Project description:: Although antihypertensive medication is usually continued indefinitely, observations during wash-out phases in hypertension trials have shown that withdrawal of antihypertensive medication might be well tolerated to do in a considerable proportion of people. A systematic review was completed to determine the proportion of people remaining normotensive for 6 months or longer after cessation of antihypertensive therapy and to investigate the safety of withdrawal. The mean proportion adjusted for sample size of people remaining below each study's threshold for hypertension treatment was 0.38 at 6 months [95% confidence interval (CI) 0.37-0.49; 912 participants], 0.40 at 1 year (95% CI 0.40-0.40; 2640 participants) and 0.26 at 2 years or longer (95% CI 0.26-0.27; 1262 participants). Monotherapy, lower blood pressure before withdrawal and body weight were reported as predictors for successful withdrawal. Adverse events were more common in those who withdrew but were minor and included headache, joint pain, palpitations, oedema and a general feeling of being unwell. Prescribers should consider offering patients with well controlled hypertension a trial of withdrawal of antihypertensive treatment with subsequent regular blood pressure monitoring.
Project description:OBJECTIVES:To explore general practitioners' (GPs) routines and considerations on (de)prescribing antihypertensive medication (AHM) in older patients, their judgement on usability of the current guideline and needs for future support. DESIGN:Semistructured interviews. SETTING:Dutch general practice. PARTICIPANTS:Fifteen GPs were purposively sampled based on level of experience and practice characteristics until saturation was reached. RESULTS:GPs appeared reluctant to start AHM, especially in patient >80 years. High systolic blood pressure and history of cardiovascular disease or diabetes were enablers to start or intensify treatment. Reasons to refrain from this were frailty and patient preference. GPs described a tendency to continue AHM regimens unchanged, influenced by daily time constraints, automated prescription routines and anticipating discomfort when disturbing patients' delicate balance. GPs were only inclined to deprescribe AHM in terminally ill patients or after prolonged achievement of target levels in combination with side effects or patient preference. Deprescription was facilitated when GPs had experience with patients showing increased quality of life after deprescription and was withheld by anticipated regret (ie, GPs' fear of a stroke after deprescribing). GPs felt insufficient guidance from current guidelines, especially on deprescription. CONCLUSIONS:GPs are reluctant to start or deprescribe AHM in older people and have a propensity to continue AHM within a daily routine that insufficiently supports critical medication review. (De)prescription is influenced by patient preferences and anticipated regret and current guidelines provide insufficient guidance.
Project description:To address the epidemic of hypertension in blacks born and living in sub-Saharan Africa, we compared in a randomised clinical trial (NCT01030458) single-pill combinations of old and new antihypertensive drugs in patients (30-69 years) with uncomplicated hypertension (140-179/90-109?mm?Hg). After ?4 weeks off treatment, 183 of 294 screened patients were assigned to once daily bisoprolol/hydrochlorothiazide 5/6.25?mg (n=89; R) or amlodipine/valsartan 5/160?mg (n=94; E) and followed up for 6 months. To control blood pressure (<140/<90?mm?Hg), bisoprolol and amlodipine could be doubled (10?mg per day) and ?-methyldopa (0.5-2?g per day) added. Sitting blood pressure fell by 19.5/12.0?mm?Hg in R patients and by 24.8/13.2?mm?Hg in E patients and heart rate decreased by 9.7 beats per minute in R patients with no change in E patients (-0.2 beats per minute). The between-group differences (R minus E) were 5.2?mm?Hg (P<0.0001) systolic, 1.3?mm?Hg (P=0.12) diastolic, and 9.6 beats per minute (P<0.0001). In 57 R and 67 E patients with data available at all visits, these estimates were 5.5?mm?Hg (P<0.0001) systolic, 1.8?mm?Hg (P=0.07) diastolic and 9.8 beats per minute (P<0.0001). In R compared with E patients, 45 vs 37% (P=0.13) proceeded to the higher dose of randomised treatment and 33 vs 9% (P<0.0001) had ?-methyldopa added. There were no between-group differences in symptoms except for ankle oedema in E patients (P=0.012). In conclusion, new compared with old drugs lowered systolic blood pressure more and therefore controlled hypertension better in native African black patients.
Project description:ObjectivesNeuropsychiatric symptoms (NPS) are very common in older patients with dementia. There is increasing evidence that hypoperfusion of the brain plays a role in the development of NPS. The aim of this study is to assess whether there is an association between low systolic blood pressure (SBP) and NPS and if NPS are more prevalent in older people with dementia using antihypertensive medication.MethodsWe studied the baseline data from participants in the Communication, Systematic pain treatment, Medication review, Organized activities and Safety study, a multicenter clustered trial with 765 participants from 72 nursing home units from 37 nursing homes in Norway. SBP (lowest quartile vs rest) and use of antihypertensive medication were predictors and Neuropsychiatric Inventory-Nursing Home version (NPI-NH) score (total and clusters) was the outcome. Missing data were imputed, except for missing data in predictors. We used a mixed model analysis adjusted for age, sex and Minimal Mental State Examination (MMSE) score. In a sensitivity analysis, continuous SBP values were used.ResultsIn total, 412 patients were included with a mean age of 86.9 years, 53.9% had a MMSE score of <11. There was no difference in total NPI-NH score between low and high SBP (difference -1.07, Pdj = 0.62). There was no difference between high and low SBP and the NPI clusters. The use of antihypertensive medication was not associated with a different total or cluster NPI-NH score compared to no use (difference -0.99, Padj = 0.95, Pall = 0.37-0.99, respectively). In the sensitivity analyses with the continuous SBP levels, there was no association between SBP and NPI-NH score (estimate 1.00, 95%CI 0.98-1.01, P = 0.25).ConclusionWe found no association between low SBP and NPS, nor between antihypertensive use and NPS.
Project description:We analyze a network of needle-sharing ties among 117 people who inject drugs (PWID) in rural Puerto Rico, using exponential random graph modeling to examine whether network members engage in partner restriction to lower their risk of contracting HIV or hepatitis C (HCV), or in informed altruism to prevent others from contracting these infections. Although sharing of used syringes is a significant risk factor for transmission of these diseases among PWID, we find limited evidence for partner restriction or informed altruism in the network of reported needle-sharing ties. We find however that sharing of needles is strongly reciprocal, and individuals with higher injection frequency are more likely to have injected with a used needle. Drawing on our ethnographic work, we discuss how the network structures we observe may relate to a decision-making rationale focused on avoiding withdrawal sickness, which leads to risk-taking behaviors in this poor, rural context where economic considerations often lead PWID to cooperate in the acquisition and use of drugs.
Project description:BackgroundThe short-term safety of and blood pressure changes after withdrawing hypertension treatment in older adults in preparation for clinical trials have not been well established.MethodsParticipants were enrolled in a clinical trial and antihypertensive medications were tapered over 3 weeks (week 1: reduction by 25%-50%; week 2: 50%-75%, week 3: off). Blood pressure was measured at the initial visit and after stopping all antihypertensive therapy (personnel) and twice a day during the taper phase (provided monitor). Trend analyses and linear models were used to assess changes in blood pressure.ResultsAll participants (n = 53, mean age = 71 years, total of 1158 readings) successfully tapered their medications with no symptoms. Only 2% of the readings exceeded 180/100 mm Hg, but none were consecutive. Blood pressure gradually increased with an overall increase of 12/6 mm Hg, 95% confidence interval (4/1, 21/11). The daily increase in blood pressure was 0.2 mm Hg (standard error = 0.1) in both the systolic and diastolic blood pressure. Increases in systolic and diastolic blood pressure were comparable for all antihypertensive classes (P > .05 for all).ConclusionShort-term (<3-4 weeks) withdrawal of antihypertensive therapy in older adults with hypertension is safe and is associated with mild increases in blood pressure.
Project description:Given the gut microbiota involve aging processing, we performed comparative analysis of gut bacteriophage between older and young subjects using next-generation sequencing (NGS). In our previous study, we found that the Ruminococcaceae is higher in aged subjects comparing to young one. To identify the bacteriophage targeting to the Ruminococcaceae, we also access the composition of phage in the Ruminococcaceae (ATCC, TSD-27) after incubated with human stool samples. The Lactobacillus (ATCC, LGG) targeting phage was used as the control. The virome sequencing analysis using NGS indicated that Myoviridae are high enrich in young subjects and predominate in TSD-27 targeting phage.
Project description:Hypertension continues to be an important public health concern because of its associated morbidity, mortality and economic impact on the society. It is a significant risk factor for cardiovascular, cerebrovascular and renal complications. It has been estimated that by 2025, 1.56 billion individuals will have hypertension. The increasing prevalence of hypertension and the continually increasing expense of its treatment influence the prescribing patterns among physicians and compliance to the treatment by the patients. A number of national and international guidelines for the management of hypertension have been published. Since many years ago, diuretics were considered as the first-line drugs for treatment of hypertension therapy; however, the recent guidelines by the Joint National Commission (JNC8 guidelines) recommend both calcium channel blockers as well as angiotensin-converting enzyme inhibitors as first-line drugs, in addition to diuretics. Antihypertensive drug combinations are generally used for effective long-term management and to treat comorbid conditions. This review focuses on the antihypertensive medication utilization, their cost factors, adherence to treatment by patients, and physicians' adherence to guidelines in prescribing medications in different settings including Indian scenario. The antihypertensive medication prescribing pattern studies help in monitoring, evaluation and necessary modifications to the prescribing habits to achieve rational and cost-effective treatment. Additionally, periodic updating of recommended guidelines and innovative drug formulations, and prescription monitoring studies help in rational use of antihypertensive drugs, which can be tailored to suit the patients' requirements, including those in the developing countries.
Project description:OBJECTIVES:To assess the incremental effects of adding extra antihypertensive drugs from a new class to a patient's regimen. DESIGN:Instrumental variable analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). To account for confounding by indication-when treatments seem less effective if they are administered to sicker patients-randomization status was used as the instrumental variable. Patients' randomization status was either intensive (systolic blood pressure target <120 mm Hg) or standard (systolic blood pressure target <140 mm Hg) treatment. Results from instrumental variable models were compared with those from standard multivariable models. SETTING:Secondary data analysis of a randomized clinical trial conducted at 102 sites in 2010-15. PARTICIPANTS:9092 SPRINT participants with hypertension and increased cardiovascular risk but no history of diabetes or stroke. MAIN OUTCOMES MEASURES:Systolic blood pressure, major cardiovascular events, and serious adverse events. RESULTS:In standard multivariable models not adjusted for confounding by indication, addition of an antihypertensive drug from a new class was associated with modestly lower systolic blood pressure (-1.3 mm Hg, 95% confidence interval -1.6 to -1.0) and no change in major cardiovascular events (absolute risk of events per 1000 patient years, 0.5, 95% confidence interval -1.5 to 2.3). In instrumental variable models, the addition of an antihypertensive drug from a new class led to clinically important reductions in systolic blood pressure (-14.4 mm Hg, -15.6 to -13.3) and fewer major cardiovascular events (absolute risk -6.2, -10.9 to -1.3). Incremental reductions in systolic blood pressure remained large and similar in magnitude for patients already taking drugs from zero, one, two, or three or more drug classes. This finding was consistent across all subgroups of patients. The addition of another antihypertensive drug class was not associated with adverse events in either standard or instrumental variable models. CONCLUSIONS:After adjustment for confounding by indication, the addition of a new antihypertensive drug class led to large reductions in systolic blood pressure and major cardiovascular events among patients at high risk for cardiovascular events but without diabetes. Effects on systolic blood pressure persisted across all levels of baseline drug use and all subgroups of patients.
Project description:Herbicide resistance is a worldwide problem in weed control. This prompts researchers to look for new modes of action to slow down the evolution of herbicide-resistant weeds. This research aims to determine the herbicidal action of thiazolo[3,2-a]pyrimidines derivatives, which are well known as antihypertensive drugs. The phytotoxic effects of ten compounds were investigated using leaf disc discoloration test and seed germination bioassay. At concentrations of 125 to 250 mg/L, the 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (c) was highly active against Oldenlandia verticillata and Eleusine indica. At application rates of 1.25 to 2.5 kg ai/ha, formulated c demonstrated selective post-emergence and pre-emergence herbicidal activity against O. verticillata, E. indica and Cyperus iria. In the crop tolerance test, formulated c outperformed the commercial herbicide diuron, with aerobic Oryza sativa being the most tolerant, followed by Zea mays, and Brassica rapa. The addition of calcium chloride partially nullified compound c's inhibitory effects on weed shoot growth, indicating that it has potential as a calcium channel blocker. Compound c acted by triggering electrolyte leakage without affecting photosystem II. These findings imply that c could be explored further as a template for developing new herbicides with novel modes of action.