Risk of Developing alzheimer\u27s Disease and Related Dementias in allhat Trial Participants Receiving Diuretic, ace-inhibitor, or Calcium-Channel Blocker With 18 Years of Follow-Up

BACKGROUND: There is no any large randomized clinical trial of antihypertensive drug treatment with 18-year passive follow-up to examine the risk of Alzheimer\u27s Disease (AD) or Related Dementias (ADRD). METHODS: Post-trial passive follow-up study of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants in 1994-1998 by linking with their Medicare claims data through 2017 among 17,158 subjects in 567 U.S. centers who were free of ADRD at baseline on January 1, 1999. Main outcome was the occurrence of ADRD over 18 years of follow-up. RESULTS: The 18-year cumulative incidence rates were 30.9% for AD, 59.2% for non-AD dementias, and 60.9% for any ADRD. The 18-year cumulative incidence of AD was almost identical for the 3 drug groups (30.5% for chlorthalidone, 31.1% for amlodipine, and 31.4% for lisinopril). The hazard ratios of AD, non-AD dementias and total ADRD were not statistically significantly different among the 3 drug groups. The adjusted hazard ratio of AD was 1.04 (95% CI: 0.94-1.14) for chlorthalidone CONCLUSION: The risk of ADRD did not vary significantly by 3 antihypertensive drugs in ALLHAT trial participants with 18-years of follow-up. The risk of ADRD was significantly associated with age, gender, race/ethnicity, education, and history of vascular diseases

Mortality and Morbidity among individuals With Hypertension Receiving a Diuretic, ace inhibitor, or Calcium Channel Blocker: a Secondary analysis of a Randomized Clinical Trial

IMPORTANCE: The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood. OBJECTIVE: to determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up. DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N = 32 804) and morbidity outcomes (n = 22 754). Statistical analysis was performed from January 2022 to October 2023. INTERVENTIONS: Participants were randomly assigned to receive a thiazide-type diuretic (n = 15 002), a CCB (n = 8898), or an ACE inhibitor (n = 8904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years. MAIN OUTCOMES AND MEASURES: The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer. RESULTS: A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]). CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000542

Is There Any Role for Opioids in the Management of Knee and Hip Osteoarthritis? A Systematic Review and Meta‐Analysis

Objective: Opioids have long been prescribed for chronic pain conditions, including osteoarthritis (OA). However, there is little information about their temporal efficacy, or differences in efficacy and safety between opioids with strong versus weak/intermediate μ opioid receptor–binding affinity. To explore these research questions, we conducted a systematic review and meta-analyses of randomized controlled trials (RCTs) conducted in patients with knee and/or hip OA. Methods: We searched Medline, Embase, PubMed Central, and the Cochrane Central Register of Controlled Trials from inception to December 2019 and sought unpublished data. Placebo-controlled RCTs of oral opioids in patients with knee and/or hip OA were included. Standardized mean differences (SMDs) were calculated for pain and function at 2, 4, 8, and 12 weeks. Subgroup analyses for strong and weak/intermediate opioids were conducted. Meta-regression was performed to assess the impact of dosage (morphine equivalency) on pain relief. Risk ratios were calculated for safety at the final follow-up. Results: A total of 18 RCTs (9,283 participants) were included. Opioids demonstrated small benefits on pain at each time point, with SMDs ranging from –0.28 (95% confidence interval [95% CI] –0.38, –0.17) to –0.19 (95% CI –0.29, –0.08); similar effects were observed for function. Strong opioids demonstrated consistently inferior efficacy and overall worse safety than weak/intermediate opioids. Meta-regression revealed that incremental pain relief achieved beyond 20–50-mg doses was not substantial in the context of increased safety risks. Conclusion: Opioids provide minimal relief of OA symptoms within a 12-week period, and they are known to cause discomfort in a majority of patients. Clinicians and policy makers should reconsider the utility of opioids in the management of OA

Is There Any Role for Opioids in the Management of Knee and Hip Osteoarthritis? A Systematic Review and Meta-Analysis

Objective: Opioids have long been prescribed for chronic pain conditions, including osteoarthritis (OA). However, there is little information about their temporal efficacy, or differences in efficacy and safety between opioids with strong versus weak/intermediate μ opioid receptor–binding affinity. To explore these research questions, we conducted a systematic review and meta-analyses of randomized controlled trials (RCTs) conducted in patients with knee and/or hip OA. Methods: We searched Medline, Embase, PubMed Central, and the Cochrane Central Register of Controlled Trials from inception to December 2019 and sought unpublished data. Placebo-controlled RCTs of oral opioids in patients with knee and/or hip OA were included. Standardized mean differences (SMDs) were calculated for pain and function at 2, 4, 8, and 12 weeks. Subgroup analyses for strong and weak/intermediate opioids were conducted. Meta-regression was performed to assess the impact of dosage (morphine equivalency) on pain relief. Risk ratios were calculated for safety at the final follow-up. Results: A total of 18 RCTs (9,283 participants) were included. Opioids demonstrated small benefits on pain at each time point, with SMDs ranging from –0.28 (95% confidence interval [95% CI] –0.38, –0.17) to –0.19 (95% CI –0.29, –0.08); similar effects were observed for function. Strong opioids demonstrated consistently inferior efficacy and overall worse safety than weak/intermediate opioids. Meta-regression revealed that incremental pain relief achieved beyond 20–50-mg doses was not substantial in the context of increased safety risks. Conclusion: Opioids provide minimal relief of OA symptoms within a 12-week period, and they are known to cause discomfort in a majority of patients. Clinicians and policy makers should reconsider the utility of opioids in the management of OA

Papilledema Secondary to Neurologic Lyme Borreliosis: A Meta-Case Series

Papilledema can be a manifestation of neurologic Lyme borreliosis (LB). The clinical manifestations and progression of these cases have not been comprehensively documented to date. We aimed to describe clinical and diagnostic features and to assess patient outcomes in cases of papilledema secondary to neurologic LB

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA): 2020 Guideline on Diagnosis and Management of Babesiosis

The purpose of this guideline is to provide evidence-based guidance for the most effective strategies for the diagnosis and management of babesiosis. The diagnosis and treatment of co-infection with babesiosis and Lyme disease will be addressed in a separate Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) guideline [1]. Recommendations for the diagnosis and treatment of human granulocytic anaplasmosis can be found in the recent rickettsial disease guideline developed by the Centers for Disease Control and Prevention [2]. The target audience for the babesiosis guideline includes primary care physicians and specialists caring for this condition, such as infectious diseases specialists, emergency physicians, intensivists, internists, pediatricians, hematologists, and transfusion medicine specialists