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SummaryThis 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.IntroductionThe objective of this study was to characterize osteoporosis-related fracture incidence and identify predictors of subsequent fractures and mortality.MethodsThis 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.ResultsOf 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).ConclusionMorbidity 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.

We conducted a retrospective cohort study in Kaiser Permanente Southern California from 1 January 2020 to 30 September 2020. We found that rituximab‐treated persons with multiple sclerosis (pwMS, n = 1895) were more likely be hospitalized (n = 8, 33.3%), but not die (n = 0) from COVID‐19, compared to the 4.81 million non‐MS population (5.8% and 1.4%, respectively). Time in months (adjusted OR = 0.32, 95% CI = 0.15–0.69, p = 0.0033) and receiving 1000 mg compared to lower doses at last infusion (adjusted OR = 6.28, 95% CI = 1.38–28.5, p = 0.0173) were independent predictors of COVID‐19 severity. Rituximab‐treated pwMS should be counseled to take extra precautions in the 5 months following each infusion. Using extended dosing intervals and lower doses could be considered.

In this study involving women 50 years of age or older who were receiving bisphosphonates, the risk of atypical femur fracture was very low as compared with the number of hip and other fractures that were prevented. Risk of atypical fractures increased with longer duration of bisphosphonate use and rapidly decreased after bisphosphonate discontinuation.

Objective To design and implement a health system level intervention to reduce escalating multiple sclerosis (MS) disease modifying treatment (DMT) expenditures and improve outcomes. Methods We conducted stakeholder meetings, reviewed pharmacy utilization data, and ed information in subsets of persons with MS (pwMS) from the electronic health record to identify gaps in, and barriers to improving, quality, and affordability of MS care in Kaiser Permanente Southern California. These results informed the development and implementation of the MS Treatment Optimization Program (MSTOP). Results The two main gaps identified were under‐prescribing of highly effective DMTs (HET, 4.9%) and the preferred formulary DMT (20.9%) among DMT‐treated pwMS. The main barriers identified were prescribers’ fear of rare but serious HET side effects, lack of MS‐specific and health systems science knowledge, Pharma influence, evidence gaps, formulary decisions‐based solely on costs, and multidirectional mistrust between neurologists, practice leaders, and health plan pharmacists. To overcome these barriers MSTOP developed four strategies: (1) risk‐stratified treatment algorithm to increase use of HETs; (2) an expert‐led ethical, cost‐sensitive, risk‐stratified, preferred formulary; (3) proactive counter‐launch campaigns to minimize uptake of new, low‐value DMTs; and (4) discontinuation of ineffective DMTs in progressive, non‐relapsing MS. The multicomponent MSTOP was implemented through education, training, and expanding access to MS‐trained providers, audit and feedback, and continual evidence reviews. Interpretation The causes of wasteful spending on MS DMTs are complex and require multiple strategies to resolve. We provide herein granular details of how we designed and implemented our health system intervention to facilitate its adaption to other settings and conditions.

To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer–specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.

Rituximab and other B-cell-depleting therapies blunt humoral responses to SARS-CoV-2 vaccines, particularly when the vaccine is administered within 6 months of an infusion. Whether this translates into an increased risk of hospitalization or death from COVID-19 is unclear. To examine whether rituximab treatment is associated with an increased risk of hospitalization for COVID-19 among SARS-CoV-2-vaccinated persons with multiple sclerosis (MS) and whether delaying vaccination more than 6 months after rituximab treatment is associated with decreased risk. This retrospective cohort study used Kaiser Permanente Southern California's electronic health record to identify individuals from January 1, 2020, to February 15, 2022, who had MS and who had been vaccinated against SARS-CoV-2. Rituximab treatment compared with disease-modifying therapies (DMTs) that do not interfere with vaccine efficacy or being untreated (no or other DMT group). Among rituximab-treated patients, the exposure was receiving at least 1 vaccine dose more than 6 months after their last infusion compared with receiving all vaccine doses 6 months or less since their last infusion. The main outcome was hospitalization due to COVID-19 infection. The odds of infection resulting in hospitalization following SARS-CoV-2 vaccination were adjusted for race and ethnicity, advanced MS-related disability; vaccine type; booster dose; and, among rituximab-treated only analyses, cumulative rituximab dose and dose at last infusion. Exposures, outcomes, and covariates were collected from the electronic health record. Among 3974 SARS-CoV-2-vaccinated people with MS (mean [SD] age, 55.3 [15] years; 2982 [75.0%] female; 103 [2.6%] Asian or Pacific Islander; 634 [16.0%] Black; 953 [24.0%] Hispanic; 2269 [57.1%] White; and 15 [0.3%] other race or ethnicity), rituximab-treated patients (n = 1516) were more likely to be hospitalized (n = 27) but not die (n = 0) compared with the 2458 individuals with MS receiving no or other DMTs (n = 7 and n = 0, respectively; adjusted odds ratio [aOR] for hospitalization, 7.33; 95% CI, 3.05-17.63). Receiving messenger RNA (mRNA) SARS-CoV-2 vaccine (aOR, 0.36; 95% CI, 0.15-0.90; P = .03) and receiving a booster vaccination (aOR, 0.31; 95% CI, 0.15-0.64; P = .002) were independently associated with a decreased risk of hospitalization for COVID-19. Among vaccinated rituximab-treated individuals with MS, receiving any vaccination dose more than 6 months after the last rituximab infusion was associated with a reduced risk of COVID-19 hospitalization (aOR, 0.22; 95% CI, 0.10-0.49). This cohort study's findings suggest that rituximab-treated people with MS should be strongly encouraged to receive mRNA SARS-CoV-2 vaccines and boosters more than 6 months after their last rituximab infusion whenever possible. The low absolute risk of hospitalization for COVID-19 among mRNA-vaccinated individuals with MS should not preclude use of rituximab, which has marked efficacy, cost, and convenience advantages over other DMTs.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 personyears [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Aims/hypothesis The aim of this study was to assess and compare risks of having large- or small-for gestational age (LGA and SGA, respectively) infants born to women with gestational diabetes mellitus (GDM) from ten racial/ethnic groups. Methods LGA and SGA were defined as birthweight >90th and <10th percentile, respectively, specific to each racial/ethnic population and infant sex. Risks of LGA and SGA were compared among a retrospective cohort of 29,544 GDM deliveries from Hispanic, non-Hispanic white (NHW), non-Hispanic black (NHB), Filipino, Chinese, Asian Indian, Vietnamese, Korean, Japanese and Pacific Islander (PI) groups of women. Results Unadjusted LGA and SGA risks varied among the ten groups. For LGA, the highest risk was in infants born to NHB women (17.2%), followed by those born to PI (16.2%), Hispanic (14.5%), NHW (13.1%), Asian Indian (12.8%), Filipino (11.6%) and other Asian (9.6–11.1%) women ( p  < 0.0001). Compared with NHW, the LGA risk was significantly greater for NHB women with GDM (RR 1.25 [95% CI 1.11–1.40]; p  = 0.0001 after adjustment for maternal characteristics). Further adjustment for maternal pre-pregnancy BMI and gestational weight gain in the sub-cohort with available data ( n  = 8,553) greatly attenuated the elevated LGA risk for NHB women. For SGA, the risks ranged from 5.6% to 11.3% ( p  = 0.003) where most groups (8/10) had risks that were lower than the population-expected 10% and risks were not significantly different from those in NHW women. Conclusions/interpretation These data suggest that variation in extremes of fetal growth associated with GDM deliveries across race/ethnicity can be explained by maternal characteristics, maternal obesity and gestational weight gain. Women should be advised to target a normal weight and appropriate weight gain for pregnancies; this is particularly important for NHB women.

To assess associations between race/ethnicity, glycated hemoglobin (HbA1c), and glycemic control among youth with type 1 (T1D) or type 2 diabetes (T2D). The study sample was youth<20years old from the SEARCH California Center diagnosed from 2002 to 2009 who remained insured for at least one year. HbA1c at one year was from clinical data; HbA1c at diagnosis was from clinical data (81%) or imputed (19%). Multivariable logistic and linear regression models were used to examine associations between race/ethnicity and poor glycemic control (≥9.5%), HbA1c at one-year, and change in HbA1c. The study included 1162 Hispanic (52.3%), non-Hispanic White (NHW, 28.4%), African American (15.1%) and Asian/Pacific Islander (4.1%) youth. Among T1D youth (n=789), Hispanics were 1.60 times as likely (95% CI 1.01–2.53) to have poor control at one year compared to NHWs, after adjustments. Among T2D youth (n=373), only African American youth were significantly more likely (OR=4.85; 95% CI 1.49–15.77) to have poor control at one year, after adjustments. HbA1c at one year and change in HbA1c did not differ by race/ethnicity. Poor glycemic control was evident one year after diagnosis in some minority youth with T1D or T2D in an integrated managed health care setting.

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. 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. 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. 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. The outcome was hip fracture determined by principal hospital discharge diagnoses. Demographic, clinical, and pharmacological data were ascertained from electronic health records. 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. 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.