Angiotensin Receptor Blockers and Cognition: a Scoping Review.

PURPOSE OF REVIEW: To provide an overview of the association between angiotensin II receptor blocker (ARB) use and cognitive outcomes. RECENT FINDINGS: ARBs have previously shown greater neuroprotection compared to other anti-hypertensive classes. The benefits are primarily attributed to the ARB's effect on modulating the renin-angiotensin system via inhibiting the Ang II/AT1R pathway and activating the Ang II/AT2R, Ang IV/AT4R, and Ang-(1-7)/MasR pathways. These interactions are associated with pleiotropic neurocognitive benefits, including reduced ß-amyloid accumulation and abnormal hyperphosphorylation of tau, ameliorated brain hypo-fusion, reduced neuroinflammation and synaptic dysfunction, better neurotoxin clearing, and blood-brain barrier function restoration. While ACEis also inhibit AT1R, they simultaneously lower Ang II and block the Ang II/AT2R and Ang IV/AT4R pathways that counterbalance the potential benefits. ARBs may be considered an adjunctive approach for neuroprotection. This preliminary evidence, coupled with their underlying mechanistic pathways, emphasizes the need for future long-term randomized trials to yield more definitive results.

Considering Adverse Effects of Common Antihypertensive Medications in the ED.

PURPOSE OF REVIEW: To evaluate the adverse effects of common antihypertensive agents utilized or encountered in the Emergency Department. RECENT FINDINGS: All categories of antihypertensive agents may manifest adverse effects, inclusive of adverse drug reactions (ADRs), drug-to-drug interactions, or accidental overdose. Adverse effects, and specifically ADRs, may be stratified into the organ systems affected, might require specific time-sensitive interventions, could pose particular risks to vulnerable populations, and may result in significant morbidity, and potential mortality. Adverse effects of common antihypertensive agents may be encountered in the ED, necessitating that ED systems of care are poised to prevent, recognize, and intervene when adverse effects arise.

How Much Lowering of Blood Pressure Is Required to Prevent Cardiovascular Disease in Patients With and Without Previous Cardiovascular Disease?

PURPOSE OF REVIEW: To review the recent large-scale randomised evidence on pharmacologic reduction in blood pressure for the primary and secondary prevention of cardiovascular disease. RECENT FINDINGS: Based on findings of the meta-analysis of individual participant-level data from 48 randomised clinical trials and involving 344,716 participants with mean age of 65 years, the relative reduction in the risk of developing major cardiovascular events was proportional to the magnitude of achieved reduction in blood pressure. For each 5-mmHg reduction in systolic blood pressure, the risk of developing cardiovascular events fell by 10% (hazard ratio [HR] (95% confidence interval [CI], 0.90 [0.88 to 0.92]). When participants were stratified by their history of cardiovascular disease, the HRs (95% CI) in those with and without previous cardiovascular disease were 0.89 (0.86 to 0.92) and 0.91 (0.89 to 0.94), respectively, with no significant heterogeneity in these effects (adjusted P for interaction = 1.0). When these patient groups were further stratified by their baseline systolic blood pressure in increments of 10 mmHg from < 120 to ≥ 170 mmHg, there was no significant heterogeneity in the relative risk reduction across these categories in people with or without previous cardiovascular disease (adjusted P for interaction were 1.00 and 0.28, respectively). Pharmacologic lowering of blood pressure was effective in preventing major cardiovascular disease events both in people with or without previous cardiovascular disease, which was not modified by their baseline blood pressure level. Treatment effects were shown to be proportional to the intensity of blood pressure reduction, but even modest blood pressure reduction, on average, can lead to meaningful gains in the prevention of incident or recurrent cardiovascular disease.

Resistant hypertension and cardiovascular disease mortality in the US: results from the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Apparent treatment-resistant hypertension (aTRH) is a common condition associated with risk of cardiovascular events. However, the risk of cardiovascular mortality associated with aTRH in the US population is unknown. We aimed to assess the risk of cardiovascular disease (CVD) mortality associated with aTRH in the US population. METHODS: We analyzed data from 6357 adult hypertensive participants of the National Health and Nutrition Examination Survey (1988-1994 and 1999-2010) linked to the National Death Index. Based on presence of uncontrolled hypertension [blood pressure (BP) ≥140/90 mmHg] and the number of antihypertensives prescribed, we classified participants into the following groups: non-aTRH (BP < 140/90 mmHg and ≤ 3 antihypertensives); controlled aTRH (BP < 140/90 mmHg and ≥ 4 antihypertensives); and uncontrolled aTRH (BP ≥140/90 mmHg and ≥ 3 antihypertensives). RESULTS: Of the 6357 participants, 1522 had aTRH, representing a US prevalence of 7.6 million. Of the participants with aTRH, 432 had controlled aTRH and 1090 had uncontrolled aTRH. During follow-up (median 6 years), there were 550 CVD deaths. The cumulative incidence of CVD mortality was significantly higher in the aTRH group compared with non-aTRH group (log-rank p < 0.001). In fully adjusted models, aTRH was associated with a 47% higher risk of CVD mortality compared with the non-aTRH group [1.47 (1.1-1.96)]. Similar increase in risk of CVD mortality was noted across aTRH subgroups compared with the non-aTRH group: controlled aTRH [1.66 (1.03-2.68)] and uncontrolled aTRH [1.43 (1.05-1.94)]. Among non-aTRH subgroups, those on 3 antihypertensive medications had a 35% increased risk of CVD mortality than those on < 3 medications [1.35 (0.98-1.86)]. CONCLUSIONS: aTRH is a common condition, affecting approximately 7.6 million Americans. Regardless of BP control, people with aTRH remain at a higher risk of cardiovascular outcomes. The risk of cardiovascular disease mortality remains high among those with controlled BP on 3 medications (non-aTRH) or ≥ 4 medications (controlled aTRH), groups not generally considered at high risk. Future risk reduction interventions should consider focusing on these high-risk groups.

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure.

WHAT IS KNOWN AND OBJECTIVE: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist. METHODS: A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords:hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion. RESULTS AND DISCUSSION: All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors. WHAT IS NEW AND CONCLUSION: Based upon this review, individuals on antipsychotic agents, particularly clozapine, should be routinely monitored for hypertension, and addition of antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is indicated if hypertension occurs.

Type 2 diabetes-induced cardiovascular complications: comparative evaluation of spironolactone, atenolol, metoprolol, ramipril and perindopril.

The present study was carried out to study the effect of spironolactone, atenolol, metoprolol, ramipril and perindopril on cardiovascular complications in neonatal model of diabetes in rats, induced by administering 90 mg/kg streptozotocin (STZ), i.p. in 2-day-old rats. Our data suggest that spironolactone, metoprolol and perindopril prevent not only the STZ-induced metabolic abnormalities but also cardiovascular complications as evident from the reduction in cholesterol, triglyceride and decrease in cardiac hypertrophy which are the initial symptoms of congestive heart failure. Metoprolol and perindopril appears to be beneficial agents as compared to atenolol and ramipril.

Hypertension & dementia: Pathophysiology & potential utility of antihypertensives in reducing disease burden.

Dementia is a common cause of disability and dependency among the elderly due to its progressive neurodegenerative nature. As there is currently no curative therapy, it is of major importance to identify new ways to reduce its prevalence. Hypertension is recognised as a modifiable risk factor for dementia, particularly for the two most common subtypes; vascular dementia (VaD) and Alzheimer's disease (AD). From the current literature, identified through a comprehensive literature search of PubMed and Cochrane Library, this review aims to establish the stage in adulthood when hypertension becomes a risk for cognitive decline and dementia, and whether antihypertensive treatment is effective as a preventative therapy. Observational studies generally found hypertension in mid-life (age 45-64) to be correlated with an increased risk of cognitive decline and dementia incidence, including both VaD and AD. Hypertension manifesting in late life (age ≥ 65) was demonstrated to be less of a risk, to the extent that incidences of high blood pressure (BP) in the very elderly (age ≥ 75) may even be related to reduced incidence of dementias. Despite the evidence linking hypertension to dementia, there were conflicting findings as to whether the use of antihypertensives was beneficial for its prevention and this conflicting evidence and inconsistent results could be due to the methodological differences between the reviewed observational and randomised controlled trials. Furthermore, dihydropyridine calcium channel blockers and potassium-sparing diuretics were proposed to have neuroprotective properties in addition to BP lowering. Overall, if antihypertensives are confirmed to be beneficial by larger-scale homogenous trials with longer follow-up durations, treatment of hypertension, particularly in mid-life, could be an effective strategy to considerably lower the prevalence of dementia. Furthermore, greater clarification of the neuroprotective properties that some antihypertensives possess will allow for better clinical practice guidance on the choice of antihypertensive class for both BP lowering and dementia prevention.

Antihypertensive Effects of Sacubitril/Valsartan Versus Olmesartan: An Updated Systemic Review and Meta-Analysis of Randomized Controlled Trials.

Sacubitril/valsartan is a drug commonly prescribed for the management of hypertension. However, the complete understanding of its efficacy and safety as an antihypertensive agent remains a subject of ongoing investigation. To address this gap, a meta-analysis was conducted to assess and compare the efficacy and safety of sacubitril/valsartan in relation to olmesartan, an angiotensin receptor blocker (ARB). A thorough search of PubMed, Google Scholar, and Cochrane databases was performed to identify relevant randomized controlled trials (RCTs) and observational studies that could contribute to this meta-analysis. The selected studies were evaluated for their efficacy and safety parameters, including mean sitting and ambulatory blood pressure measurements, common side effects, adverse events, and drug discontinuation rates. A total of eight studies, involving 4488 hypertensive patients, were included in this analysis. Among the participants, 63.5% were administered sacubitril/valsartan, while 36.5% received olmesartan. The analysis revealed significant changes in mean sitting systolic blood pressure (MsSBP), mean sitting diastolic blood pressure (MsDBP), and mean sitting pulse pressure (MsPP) favoring sacubitril/valsartan, with p-values <0.00001, 0.07, and <0.00001, respectively. Additionally, sacubitril/valsartan demonstrated a significant reduction in mean ambulatory systolic blood pressure (MaSBP), mean ambulatory diastolic blood pressure (MaDBP), and mean ambulatory pulse pressure (MaPP) with p-values of 0.001, 0.001, and 0.02, respectively. However, it is important to note that safety outcomes indicated that sacubitril/valsartan was associated with slightly less favorable results compared to olmesartan. This meta-analysis highlights that sacubitril/valsartan exhibits superior efficacy in reducing blood pressure parameters compared to olmesartan in hypertensive patients. Nevertheless, its safety profile appears to be slightly less favorable. To reinforce these findings and provide more robust evidence, further studies with larger sample sizes should be conducted in the future. This comprehensive review serves as a valuable resource for healthcare professionals and researchers seeking to make informed decisions regarding antihypertensive treatment options.

Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp.

Despite the advancement in drug discovery for cancer therapy, drug repurposing remains an exceptional opportunistic strategy. This approach offers many advantages (faster, safer, and cheaper drugs) typically needed to overcome increased challenges, i.e., side effects, resistance, and costs associated with cancer therapy. However, not all drug classes suit a patient's condition or long-time use. For that, repurposing chronically used medications is more appealing. This review highlights the importance of repurposing anti-diabetic and anti-hypertensive drugs in the global fight against human malignancies. Extensive searches of all available evidence (up to 30 March 2023) on the anti-cancer activities of anti-diabetic and anti-hypertensive agents are obtained from multiple resources (PubMed, Google Scholar, ClinicalTrials.gov, Drug Bank database, ReDo database, and the National Institutes of Health). Interestingly, more than 92 clinical trials are evaluating the anti-cancer activity of 14 anti-diabetic and anti-hypertensive drugs against more than 15 cancer types. Moreover, some of these agents have reached Phase IV evaluations, suggesting promising official release as anti-cancer medications. This comprehensive review provides current updates on different anti-diabetic and anti-hypertensive classes possessing anti-cancer activities with the available evidence about their mechanism(s) and stage of development and evaluation. Hence, it serves researchers and clinicians interested in anti-cancer drug discovery and cancer management.

Novel Approaches in Chronic Renal Failure without Renal Replacement Therapy: A Review.

Chronic kidney disease (CKD) is characterized by renal parenchymal damage leading to a reduction in the glomerular filtration rate. The inflammatory response plays a pivotal role in the tissue damage contributing to renal failure. Current therapeutic options encompass dietary control, mineral salt regulation, and management of blood pressure, blood glucose, and fatty acid levels. However, they do not effectively halt the progression of renal damage. This review critically examines novel therapeutic avenues aimed at ameliorating inflammation, mitigating extracellular matrix accumulation, and fostering renal tissue regeneration in the context of CKD. Understanding the mechanisms sustaining a proinflammatory and profibrotic state may offer the potential for targeted pharmacological interventions. This, in turn, could pave the way for combination therapies capable of reversing renal damage in CKD. The non-replacement phase of CKD currently faces a dearth of efficacious therapeutic options. Future directions encompass exploring vaptans as diuretics to inhibit water absorption, investigating antifibrotic agents, antioxidants, and exploring regenerative treatment modalities, such as stem cell therapy and novel probiotics. Moreover, this review identifies pharmaceutical agents capable of mitigating renal parenchymal damage attributed to CKD, targeting molecular-level signaling pathways (TGF-ß, Smad, and Nrf2) that predominate in the inflammatory processes of renal fibrogenic cells.

Assessing the Effect of the Anti-tuberculosis Drug Rifampicin on Known Hypertensive Patients With Tuberculosis in a Tertiary Care Center.

Background Epidemiological evidence suggests an indirect link between hypertension and tuberculosis, and several studies have reported that rifampicin has potentially diminished the hypotensive effects of many anti-hypertensive agents by inducing cytochrome P450. This study investigates rifampicin's effect on the target blood pressure in known hypertensive patients whose blood pressure had been previously controlled with anti-hypertensive drugs. Methodology This prospective observational study was conducted at the Institute of Internal Medicine, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, from June 2021 to December 2022. A total of 160 patients with known hypertension on anti-hypertensive drugs were recruited for this study. All these patients had been recently diagnosed with tuberculosis and had been treated with rifampicin-based anti-tuberculosis therapy (ATT). Results The maximum number of patients were under 50 years of age and predominantly male (67%). A total of 91 (57%) patients were hypertensive for less than five years, and the remaining patients were hypertensive within 6-10 years or more than 10 years. However, these patients had other comorbidities such as diabetes mellitus (32%) and coronary artery disease (27%). Before ATT, the mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) was recorded to be 130/80 mmHg. The last six months' course of ATT showed mean values around 154/96 mmHg even after adding additional/multiple anti-hypertensive drugs. After discontinuation of ATT, the mean SBP/DBP was effectively 130/80 mmHg at four weeks. Conclusions Rifampicin significantly diminishes the hypotensive effects of many well-established anti-hypertensives such as calcium channel blockers, beta-blockers, and diuretics to maintain blood pressure.

Anti-hypertensive use for non-severe gestational hypertension in Botswana: A case-control study.

OBJECTIVE: The fetal risks and benefits of antihypertensives to treat gestational hypertension in pregnancy are understudied, particularly in low- and middle-income countries. METHODS: We performed a nested case-control study within a retrospective cohort of obstetrical patients in Botswana from 2014 to 2019. We included women carrying singletons who developed new onset non-severe hypertension (140-159 mm Hg systolic or 90-109 mm Hg diastolic blood pressure) after 20 weeks of pregnancy. Cases were defined as women with either small-for-gestational-age (SGA) infants or stillbirth, analyzed separately; controls were otherwise similar women without the adverse outcome in each analysis. RESULTS: We identified 1932 cases of SGA (7925 controls) and 316 cases of stillbirth (9619 controls). Cases with SGA were more likely to have used an anti-hypertensive than controls (33% vs 29%, adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.15-1.43). Cases with stillbirth were more likely to have used an anti-hypertensive than controls (42% versus 29%, aOR 1.45, 95% CI 1.14-1.83). CONCLUSION: Anti-hypertensive use for new-onset gestational hypertension was associated with an increased risk of having an SGA infant or a stillbirth among women who never developed severe hypertension. These data support conduct of a randomized clinical trial to determine the appropriate use of anti-hypertensives in non-severe gestational hypertension.

Adherence to anti-hypertensive medication in pregnancy.

OBJECTIVES: To assess adherence to anti-hypertensive medication by pregnant women and to identify the factors associated with adherence or lack thereof. STUDY DESIGN: Observational study in 100 pregnant women with either chronic hypertension or gestational hypertension who were being treated with at least one anti-hypertensive medication and attending antenatal clinics at one of two maternity hospitals. In-depth interviews were conducted with a subset of 27 women from the same group. Quotes from interview transcripts were used to illustrate the quantitative results. MAIN OUTCOME MEASURES: BP control, self-reported adherence, complexity of medication regimen. RESULTS: Participants (mean age 33 [±4.9] years; mean gestation 29 (±7) weeks) had a median blood pressure (BP) of 130/80 mmHg (IQR: 16/15). Sixty-five women had chronic hypertension, of whom 13 were diagnosed during pregnancy, before 20 weeks gestation. Thirty-five women had gestational hypertension. Ninety-two per cent of participants had sub-optimal adherence. There were no significant differences in adherence scores between participants with chronic hypertension and their counterparts. The main contributors to sub-optimal adherence were intentionally putting up with medical problems before taking any action, confusion about the medication, and making changes to the recommended medication regimen to suit lifestyle. CONCLUSIONS: Nine out of ten pregnant women using anti-hypertensives self-reported some degree of suboptimal adherence, intentionally and/or unintentionally. Health professionals, including pharmacists, general practitioners and obstetricians, have a role in promoting optimal medication adherence.

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors.

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

Electroanalysis Applied to Compatibility and Stability Assays of Drugs: Carvedilol Study Case.

Carvedilol (CRV) is a non-selective blocker of α and ß adrenergic receptors, which has been extensively used for the treatment of hypertension and congestive heart failure. Owing to its poor biopharmaceutical properties, CRV has been incorporated into different types of drug delivery systems and this necessitates the importance of investigating their compatibility and stability. In this sense, we have investigated the applicability of several electroanalytical tools to assess CRV compatibility with lipid excipients. Voltammetric and electrochemical impedance spectroscopy techniques were used to evaluate the redox behavior of CRV and lipid excipients. Results showed that Plurol® isostearic, liquid excipient, and stearic acid presented the greatest anode peak potential variation, and these were considered suitable excipients for CRV formulation. CRV showed the highest stability at room temperature and at 50 °C when mixed with stearic acid (7% w/w). The results also provided evidence that electrochemical methods might be feasible to complement standard stability/compatibility studies related to redox reactions.

Economic evaluation of olmesartan/amlodipine fixed-dose combination for hypertension treatment in China.

Objectives: To evaluate the cost-effectiveness of olmesartan/amlodipine fixed-dose combination vs olmesartan and amlodipine free combination, amlodipine single drug, and valsartan/amlodipine fixed-dose combination in the treatment of hypertensive patients from payer perspective in China.Methods: A Markov model was constructed, which included five health states of hypertensive patients who are aged 35-84 years at baseline and free of cardiovascular disease. Clinical data were obtained from a network meta-analysis. Epidemiology data, adverse events (AEs), cost, and utility data were obtained from the literature. The cost associated with AEs was estimated based on the cost of same symptoms of hypertensive patients in an electric medical record database. The model projected quality-adjusted life years (QALYs) gained, total costs per patient in a 20-year time horizon, and incremental cost-effectiveness ratios. Probability sensitivity analyses (PSA) and one-way sensitivity analyses were conducted for the main parameters to test the robustness of the model.Results: Compared to olmesartan and amlodipine free combination, amlodipine, and valsartan/amlodipine fixed-dose combination, treatment with olmesartan/amlodipine fixed-dose combination led to fewer CVD events and deaths; resulted in an incremental cost of ¥-5,439 ($-791.36), ¥6,530 ($950.09), and ¥-1,019 ($-148.26) and gained additional QALYs of 0.052, 0.094, and 0.037 per patient, respectively. Compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, olmesartan/amlodipine fixed-dose combination was dominant. Compared with amlodipine alone, the incremental cost-effectiveness ratios were below the WHO recommended cost-effectiveness threshold, indicating the olmesartan/amlodipine fixed-dose combination was a cost-effective option for hypertensive patients in China. The 10-years' time horizon scenario analysis showed similar results to the 20-years' time horizon. Probabilistic sensitivity analysis and one-way sensitivity analyses showed the robustness of the model results.Conclusions: Olmesartan/amlodipine fixed-dose combination confers better health outcomes and costs less compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, and is cost-effective compared to amlodipine for hypertension treatment in China.

Effect of X-Ray Irradiation on Some Analgesics, Anti-Diabetics, PPI'S, Anti-Hypertensives, Heart Failure Drugs in Tablet and Capsule Forms.

X-ray is an ionizing-radiation and it has been used in many processes due to the developing technology. For security purposes, X-ray instruments are been using at the entrance of the airports, shopping centers, etc. In this study, potential effects of X-ray were investigated on five different types of drugs: analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), proton pump inhibitors (lansoprazole, pantoprazole sodium sesquihydrate), anti-diabetics (metformin HCl, pioglitazone), heart failure drugs (verapamil HCl, spironolactone) and anti-hypertensives (losartan, clopidogrel hydrogen sulphate) by several different methods. In our previous study these drugs were analyzed by ESR before and after X-ray irradiation (0,24; 1,2; 58 mGy). According to the ESR results, acetylsalicylic acid tablets were affected after 58 mGy irradiation due to coated polymer (HPMC). In conclusion, these drugs were investigated before and after 0,24; 1,2 and 58 mGy X-ray irradiation by UV-spectrophotometry, dissolution test, SEM, FT-IR, DSC/TGA in this article. As a result of this study, X-ray did not cause a significant effect on drugs generally. Only a few significant differences were detected by different studies (for metformin HCl by DSC/TGA, for acetylsalicylic acid by dissolution test, and for acetaminophen and acetylsalicylic acid by UV spectrophotometry were detected significantly difference before and after irradiation).

Do ß-adrenoreceptor blocking drugs associate with reduced risk of symptomatic osteoarthritis and total joint replacement in the general population? A primary care-based, prospective cohort study using the Clinical Practice Research Datalink.

INTRODUCTION: To investigate if ß-adrenoreceptor blocking drug (ß-blocker) prescription reduces the risk of knee or hip osteoarthritis, total joint replacement and analgesic prescription. SETTING: Primary care. METHODS AND ANALYSIS: This is a cohort study using data from the Clinical Practice Research Datalink. Two separate analyses will be performed. Study 1 will be on the association between ß-blocker prescription and incident knee/hip osteoarthritis. Inclusion criteria will be age ≥40 years. Exposed participants will be those with ≥2 continuous ß-blocker prescriptions, and the index date will be the date of the first prescription of ß-blocker. Unexposed participants will include up to four controls matched for age, sex, general practice surgery and propensity score for ß-blocker prescription. Exclusion criteria will include contraindications to ß-blockers, consultations for osteoarthritis or potent analgesic prescription before the index date. Outcomes will be knee osteoarthritis (primary outcome), hip osteoarthritis, knee pain and hip pain. Study 2 will be on the association between ß-blocker prescription and total joint replacement and analgesic prescription in people with osteoarthritis. Inclusion criteria will be age ≥40 years, knee or hip osteoarthritis, and index date will be as in study 1. Unexposed participants will be as in study 1, additionally matched for consultation for knee or hip osteoarthritis prior to the index date. Exclusion criteria will include contraindications to ß-blockers and osteoarthritis in other joints prior to the index date. Outcomes will be total knee replacement (primary outcome), total hip replacement and new analgesic prescription. STATISTICAL ANALYSIS: Kaplan-Meier curves will be plotted, and Cox proportional HRs and 95% CIs will be calculated. Stratified analysis will be performed by class of ß-blocker, intrinsic sympathomimetic effect and indication(s) for prescription. ETHICS AND DISSEMINATION: This study was ethically approved by the Independent Scientific Advisory Committee of the Medicines and Healthcare Authority (Ref 18_227R). The results of this study will be published in peer-reviewed journals and presented at conferences. SUMMARY: This prospective cohort study will evaluate the analgesic potential of commonly used drugs for osteoarthritis pain.

Adapting a club-based medication delivery strategy to a hypertension context: the CLUBMEDS Study in Nigeria.

INTRODUCTION: The prevalence of hypertension in sub-Saharan Africa is among the world's highest; however, awareness, treatment and control of hypertension in this region are suboptimal. Among other barriers, the overburdened healthcare system poses a great challenge for hypertension control. Community peer-support groups are an alternative and promising strategy to improve adherence and blood pressure (BP) control. The CLUBMEDS study aims to evaluate the feasibility and impact of adherence clubs to improve hypertension control in Nigeria. METHODS AND ANALYSIS: The CLUBMEDS study will include a formative (pre-implementation) qualitative evaluation, a pilot study and a process (postimplementation) qualitative evaluation. At the formative stages, focus group discussions with patient groups and in-depth interviews with healthcare providers, managers and key decision makers will be conducted to understand the feasibility, barriers and facilitators, opportunities and challenges for the successful implementation of the CLUBMEDS strategy. The CLUBMEDS pilot study will be implemented in two primary healthcare facilities, one urban and one rural, in Southeast Nigeria. Each adherence club, which consists of a group of 10-15 patients with hypertension under the leadership of a role-model patient, serves as a support group to encourage and facilitate adherence, BP self-monitoring and medication delivery on a monthly basis. A process evaluation will be conducted at the end of the pilot study to evaluate the acceptability and engagement with the CLUBMEDS strategy. To date, 104 patients were recruited and grouped into nine clubs, in which patients will be followed-up for 6 months. ETHICS AND DISSEMINATION: The study was approved by the University of Abuja Teaching Hospital and the Federal Teaching Hospital Abakaliki Human Research Ethics Committees and all patients provided informed consent. Our findings will provide preliminary data on the potential effectiveness and acceptance of this strategy in a hypertension context. Study findings will be disseminated via scientific forums.

Health-Promoting Components in Fermented Foods: An Up-to-Date Systematic Review.

Fermented foods have long been produced according to knowledge passed down from generation to generation and with no understanding of the potential role of the microorganism(s) involved in the process. However, the scientific and technological revolution in Western countries made fermentation turn from a household to a controlled process suitable for industrial scale production systems intended for the mass marketplace. The aim of this paper is to provide an up-to-date review of the latest studies which investigated the health-promoting components forming upon fermentation of the main food matrices, in order to contribute to understanding their important role in healthy diets and relevance in national dietary recommendations worldwide. Formation of antioxidant, bioactive, anti-hypertensive, anti-diabetic, and FODMAP-reducing components in fermented foods are mainly presented and discussed. Fermentation was found to increase antioxidant activity of milks, cereals, fruit and vegetables, meat and fish. Anti-hypertensive peptides are detected in fermented milk and cereals. Changes in vitamin content are mainly observed in fermented milk and fruits. Fermented milk and fruit juice were found to have probiotic activity. Other effects such as anti-diabetic properties, FODMAP reduction, and changes in fatty acid profile are peculiar of specific food categories.