Frequency of tetrazepam prescription: estimates for Germany

PurposeAuthorisation was suspended on 1 August 2013 for tetrazepam-containing medicines. The aim of the study was to assess relevance and pattern of tetrazepam use by estimating the prevalence of prescribing and to analyse prescribing indications and duration. This information is needed to generate baseline data for further evaluation of prescribing muscle relaxants. MethodsClaims data analysis (Health Insurance Sample AOK Hesse/KV Hesse, 18.75% random sample of insurants from AOK Hesse, Germany). Study population: 267787 insurants continuously insured or deceased in 2011. Prevalence estimates were standardised to the German population. To assess the quantity of prescribed tetrazepam, we applied defined daily dose (DDD) methodology with 125mg of tetrazepam as 1 DDD. The prescribing indications were analysed with a matched case-control design. ResultsIn 2011, 2.6% of the study population received at least one tetrazepam prescription (men, 2.1%; women, 3.0%). The mean prescribed dosage was 15 DDD and increased by age up to 43 DDD in women and 30 DDD in men 80years. The most frequently documented diagnoses were low-back pain (21.3%) and cervicalgia (20.3%). It appeared that the greatest difference in prevalence between tetrazepam recipients and controls was for the diagnosis Other specified disorders of muscle' (ICD: M62.8). This diagnosis was five times more prevalent in tetrazepam recipients than in controls. ConclusionTetrazepam was the most widely prescribed muscle relaxant in Germany, hence physicians may seek an alternative after its market withdrawal. However, according to treatment guidelines, muscle relaxants play only a minor role and a multimodal approach should be preferred. Copyright (c) 2014 John Wiley & Sons, Ltd

Development, evaluation and use of COVID_19 vaccines in older adults: Preliminary principles for the pandemic and beyond

The COVID-19 pandemic brought development, evaluation and use of vaccines for older adults into the spotlight. Here, we reflect on the gaps that were highlighted and strategies to fill them, during the pandemic and beyond. This commentary draws on principles we compiled through the geriatric pharmacology subcommittee of the clinical division of the International Union of Basic and Clinical Pharmacology (IUPHAR), to guide the regulation and use of the COVID-19 vaccines for older adults.These are based on principles for evaluation and use of other therapeutics in older people

Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Introduction: We aimed to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older patients with type 2 diabetes with inadequate glycaemic control. Methods: We included randomized controlled trials (RCTs) in older (> 65 years) patients with type 2 diabetes. The intervention group was randomized to treatment with any DPP-4 inhibitors. A systematic search in MEDLINE and Embase was performed in December 2020. For assessing the risk of bias, RoB 2 tool was applied. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We pooled outcomes using random effects meta-analyses. Results: We identified 16 RCTs that included 19,317 patients with a mean age of greater than 70 years. The mean HbA1c level ranged between 7.1 and 10.0 g/dl. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly [risk ratio (RR) 1.04; 95% confidence interval (CI) 0.89-1.21]. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia (RR 1.08; 95% CI 1.01-1.16), but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas (RR 0.88; 95% CI 0.75-1.04). DPP-4 inhibitors probably reduce the risk for hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis. Conclusion: There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case second-line treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas. Plain language summary Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes Introduction: We performed the review to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older type 2 diabetes patients with blood sugar outside the normal level. Methods: To answer the question, we searched various electronic databases. We included studies in older (> 65 years) patients with type 2 diabetes that assessed the safety of DPP-4 inhibitors. The data from the different studies were quantitatively summarized using statistical methods. We assessed the quality of the data to judge the certainty of the findings. Results: We identified 16 studies that included 19,317 patients with a mean age greater than 70 years. The average blood sugar level of patients in the included studies was slightly or moderately increased. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia, but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas. DPP-4s probably reduce the risk of hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis. Conclusion: There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase the risk that blood sugar falls below normal. Adding DPP-4 inhibitorss to standard care in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case additional treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas

Describing deprescribing trials better: an elaboration of the CONSORT statement

Objective: The objective of this study was to identify key features to be addressed in the reporting of deprescribing trials and to elab-orate and explain CONSORT items in this regard. Study Design and Setting: As a first step in a multistage process and based on a systematic review of deprescribing trials, we elab-orated variation in design, intervention, and reporting of the included trials of the review. We identified items that were missed or insufficiently described, using the CONSORT and TIDieR checklists. The resulting list of items, which we considered relevant to be reported in deprescribing trials, were discussed in a single-round Delphi exercise and subsequently in a full-day face-to-face meeting with an international panel of 14 experts. We agreed on CONSORT items for further elaboration with regard to design and reporting of deprescribing trials. Results: We identified seven CONSORT items on trial design, participants, intervention, outcomes, flowchart, and harms, where the investigators of deprescribing trials should take into consideration specific aspects, such as whether or not to use placebo or how to inform participants. Conclusion: This article presents an elaboration to the CONSORT statement for the reporting of deprescribing trials. It may also support investigators in motivated design choices. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Describing deprescribing trials better:an elaboration of the CONSORT statement

Objective: The objective of this study was to identify key features to be addressed in the reporting of deprescribing trials and to elaborate and explain CONSORT items in this regard. Study Design and Setting: As a first step in a multistage process and based on a systematic review of deprescribing trials, we elaborated variation in design, intervention, and reporting of the included trials of the review. We identified items that were missed or insufficiently described, using the CONSORT and TIDieR checklists. The resulting list of items, which we considered relevant to be reported in deprescribing trials, were discussed in a single-round Delphi exercise and subsequently in a full-day face-to-face meeting with an international panel of 14 experts. We agreed on CONSORT items for further elaboration with regard to design and reporting of deprescribing trials. Results: We identified seven CONSORT items on trial design, participants, intervention, outcomes, flowchart, and harms, where the investigators of deprescribing trials should take into consideration specific aspects, such as whether or not to use placebo or how to inform participants. Conclusion: This article presents an elaboration to the CONSORT statement for the reporting of deprescribing trials. It may also support investigators in motivated design choices

Stability and ultimate behaviour of prestressed stayed beam-columns

The instability of beam-columns with crossarms and externally prestressed cable stays is studied analytically, where the combination of bending and compression is assumed to be derived from the system self-weight acting orthogonally to the applied axial load. Three principal zones of behaviour are identified with two of these each having two sub-zones that relate the critical buckling load to the initial prestressing force applied to the stay cables. The ultimate load-carrying capacity of the beam-columns is evaluated by conducting nonlinear finite element analysis within the commercial package ABAQUS. Results show that the analytically derived critical buckling loads generally provide safe predictions of the ultimate loads due to significant post-buckling strength. It is found that releasing the geometric double symmetry of the system can make for a significantly more efficient structure due to the effect of pre-cambering against the self-weight. The strength and efficiency of stayed beam-column systems opens up a range of potential applications, including lighter alternatives to conventional props to support wide excavations, which currently utilize very heavy steelwork

Anticholinergic burden measures, symptoms, and fall-associated risk in older adults with polypharmacy: Development and validation of a prognostic model.

BackgroundAnticholinergic burden has been associated with adverse outcomes such as falls. To date, no gold standard measure has been identified to assess anticholinergic burden, and no conclusion has been drawn on which of the different measure algorithms best predicts falls in older patients from general practice. This study compared the ability of five measures of anticholinergic burden to predict falls. To account for patients' individual susceptibility to medications, the added predictive value of typical anticholinergic symptoms was further quantified in this context.Methods and findingsTo predict falls, models were developed and validated based on logistic regression models created using data from two German cluster-randomized controlled trials. The outcome was defined as "≥ 1 fall" vs. "no fall" within a 6-month follow-up period. Data from the RIME study (n = 1,197) were used in model development, and from PRIMUM (n = 502) for external validation. The models were developed step-wise in order to quantify the predictive ability of anticholinergic burden measures, and anticholinergic symptoms. In the development set, 1,015 patients had complete data and 188 (18.5%) experienced ≥ 1 fall within the 6-month follow-up period. The overall predictive value of the five anticholinergic measures was limited, with neither the employed anticholinergic variable (binary / count / burden), nor dose-dependent or dose-independent measures differing significantly in their ability to predict falls. The highest c-statistic was obtained using the German Anticholinergic Burden Score (0.73), whereby the optimism-corrected c-statistic was 0.71 after interval validation using bootstrapping and 0.63 in the external validation. Previous falls and dizziness / vertigo had the strongest prognostic value in all models.ConclusionsThe ability of anticholinergic burden measures to predict falls does not appear to differ significantly, and the added value they contribute to risk classification in fall-prediction models is limited. Previous falls and dizziness / vertigo contributed most to model performance