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Potentially Inappropriate Medication Use in Primary Care in Switzerland.
Get PDFIMPORTANCE
Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing.
OBJECTIVE
To determine PIM prevalence and the most frequently prescribed PIMs according to 6 well-known PIM lists and to develop a best practice synthesis for clinicians.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used anonymized electronic health record data of Swiss primary care patients aged 65 years or older with drug prescriptions from January 1, 2020, to December 31, 2021, extracted from a large primary care database in Switzerland, the FIRE project. Data analyses took place from October 2022 to September 2023.
EXPOSURE
PIM prescription according to PIM criteria operationalized for use with FIRE data.
MAIN OUTCOMES AND MEASURES
The primary outcomes were PIM prevalence (percentage of patients with 1 or more PIMs) and PIM frequency (percentage of prescriptions identified as PIMs) according to the individual PIM lists and a combination of all 6 lists. The PIM lists used were the American 2019 Updated Beers criteria, the French list by Laroche et al, the Norwegian General Practice Norwegian (NORGEP) criteria, the German PRISCUS list, the Austrian list by Mann et al, and the EU(7) consensus list of 7 European countries.
RESULTS
This study included 115 867 patients 65 years or older (mean [SD] age, 76.0 [7.9] years; 55.8% female) with 1 211 227 prescriptions. Among all patients, 86 715 (74.8%) were aged 70 years or older, and 60 670 (52.4%) were aged 75 years or older. PIM prevalence among patients 65 years or older was 31.5% (according to Beers 2019), 15.4% (Laroche), 16.1% (NORGEP), 12.7% (PRISCUS), 31.2% (Mann), 37.1% (EU[7]), and 52.3% (combined list). PIM prevalence increased with age according to every PIM list (eg, according to Beers 2019, from 31.5% at age 65 years or older to 37.4% for those 75 years or older, and when the lists were combined, PIM prevalence increased from 52.3% to 56.7% in those 2 age groups, respectively). PIM frequency was 10.3% (Beers 2019), 3.9% (Laroche), 4.3% (NORGEP), 2.4% (PRISCUS), 6.7% (Mann), 9.7% (EU[7]), and 19.3% (combined list). According to the combined list, the 5 most frequently prescribed PIMs were pantoprazole (9.3% of all PIMs prescribed), ibuprofen (6.9%), diclofenac (6.3%), zolpidem (4.5%), and lorazepam (3.7%). Almost two-thirds (63.5%) of all PIM prescriptions belonged to 5 drug classes: analgesics (26.9% of all PIMs prescribed), proton pump inhibitors (12.1%), benzodiazepines and benzodiazepine-like drugs (11.2%), antidepressants (7.0%), and neuroleptics (6.3%).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults aged 65 or older, PIM prevalence was high, varied considerably depending on the criteria applied, and increased consistently with age. However, only few drug classes accounted for the majority of all prescriptions that were PIM according to any of the 6 PIM lists, and by considering this manageable number of drug classes, clinicians could essentially comply with all 6 PIM lists. These results raise awareness of the most common PIMs and emphasize the need for careful consideration of their risks and benefits and targeted deprescribing
Treatment outcome according to genetic tumour alterations and clinical characteristics in digestive high-grade neuroendocrine neoplasms.
Get PDFBACKGROUND
Chemotherapy has limited efficacy in advanced digestive high-grade neuroendocrine neoplasms (HG-NEN) and prognosis is dismal. Predictive markers for palliative chemotherapy are lacking, and prognostic markers are limited.
METHODS
Digestive HG-NEN patients (n = 229) were prospectively included 2013-2017. Pathological re-assessment revealed 188 neuroendocrine carcinomas (NEC) and 41 neuroendocrine tumours (NET G3). Tumour-DNA was sequenced across 360 cancer-related genes, assessing mutations (mut) and copy number alterations. We linked sequencing results to clinical information and explored potential markers for first-line chemotherapy efficacy and survival.
RESULTS
In NEC given cis/carboplatin and etoposide (PE), TP53mut predicted inferior response rate in multivariate analyses (p = 0.009) and no BRAFmut NEC showed response. In overall assessment of PE-treated NEC, no genetic alterations were prognostic for OS. For small-cell NEC, TP53mut were associated with longer OS (p = 0.011) and RB1 deletions predicted lack of immediate-progression (p = 0.003). In non-small cell NEC, APC mut were associated with immediate-progression and shorter PFS (p = 0.008/p = 0.004). For NET G3, ATRXmut, ARID1A- and ERS1 deletions were associated with shorter PFS.
CONCLUSION
Correlations between genetic alterations and response/immediate-progression to PE were frequent in NEC but affected PFS or OS only when subdividing for cell-type. The classification of digestive NEC into large- and small-cell seems therefore molecularly and clinically relevant
Clinical spectrum of human STAR variants and their genotype-phenotype correlation.
No full textBiallelic variants of steroidogenic acute regulatory protein (STAR/STARD1) may cause primary adrenal insufficiency and 46,XY disorder of sex development. STAR plays a pivotal role in transporting cholesterol into mitochondria where cholesterol serves as essential substrate for initiating steroid biosynthesis by its conversion to pregnenolone. Generally, loss-of-function mutations of STAR cause the classic form of lipoid Congenital Adrenal Hyperplasia (LCAH) where steroidogenesis of the adrenal cortex and the gonads is severely affected. By contrast, partial activity of STAR causes a less severe phenotype, the non-classic LCAH, which is characterized by later onset and initial manifestation with isolated adrenal insufficiency only. Disease causing STAR variants are very rare. Numerous variants of all types have been described worldwide. Prevailing variants have been reported from Japan and Korea and in some population clusters where STAR is more common. Genotype-phenotype correlation is pretty good for STAR variants. While the exact mechanisms of cholesterol transport into mitochondria for steroidogenesis are still under investigation, the important role of STAR in this process is evident by inactivating STAR variants causing LCAH. The mechanism of disease with STAR deficiency is best described by a two hit model: The first hit relates to impaired cholesterol import into mitochondria and thus lack of substrate for all steroid hormone biosynthesis. The second hit then relates to massive cytoplasmic lipid overload (evidenced by typically enlarged and fatty adrenal glands) leading to cell death and organ destruction. This review summarizes phenotype and genotype characteristics of human STAR variants found through the ClinVar database
Non-invasive brain stimulation for treatment-resistant schizophrenia: protocol of a systematic review and network meta-analysis.
Get PDFBACKGROUND
Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS
We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
DISCUSSION
Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42023410645
Unobtrusive measurement of gait parameters using seismographs: An observational study.
Get PDFAnalyzing irregularities in walking patterns helps detect human locomotion abnormalities that can signal health changes. Traditional observation-based assessments have limitations due to subjective biases and capture only a single time point. Ambient and wearable sensor technologies allow continuous and objective locomotion monitoring but face challenges due to the need for specialized expertise and user compliance. This work proposes a seismograph-based algorithm for quantifying human gait, incorporating a step extraction algorithm derived from mathematical morphologies, with the goal of achieving the accuracy of clinical reference systems. To evaluate our method, we compared the gait parameters of 50 healthy participants, as recorded by seismographs, and those obtained from reference systems (a pressure-sensitive walkway and a camera system). Participants performed four walking tests, including traversing a walkway and completing the timed up-and-go (TUG) test. In our findings, we observed linear relationships with strong positive correlations (R2 > 0.9) and tight 95% confidence intervals for all gait parameters (step time, cycle time, ambulation time, and cadence). We demonstrated that clinical gait parameters and TUG mobility test timings can be accurately derived from seismographic signals, with our method exhibiting no significant differences from established clinical reference systems
Mental health and the ballot box: A correlational analysis of Google searches for mental health and national election periods in the United States and the United Kingdom from 2008 to 2020.
No full textBACKGROUND
In electoral contexts, mental health topics have recently attracted sociopolitical relevance, influenced by policy developments, election-related psychopathology and popular discourse about individual candidates. Yet, whether this reflects generalised trends or is contingent on election-specific and contextual factors remains difficult to ascertain.
AIMS
This study sought to examine correlations between Google Trends (GT) data on mental health and four national elections in the US and the UK from 2008 to 2020. This was intended to yield preliminary insights into the relevance of mental health topics amongst voters and the potential impact of electoral cycles on patterns of online engagement with these issues.
METHODS
Monthly and daily Search Volume Indexes (SVI) were gathered from the 'Mental Health' category on GT in the US and UK from 2008 to 2023. SVI were evaluated around the past four national ballots, comparing election-year intervals and baseline data from the preceding year. Statistical tests were conducted to assess SVI and short- and long-term dynamics.
FINDINGS
The results showed heterogeneous SVI patterns related to mental health during elections in the US and the UK. In the US, there were statistically significant SVI increases proximal to the majority of elections as compared to data in the same calendar year, but these did not typically exceed baseline SVI. However, interestingly, divisive US contests showed correlations with several elevated SVI measures in the same and previous years. Conversely, there was a lack of consistent longitudinal trends in UK elections, perhaps informed by its disparate sociopolitical landscape.
CONCLUSIONS
These findings underline the composite relationship between electoral politics and popular engagement with mental health topics around national votes, suggesting that this is driven more by situational factors rather than a recurrent electoral effect or signs of burgeoning engagement. Detailed research is required to understand the nuances and causality behind these dynamics and their wider implications
Feasibility Study on Atrial Fibrillation Ablation with Pulsed Field Ablation and concomitant Occlusion of the Left Atrial Appendage.
Get PDFBACKGROUND AND AIMS
Atrial fibrillation (AF) ablation and left atrial appendage occlusion (LAAO) are increasingly performed as individual procedures. Pulsed field ablation (PFA) has significantly reduced procedure duration and may be advantageous for the combined approach.
METHODS
We have launched a program for simultaneous AF ablation using PFA and LAAO for patients qualifying for both treatments and excluding those with complex anatomy. We compare procedure duration and fluoroscopy time against individual procedures (either AF ablation or LAAO alone), all performed by the same operators and using consistent technologies.
RESULTS
We performed the combined procedure in 10 patients (50% male; median age 70 years) and excluded two patients (17%) because of complex LAA anatomy. No death, stroke or major bleeding, including pericardial effusion, occurred. For single procedure comparison, 207 AF ablation procedures and 61 LAAO procedures were available. Total median procedure duration was 79 minutes (range 60; 125) for the combined procedure, 71 minutes (25; 241) for individual AF ablation (51 minutes without and 78 minutes with 3D electroanatomic mapping) and 47 minutes (15; 162) for individual LAAO. Respective fluoroscopy times were 21 (15; 26), 15 (5; 44) and 10 (3; 50) minutes. For the combined procedure, femoral vein access to last PFA application lasted 49 minutes (34; 93) and LAAO added 20 minutes (15; 37).
CONCLUSION
Simultaneous PFA-based AF ablation and LAAO in carefully selected patients is feasible, safe, and can be executed within a short overall procedure duration
Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study.
No full textWe aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries
Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle.
Get PDFHepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV's imprint on cell metabolism
600 years of wine must quality and April to August temperatures in western Europe 1420–2019
Get PDFThis study investigates the validity of wine must quality as an April-to-August temperature proxy be- tween 1420 and 2019 based on expert ratings and quality measurements from Germany, Luxembourg, eastern France, and the Swiss Plateau. This is highly relevant as uncertainties remain on past climate variations during this period. The ev- idence was reviewed according to the best practice of histor- ical climatology. Expert ratings tended to agree with Oech- sle density measurements that gradually replaced them from the 1840s. A statistical model calibrated to predict wine must quality from climate data explains 75 % of the variance, un- derlining the potential value of wine must quality as a cli- mate proxy. Premium crops were collected in years of early harvest involving high insolation during maturation, while poor crops resulted from very late harvests in cold and wet summers. An analysis of daily weather types for high- and low-quality years after 1763 shows marked differences. On a decadal timescale, the average quality was highest from 1470 to 1479, from 1536 to 1545, and from 1945 to 1954. Poor crops were collected in periods with prevailing cold and wet summers such as 1453 to 1466, 1485 to 1494, 1585 to 1614, 1685 to 1703, 1812 to 1821, and 1876 to 1936. In the pe-riod of enhanced warming after 1990, high quality became the rule
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