the hypothyroidism. However, primary hypothyroidism may secondarily affect a variety of aspects of pituitary function, so that clinical tests evaluating pituitary hormone secretion may lose their diagnostic value. 1 Impaired secretion of growth hormone, delayed gonadotropin responses to luteinizing hormone-releasing factor, decreased adrenocorticotropic hormone release, and increased basal and stimulated prolactin levels have been reported in primary hypothyroidism. 1 Two additional findings that may be of particular clinical importance are the occurrence of amenorrhea-galactorrhea 2 and sellar enlargement, suggesting the presence of a pituitary tumor. 3 The term "amenorrhea-galactorrhea syndrome" has taken on a new meaning in recent years. Increasingly sophisticated endocrine, radiological, and neurosurgical skills have decreased the

Human peripheral blood lymphocytes were obtained from patients with MS and from healthy controls. Comparisons were made between the adherence of lymphocytes from donors of varying ages to myelin from donors of different age groups at the time of death. The adherence of control lymphocytes was maximum with lymphocytes from donors in their 30s. No obvious maximum for lymphocyte age was found for adherence of MS lymphocytes. However, MS adherence levels were significantly higher than control levels at most ages tested. Maximum adherence levels were observed for both MS and control cells with myelin from donors who were 20 to 45 years of age at the time of death. No significant difference between MS and control adherence to myelin from elderly donors was observed. Possible age-related changes in myelin and the relationship of maximum adherence to the peak age of onset of MS is discussed.