British journal of clinical pharmacology最新文献

{"title":"Core medication use in general practice prescriptions: A pilot study evaluating the Drug Utilization 90% Index in Irish general practice.","authors":"Caroline McCarthy, Patrick Moynagh, Tom Fahey, Fiona Boland, Frank Moriarty","doi":"10.1111/bcp.16356","DOIUrl":"https://doi.org/10.1111/bcp.16356","url":null,"abstract":"<p><strong>Aims: </strong>The Drug Utilization 90% Index (DU90%), the number of medicines making up 90% of a doctor's prescribing, is a simple tool that can be used to describe core prescribing patterns. This research aimed to pilot the application of the DU90% in the Irish context, to investigate the relationship between the DU90% and prescriber and practice characteristics and prescribing quality.</p><p><strong>Methods: </strong>Retrospective observational study using anonymous prescription data from a sample of Irish general practitioners (GPs). Participating GPs provided demographic details and extracted prescription data for 2018-2022 using their existing software systems. The DU90% was calculated annually at both the practice and prescriber level. Prescribing quality indicators included antibiotic, benzodiazepine prescribing rates and high-risk nonsteroidal anti-inflammatory drug prescribing. The association of the DU90% with prescriber and practice characteristics and prescribing quality indicators was explored with multilevel modelling.</p><p><strong>Results: </strong>Thirty-eight prescribers from 22 different practices were included. The mean DU90% for prescribers was 141.5 (standard deviation 12.9) and for practices was 145.62 (standard deviation 11.87). Practices in receipt of the rural deprivation grant had a significantly lower DU90% (incidence rate ratio 0.94, 95% confidence interval 0.88-0.98). There was no evidence of an association between prescriber-level characteristics and the DU90% (sex, years qualified, number of sessions worked). There was a small positive relationship between the prescriber DU90% and total prescriptions, antibiotic and benzodiazepine prescribing rates, and higher rates of high-risk nonsteroidal anti-inflammatory drug prescriptions.</p><p><strong>Conclusion: </strong>Applying the DU90% to Irish general practice prescriptions is feasible, revealing that GPs typically use 140 medicines in the bulk of their prescribing.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review and meta-analysis of vancomycin therapeutic level for treatment of vancomycin-sensitive enterococcal infections.","authors":"Wasan Katip, Shaun Wen Huey Lee, Nongyao Kasatpibal, Ajaree Rayanakorn","doi":"10.1111/bcp.16362","DOIUrl":"https://doi.org/10.1111/bcp.16362","url":null,"abstract":"<p><strong>Aims: </strong>Evidence on the optimal targets of vancomycin for treating other Gram-positive infections apart from methicillin-resistant Staphylococcus aureus (MRSA) is lacking. This review aims to identify the recommended vancomycin therapeutic level for favourable clinical outcomes among patients infected with vancomycin-sensitive enterococcal infections.</p><p><strong>Methods: </strong>Analytical studies describing the vancomycin levels of vancomycin-sensitive enterococcal infections among adult population were searched. The primary outcome was 30-day all-cause mortality, and the secondary outcomes were clinical failure and nephrotoxicity. Study characteristics were extracted and pooled using random-effects meta-analysis. The study quality was assessed using the Joanna Briggs Institute critical appraisal tool.</p><p><strong>Results: </strong>A total of nine retrospective cohorts studies involving 1013 patients with vancomycin-sensitive enterococci were included. The meta-analysis found that high area under the curve to minimum inhibitory concentration ratio (AUC/MIC) of vancomycin ≥ 389 mg*h/L significantly lowered the 30-day mortality (odds ratio [OR], 0.44, 95% confidence interval [CI], 0.26-0.75). Analysis of the target AUC/MIC showed that high vancomycin AUC/MIC (≥ 389-400 mg*h/L) significantly reduced clinical failure rate (OR 0.59, 95% CI 0.37-0.94). The mortality and treatment failure rates did not differ significantly between those with high or low trough levels. Higher vancomycin AUC/MIC and trough levels were significantly associated with increased nephrotoxicity (OR 3.11, 95% CI 1.65-5.89; OR 2.95, 95% CI 1.60-5.44, respectively).</p><p><strong>Conclusions: </strong>The use of a higher vancomycin AUC/MIC concentration can be effective to reduce 30-day mortality and clinical failure but this needs to take into consideration the risk of nephrotoxicity. Well-conducted prospective studies are warranted due to the scarcity of evidence.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-prescription of low-dose methotrexate and trimethoprim-sulfamethoxazole and the 30-day risk of death among older adults: A cohort study.","authors":"Hasti Sadeghi, Fatemeh Ahmadi, Eric McArthur, Jessica M Sontrop, Sheikh S Abdullah, Brad L Urquhart, Richard B Kim, Flory T Muanda","doi":"10.1111/bcp.16365","DOIUrl":"https://doi.org/10.1111/bcp.16365","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study was to characterize the risk of death in older adults co-prescribed low-dose methotrexate and TMP-SMX vs. low-dose methotrexate and a cephalosporin.</p><p><strong>Methods: </strong>We conducted a retrospective, population-based, new-user cohort study in Ontario, Canada (April 1, 2002-August 1, 2022) using linked administrative healthcare data. Older adults taking low-dose methotrexate who were newly co-prescribed TMP-SMX (n = 1602) were matched 1:1 with those who were newly co-prescribed a cephalosporin. The primary outcome was death within 30 days of the antibiotic dispensing date. Secondary outcomes included all-cause hospitalization, a hospital visit with myelosuppression and a hospitalization with persistent infection defined as the main diagnosis. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RR) were obtained using modified Poisson regression.</p><p><strong>Results: </strong>In a propensity-score matched cohort of 3204 adults taking low-dose methotrexate, the 30-day risk of death was similar in adults co-prescribed TMP-SMX vs. a cephalosporin (14/1602 [0.87%] vs. 15/1602 [0.94%]; RR 0.93 [95% CI 0.45-1.93]). The risk of all-cause hospitalization (RR 1.49 [95% CI 1.13-1.97]) and infection (RR 2.78 [95% CI 1.30-5.95]) was higher in adults treated with TMP-SMX than those treated with cephalosporins.</p><p><strong>Conclusions: </strong>In older adults taking low-dose methotrexate, co-prescription of TMP-SMX vs. a cephalosporin was not associated with a higher 30-day risk of death but was associated with a higher 30-day risk of all-cause hospitalization and hospital admission with persistent infection. If verified, these risks should be balanced against the benefits of co-prescribing TMP-SMX and low-dose methotrexate.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized parathyroid hormone therapy for hypoparathyroidism: Insights from pharmacokinetic-pharmacodynamic modelling.","authors":"Maira Visscher, Manon Schuls-Fouchier, Annika M A Berends, Anneke C Muller Kobold, Nieko C Punt, Daan J Touw","doi":"10.1111/bcp.16342","DOIUrl":"https://doi.org/10.1111/bcp.16342","url":null,"abstract":"<p><strong>Aims: </strong>A 42-year-old male developed chronic primary hypoparathyroidism after total thyroidectomy. Conventional therapy led to recurrent nephrolithiasis and therefore rhPTH(1-84) (parathyroid hormone [PTH]) treatment was considered. According to the dosing guideline for PTH, calcium plasma levels are adequately controlled with once-daily administration. However, the effect on urinary calcium excretion is only transient and hence does not lower the risk of nephrolithiasis. This raises the question of whether multiple-daily or continuous administration of PTH is more effective in lowering urinary calcium excretion. We aimed to construct a pharmacokinetic-pharmacodynamic (PKPD) model to answer this question.</p><p><strong>Methods: </strong>A single patient was treated with intermittent PTH followed by off-label continuous infusion of PTH. PTH was measured in plasma, calcium and phosphate in plasma and urine. A one-compartment PKPD model for PTH was developed with Edsim++. The effect of PTH was described by the relative clearance of calcium and phosphate.</p><p><strong>Results: </strong>The PKPD model for PTH showed visually a marked effect on phosphate clearance, but less on calcium clearance. During the study, the patient also received medication that influenced calcium homeostasis but to a lesser extent phosphate homeostasis. Therefore, phosphate was chosen as the effect parameter, resulting in an EC50 of 6.3 pmol/L PTH.</p><p><strong>Conclusions: </strong>The PKPD model for PTH was completed with the unique data of a single patient who received PTH according to various dosing regimens, including continuous infusion. Continuous administration of PTH is favoured because it permanently increases the phosphate clearance and therefore needs to be further investigated.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simulation study to assess the influence of population pharmacokinetic model selection on initial dosing recommendations of vancomycin in neonates.","authors":"Mehdi El Hassani, Mathieu Blouin, Amélie Marsot","doi":"10.1111/bcp.16345","DOIUrl":"https://doi.org/10.1111/bcp.16345","url":null,"abstract":"<p><strong>Aims: </strong>The accuracy of model-informed precision dosing largely depends on selecting the most appropriate population pharmacokinetic (popPK) model from many available options. This study aims to evaluate the concordance of optimal initial simulated doses among various vancomycin popPK models developed in neonates and to explore the role of predictive performance in explaining the variability in probability of target attainment (PTA).</p><p><strong>Methods: </strong>A virtual neonatal patient population was created and 26 previously externally evaluated vancomycin popPK models were used to simulate 5 different dosing regimens. For each simulated scenario, the area under the concentration-time curve and PTA were calculated to assess the agreement on optimal initial doses across the 26 models. A multiple regression was performed to explore the impact of the models' predictive performance on PTA.</p><p><strong>Results: </strong>For most models (15/26), there was an agreement on the optimal dosing regimen. The highest PTA being achieved by the model with the best a priori predictive performance. The multiple regression model significantly predicted mean ln-transformed PTA, with F(2, 23) = 5.406 and P = .010, yielding an adjusted R² of .21. PTA was significantly influenced by imprecision (P = .048) but not bias (P = .469).</p><p><strong>Conclusion: </strong>In conclusion, our study demonstrated that, despite the variability in bias and imprecision, there was a consensus on the initial optimal doses for the majority of models; however, models with superior a priori predictive performance yielded higher PTA values. Bias and imprecision alone only seem to predict a small proportion of the variability in PTA, with imprecision having a more pronounced effect.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inter-rater agreement for detection of potentially inappropriate medication according to explicit and implicit STOPP criteria","authors":"Naldy Parodi López,&nbsp;Staffan A. Svensson,&nbsp;Susanna M. Wallerstedt","doi":"10.1111/bcp.16352","DOIUrl":"10.1111/bcp.16352","url":null,"abstract":"<p>The Screening Tool of Older Person's Prescriptions (STOPP) is used to detect potentially inappropriate medication. Version 2 includes 80 criteria, whereof two can be considered implicit as their detection primarily relies on the assessor's expertise: (A1) drugs without indication and (A2) drug treatment beyond recommended duration. To explore the inter-rater agreement for detection of explicit and implicit criteria, data on consecutive primary care patients from a previous study (<i>n</i> = 302, 65–99 years of age) were used, including independent assessments of the 78 explicit criteria (23 556 assessments) and the two implicit criteria (604 assessments) by two specialist physicians. Overall, 123 (0.5%) explicit and 10 (2%) implicit criteria were fulfilled according to both physicians. The positive agreement for a criterion being fulfilled was 56% for explicit and 16% for implicit criteria, with kappa values of 0.56 and 0.09. Discordant detection of furosemide and proton pump inhibitors was common using explicit and implicit criteria.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 2","pages":"485-490"},"PeriodicalIF":3.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of ABCB1 single-nucleotide variants on early, extremely severe neutropenia induced by paclitaxel/nanoparticle albumin-bound paclitaxel in patients with gastric cancer.","authors":"Akimitsu Maeda, Keitaro Matsuo, Hitoshi Ando, Jun-Ichi Morishige, Kei Muro, Kosaku Uchida, Masahiro Tajika","doi":"10.1111/bcp.16359","DOIUrl":"https://doi.org/10.1111/bcp.16359","url":null,"abstract":"<p><strong>Aims: </strong>Paclitaxel and nanoparticle albumin-bound (nab)-paclitaxel can cause early, extremely severe neutropenia, occasionally leading to fatal outcomes. As paclitaxel is a substrate of P-glycoprotein, this study aimed to investigate the impact of ABCB1 single-nucleotide variants, which encode P-glycoprotein, on early, extremely severe neutropenia in patients receiving paclitaxel/nab-paclitaxel plus ramucirumab as second-line therapy for unresectable advanced/recurrent gastric cancer.</p><p><strong>Methods: </strong>We analysed patients treated at Aichi Cancer Center Hospital from January 2018 to August 2023, with DNA samples stored in the Cancer BioBank Aichi. The impact of ABCB1 variants T1236C (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642) on early, extremely severe neutropenia was examined. Neutropenia was defined as a decline in neutrophil count to <100/μL within 28 days of therapy initiation. Firth's logistic regression evaluated the association between the ABCB1 C3435T (rs1045642) TT genotype and early, extremely severe neutropenia, adjusted for age, sex, baseline neutrophil count, and serum albumin and aspartate aminotransferase levels.</p><p><strong>Results: </strong>Of the 203 eligible patients, 5 (2%) experienced neutropenia with neutrophil counts of <100/μL. The odds ratio for neutrophil counts of <100/μL was 28.1 (95% confidence interval 2.8-283.3) in patients with the ABCB1 C3435T (rs1045642) TT genotype.</p><p><strong>Conclusion: </strong>The ABCB1 C3435T (rs1045642) TT genotype was significantly associated with early, extremely severe neutropenia in patients receiving paclitaxel/nab-paclitaxel. Evaluating this genotype status may help predict those at increased risk for early, extremely severe neutropenia.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of gut bile acid composition on the glucose-lowering effect and safety of metformin.","authors":"Deok Yong Yoon, Jungeun Kim, Joo-Youn Cho, Jae-Yong Chung","doi":"10.1111/bcp.16358","DOIUrl":"https://doi.org/10.1111/bcp.16358","url":null,"abstract":"<p><strong>Aims: </strong>This study evaluates how changes in intestinal bile acid composition, induced by cholestyramine, a bile acid sequestrant, affect metformin's pharmacodynamics (PD).</p><p><strong>Methods: </strong>An open-label, 2-period 1-sequence crossover study was conducted with healthy male adults. Each period consisted of both before and after metformin treatments. Cholestyramine was administered during the second period to change the bile acid pool. For, PD assessment, an oral glucose tolerance test was conducted at each treatment in both periods. Metformin was administered 3 times during each period, and cholestyramine was administered 3 times per day for 7 days during the second period. Maximum serum glucose concentration, area under the glucose concentration curve and homeostatic model assessment of insulin resistance were calculated. Baseline-corrected PD parameters were derived by subtracting pre-metformin values from post-metformin values. Lipid and panels and bile acid profiles in stool were measured. Adverse events were monitored throughout the study.</p><p><strong>Results: </strong>Fourteen subjects completed the study. The mean values of 3 PD parameters were all decreased after metformin administration in both periods. Cholestyramine administration led to a further decrease in baseline-corrected PD parameters, significantly reducing the area under the glucose concentration curve by 44.7%. Diarrhoea, the most common adverse event, was reported in 10 subjects during the metformin alone treatment and in 1 subject during the cholestyramine combined treatment (P < .01).</p><p><strong>Conclusion: </strong>Cholestyramine affected the glucose-lowering effect of metformin by the possible change in the bile acid pool in the gut, and metformin-associated diarrhoea was improved by cholestyramine.</p>","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selected Abstracts from Pharmacology 2024","authors":"","doi":"10.1111/bcp.16336","DOIUrl":"10.1111/bcp.16336","url":null,"abstract":"&lt;p&gt;&lt;b&gt;139&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Optimal safer antihypertensive drug dosing&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;Simon Dimmitt&lt;/span&gt;&lt;sup&gt;1&lt;/sup&gt;, Michael Kennedy&lt;sup&gt;2&lt;/sup&gt;, Hans Stampfer&lt;sup&gt;3&lt;/sup&gt; and Jennifer Martin&lt;sup&gt;4&lt;/sup&gt;&lt;/p&gt;&lt;p&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;i&gt;University of Western Australia;&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt;&lt;i&gt;University of New South, Wales;&lt;/i&gt; &lt;sup&gt;3&lt;/sup&gt;&lt;i&gt;Joondalup Health Campus;&lt;/i&gt; &lt;sup&gt;4&lt;/sup&gt;&lt;i&gt;University of Newcastle&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Introduction&lt;/b&gt;&lt;/p&gt;&lt;p&gt;High blood pressure (BP) affects over 30% of the population, increases with age and contributes to arterial and heart disease. Only diuretics, beta-blockers and angiotensin-converting enzyme inhibitors (ACEIs) have been shown to improve survival in large long term randomized controlled trials (RCTs). Excess BP reduction may compromise vital organ perfusion. No long-term antihypertensive drug combination has lowered BP by greater than a mean of 20/8 mmHg.&lt;/p&gt;&lt;p&gt;This pilot study aimed to ascertain sufficient doses, when best therapy is combined, to lower diastolic BP (less subject to ‘white coat effect’) in more severe hypertension (identified by ECG evidence of left ventricular hypertrophy, LVH), within the range 60–90 mmHg (which was associated with the lowest incidence of cardiovascular events in large RCTs).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Method&lt;/b&gt;&lt;/p&gt;&lt;p&gt;From a clinic pool of over 400 patients on antihypertensive drug therapy (eGFR &gt; 40 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;), 43 patients were identified with ECG LVH by voltage criteria. At 2–3 monthly visits, drugs had been added, and doses reduced as side effects became apparent. Effective dose 50 (ED50) of antihypertensive drugs was estimated as the median oral dose sufficient to lower BP by 50% of the maximum possible (Emax, ED100) and enabled dose equivalence to be determined in each drug class.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results&lt;/b&gt;&lt;/p&gt;&lt;p&gt;26 patients were excluded because of active comorbidities. 17 patients remained in the analysis (median age 72 years, 5 women). All had ECG left axis deviation and their mean clinic BP over the last 3 visits was 148/78 (heart rate 65). Systolic BP was a median of 41 mm lower than each patient's highest ever recorded. Five patients were on 2 antihypertensive drugs, nine were on 3, and three were on 4. The median observed daily doses of the 13 patients on thiazides was the equivalent of 6 mg of hydrochlorothiazide (ED50 around 20 mg), of the 13 patients on ACEIs was the equivalent of 1 mg of ramipril (ED50 3 mg), of the 12 patients on a beta-blocker was the equivalent of 7 mg metoprolol (ED50 60 mg), and of the 9 patients on a calcium channel blocker was the equivalent of 0.5 mg amlodipine (ED50 2 mg).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Moderate to severe hypertension may be controlled with 2–4 antihypertensive drugs in combination at low doses, with the potential advantages of greater tolerability and safety.&lt;/p&gt;&lt;p&gt;&lt;b&gt;141&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Efficacy of nitric oxide in stroke: Prospective randomised single blinded masked-endpoint phase IIb trial&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;span&gt;Philip Bath&lt;/span&gt;&lt;sup&gt;1,2&lt;/su","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 2","pages":"495-590"},"PeriodicalIF":3.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Between Scylla and Charybdis: Navigating heart failure management in complex older adults","authors":"Lorenz Van der Linden,&nbsp;Ross Tsuyuki","doi":"10.1111/bcp.16357","DOIUrl":"10.1111/bcp.16357","url":null,"abstract":"&lt;p&gt;Heart failure is a prevalent and high-risk clinical syndrome.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Among individuals aged 80 year and older, it affects at least 10% of the population and on geriatric hospital wards, up to 30%–35% have heart failure.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; Multiple therapies are available to prevent and manage heart failure.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Pursuing the now-standard quadruple therapy, consisting of renin-angiotensin-aldosterone system inhibitor (RAAS-I), beta blocker, sodium glucose cotransporter-2 antagonist and mineralocorticoid receptor inhibitor, in heart failure with reduced ejection fraction (HFrEF) has been estimated to at least halve all-cause mortality.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; As a result, this approach has earned a class IA recommendation in current guidelines.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Importantly, while guideline-directed medical therapies improve hard clinical outcomes, this benefit is primarily seen in ambulatory, chronic HFrEF patients, similar to those enrolled in the landmark trials. As patients deviate from this profile, the less clear the net benefit of such medical therapies on clinical outcomes becomes. Moreover, even despite the availability of trial-tested pharmacotherapy, outcomes remain suboptimal, characterized by a high residual burden, particularly following acute heart failure episodes. For instance, the 90-day mortality and hospitalization rates in the aftermath of an acute heart failure event are on average 10%–15% and 20%–25%.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Even among stable patients exhibiting ‘favourable’ heart failure phenotypes (EF &gt;40%), such as those observed in the FINEARTS HF study, outcomes were far from satisfactory, revealing a 16.4% to 17.4% rate of all-cause mortality during a median follow-up of 32 months.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;This brings us to an as yet unresolved paradox. On one hand, older adults with heart failure experience higher event rates, that is, they are at higher risk for poor outcomes. Assuming the relative efficacy of guideline-directed medical therapies holds across age groups, older adults should consequently derive larger absolute benefits in reducing mortality and heart failure hospitalizations. For instance, if the hazard ratio for heart failure hospitalizations is similar across age groups, the absolute risk reduction should be more substantial when baseline event rates are higher. On the other hand, we must acknowledge that managing heart failure in older adults presents unique challenges. Indeed, the concept of less guideline-directed medical therapies in complex older adults is not new; a lower use of ACE inhibitors in older adults with heart failure has been reported as early as 1992.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Their higher complexity and multimorbidity—including frailty—complicate the optimal use of such medical therapies and may even shift the risk–benefit balance. In this regard, the risks of symptomatic hypotension and falls are particula","PeriodicalId":9251,"journal":{"name":"British journal of clinical pharmacology","volume":"91 2","pages":"306-309"},"PeriodicalIF":3.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}