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Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Author/s: 
Bojana Petek, Henrike Häbel, Hong Xu, Marta Villa-Lopez, Irena Kalar, Minh Tuan Hoang, Silvia Maioli, Joana B Pereira, Shayan Mostafaei, Bengt Winblad, Milica Gregoric Kramberger, Maria Eriksdotter, Sara Garcia-Ptacek

Background
Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.

Objective
To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.

Methods
A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.

Results
Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.

Conclusions
Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses

Keywords 
alzheimer's disease Cholesterol metabolism Cognitive impairment cohort study HMG-CoA reductase inhibitors statins

Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl

Author/s: 
Chambers, Laura C., Hallowell, benjamin D., Zullo, Andrew R.

Question: Are higher doses of buprenorphine treatment for opioid use disorder associated with improved retention in treatment when use of fentanyl (vs heroin) is more prevalent?

Findings: In this cohort study of 6499 patients initiating buprenorphine treatment between 2016 and 2020, those prescribed the recommended daily dose (16 mg) were at significantly greater risk of treatment discontinuation within 180 days than those prescribed a higher dose (24 mg).

Meaning: The results of this study suggest that the value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.

Keywords 
cohort study Opiod use disorder fentanyl

Do carotid artery calcifications seen on radiographs predict stenosis in asymptomatic adults?

Author/s: 
Cowdrey, D., Hahn, T. W., Vellardita, L.

EVIDENCE-BASED ANSWER:
NOT VERY WELL. IN ASYMPTOMATIC PATIENTS, CAROTID ARTERY CALCIFICATION SEEN ON RADIOGRAPH HAS A POSITIVE PREDICTIVE VALUE OF 70% AND A NEGATIVE PREDICTIVE VALUE OF 75% FOR CAROTID ARTERY STENOSIS (STRENGTH OF RECOMMENDATION [SOR]: B, SYSTEMATIC REVIEW OF OBSERVATIONAL STUDIES WITH HETEROGENEOUS RESULTS AND A RETROSPECTIVE COHORT STUDY). CAROTID CALCIFICATIONS ON RADIOGRAPHS MAY BE MORE PREDICTIVE OF CAROTID STENOSIS IN PEOPLE WITH ATHEROSCLEROTIC RISK FACTORS (SOR: C, CROSS-SECTIONAL STUDY). HARMS OUTWEIGH BENEFITS IN SCREENING FOR CAROTID ARTERY STENOSIS IN ASYMPTOMATIC ADULTS (SOR: B, MULTIPLE COHORT STUDIES); THEREFORE, INCIDENTAL RADIOGRAPHIC CAROTID ARTERY CALCIFICATIONS IN ASYMPTOMATIC PATIENTS SHOULD NOT PROMPT FURTHER TESTING.

Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure

Author/s: 
Izurieta, H. S., Wu, X., Forshee, R., Lu, Y., Sung, H. M., Agger, P. E., Chillarige, Y., Link-Gelles, R., Lufkin, B., Wernecke, M., MaCurdy, T. E., Kelman, J., Dooling, K.

Background
Shingrix (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as 2 doses given 2–6 months apart among adults aged ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster, but post-market performance has not been evaluated. Efficacy of a single dose and a delayed second dose and efficacy among persons with autoimmune or immunosuppressive conditions have not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix.

Methods
We conducted a cohort study among Medicare Part D community-dwelling beneficiaries aged >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia was identified using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance and marginal structural models to estimate hazard ratios.

Results
We found a vaccine effectiveness of 70.1% (95% confidence interval [CI], 68.6–71.5) and 56.9% (95% CI, 55.0–58.8) for 2 and 1 doses, respectively. The 2-dose vaccine effectiveness was not significantly lower for beneficiaries aged >80 years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4–81.8).

Conclusions
This large real-world observational study of the effectiveness of Shingrix demonstrates the benefit of completing the 2-dose regimen. Second doses administered beyond the recommended 6 months did not impair effectiveness. Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.

Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk

Author/s: 
Shavit, R., Maoz-Segal, R., Iancovici-Kidon, M.

Importance
Allergic reactions among some individuals who received the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine discourage patients with allergic conditions from receiving this vaccine and physicians from recommending the vaccine.

Objective
To describe the assessment and immunization of highly allergic individuals with the BNT162b2 vaccine.

Design, Setting, and Participants
In a prospective cohort study from December 27, 2020, to February 22, 2021, 8102 patients with allergies who applied to the COVID 19 vaccine referral center at the Sheba Medical Center underwent risk assessment using an algorithm that included a detailed questionnaire. High-risk patients (n = 429) were considered “highly allergic” and were immunized under medical supervision.

Exposures
Pfizer-BioNTech (BNT162b2) COVID-19 vaccine.

Main Outcomes and Measures
Allergic and anaphylactic reactions after the first and second doses of BNT162b2 vaccine among highly allergic patients.

Results
Of the 429 individuals who applied to the COVID-19 referral center and were defined as highly allergic, 304 (70.9%) were women and the mean (SD) age was 52 (16) years. This highly allergic group was referred to receive immunization under medical supervision. After the first dose of the BNT162b2 vaccine, 420 patients (97.9%) had no immediate allergic event, 6 (1.4%) developed minor allergic responses, and 3 (0.7%) had anaphylactic reactions. During the study period, 218 highly allergic patients (50.8%) received the second BNT162b2 vaccine dose, of which 214 (98.2%) had no allergic reactions and 4 patients (1.8%) had minor allergic reactions. Other immediate and late reactions were comparable with those seen in the general population, except for delayed itch and skin eruption, which were more common among allergic patients.

Conclusions and Relevance
The rate of allergic reactions to BNT162b2 vaccine, is higher among patients with allergies, particularly among a subgroup with a history of high-risk allergies. This study suggests that most patients with a history of allergic diseases and, particularly, highly allergic patients can be safely immunized by using an algorithm that can be implemented in different medical facilities and includes a referral center, a risk assessment questionnaire, and a setting for immunization under medical supervision of highly allergic patients. Further studies are required to define more specific risk factors for allergic reactions to the BNT162b2 vaccine.

Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis

Author/s: 
Renaud, Marion, Thibault, Claire, Normand, F. L., Mcdonald, E. G., Gallix, B., Debry, C., Venkatasamy, A.

Since the pandemic was declared in early 2020, COVID-19–related anosmia quickly emerged as a telltale sign of infection.1,2 However, the time course and reversibility of COVID-19–related olfactory disorders, which may persist and negatively affect patients’ lives, require further study. To clarify the clinical course and prognosis, we followed a cohort of patients with COVID-19–related anosmia for 1 year and performed repeated olfactory function evaluations for a subset of patients.

Keywords 
COVID-19 Anosmia diagnosis Infection clinical outcomes

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication

Author/s: 
Schaefer, J. K., Errickson, J., Li, Y., Kong, X., Alexandris-Souphis, T., Ali, M. A., Decamillo, D., Haymart, B., Kaatz, S., Kline-Rogers, E., Kozlowski, J. H., Krol, G. D., Shankar, S, R., Sood, S. L., Froehlich, J. B., Barnes, G. D.

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes.

Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE).

Design, setting, and participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up.

Exposures: Use of ASA concomitant with DOAC therapy.

Main outcomes and measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death.

Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02).

Conclusion and relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

Keywords 
aspirin anticoagulant therapy treatment heart-valve replacement thrombosis

Association of metabolic–bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174772 participants

Author/s: 
Syn, N.L, Cummings, D. E., Wang, L. Z., Lin, D. J., Zhao, J. J., Loh, M., Koh, Z. J., Chew, C. A., Kim, G., Bok-Yan So, J., Kaplan, L. M., Dixon, J. B., Shabbir, A.

Summary Background Metabolic–bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy—especially stratified by pre-existing diabetes status—are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic–bariatric surgery versus usual care. Methods We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic–bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic–bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472. 

Keywords 
gastric bypass obesity proportional hazard models bariatric surgery gastrectomy weight loss

Cancer Prevalence and Risk Stratification in Adults Presenting With Hematuria: A Population-Based Cohort Study

Author/s: 
Takeuchi, Mitsuru, McDonald, Jennifer S., Takahashi, Naoki, Frank, Igor, Thompson, R. H., King, Bernard F., Kawashima, Akira

Abstract

Objective

To calculate the prevalence of renal cell carcinoma (RCC), upper urinary tract urothelial carcinoma (UT-UC), and lower urinary tract urothelial carcinoma (LT-UC) in patients with gross asymptomatic microhematuria (AMH) and symptomatic microhematuria (SMH).

Patients and Methods

This study was a population-based retrospective descriptive study. The study was approved by both the Mayo Clinic Institutional Review Board and the Olmsted Medical Center Institutional Review Board, and the population used was Olmsted County residents. A total of 4453 patients who presented with an initial episode of hematuria from January 1, 2000, through December 30, 2010, were included. Of the 4453 patients (median age, 58 years; interquartile range, 44.6-73.3 years), 1487 (33.4%) had gross hematuria, 2305 (51.8%) had AMH, and 661 (14.8%) had SMH.

Results

In the 1487 patients with gross hematuria, the prevalence of RCC, UT-UC, and LT-UC was 1.3%, 0.8%, and 9.0%, respectively. In the 2305 patients with AMH, the prevalence of RCC, UT-UC, and LT-UC was 0.2%, 0.3%, and 1.6%, respectively. In the 661 patients with SMH, the prevalence of RCC, UT-UC, and LT-UC was 0.6%, 0.2%, and 0.3%, respectively. Age was the most relevant risk factor for any hematuria type.

Conclusion

This unique cohort study reported that the prevalence of RCC or UC in patients with AMH and SMH was low, especially in the young cohort, and a large number of intense work-ups, such as cystoscopy and computed tomography urography, currently conducted could be omitted if stratified by hematuria type and age.

Keywords 
cancer Hematuria Adults RCC Carcinoma, Renal Cell

Glucosamine/Chondroitin and Mortality in a US NHANES Cohort

Author/s: 
King, Dana E., Xiang, Jun

Background: Limited previous studies in the United Kingdom or a single US state have demonstrated an association between intake of glucosamine/chondroitin and mortality. This study sought to investigate the association between regular consumption of glucosamine/chondroitin and overall and cardiovascular (CVD) mortality in a national sample of US adults.

Methods: Combined data from 16,686 participants in National Health and Nutrition Examination Survey 1999 to 2010, merged with the 2015 Public-use Linked Mortality File. Cox proportional hazards models were conducted for both CVD and all-cause mortality.

Results: In the study sample, there were 658 (3.94%) participants who had been taking glucosamine/chondroitin for a year or longer. During followup (median, 107 months), there were 3366 total deaths (20.17%); 674 (20.02%) were due to CVD. Respondents taking glucosamine/chondroitin were less likely to have CVD mortality (hazard ratio [HR] = 0.51; 95% CI, 0.28-0.92). After controlling for age, use was associated with a 39% reduction in all-cause (HR = 0.61; 95% CI, 0.49-0.77) and 65% reduction (HR = 0.35; 95% CI, 0.20-0.61) in CVD mortality. Multivariable-adjusted HR showed that the association was maintained after adjustment for age, sex, race, education, smoking status, and physical activity (all-cause mortality, HR = 0.73; 95% CI, 0.57-0.93; CVD mortality, HR = 0.42; 95% CI, 0.23-0.75).

Conclusions: Regular intake of glucosamine/chondroitin is associated with lower all-cause and CVD mortality in a national US cohort and the findings are consistent with previous studies in other populations. Prospective studies to confirm the link may be warranted.

Keywords 
Chondroitin Cardiovascular Diseases Glucosamine Cohort Studies Nutrition Surveys osteoarthritis Proportional Hazards Models
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