European Journal of Clinical Pharmacology

Rindone, Joseph P.; Mellen, Chadwick K.

doi: 10.1007/s00228-024-03686-6pmid: 38597935

PurposeThe objective of this meta-analysis is to determine how sacubitril/valsartan (SV) compares to equivalent and sub-equivalent angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) in patients with heart failure with reduced ejection fraction (HFrEF).MethodsThe databases of PubMed and EMBASE were used to identify those randomized controlled trials which compared SV to ARB/ACEI in patients with HFrEF. Only those trials that reported outcomes regarding total mortality, cardiovascular mortality, and worsening heart failure were considered. Meta-analysis was performed separately in those patients receiving equivalent doses of ARB/ACEI and those receiving sub-equivalent doses. Equivalent doses were SV 97/103 = valsartan 160 mg twice daily = enalapril 20 mg twice daily = ramipril 5 mg twice daily. Meta-analyses were performed using Review Manager 5.4.ResultsTwelve randomized trials were identified involving 17,484 patients: 11,291 in the sub-equivalent group (8 trials) and 6193 in the equivalent group (4 trials). Meta-analyses showed there were no statistical differences regarding the outcomes of total mortality, cardiovascular mortality, and worsening heart failure in the equivalent dosing group. However, SV reduced total mortality (risk ratio (RR) = 0.85, 95% confidence interval (CI) = 0.78–0.93, p < 0.001), cardiovascular mortality (RR = 0.81, 95% CI = 0.73–0.90, p ≤ 0.001) and worsening heart failure (RR = 0.77, 95% CI = 0.64–0.92, p = 0.005) in the sub-equivalent group.ConclusionWhen compared to equivalent doses of ARB/ACEI, SV is not superior in reducing mortality and worsening heart failure. SV is superior when compared to sub-equivalent doses of ACEI.

de Campos, Wladimir Gushiken; Araújo, Rita; Teixeira, Vinícius; Gomes, Pedro Sousa; Lemos, Celso Augusto

doi: 10.1007/s00228-024-03693-7pmid: 38691138

PurposeThis systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation.MethodsA comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs.ResultsFrom an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight.ConclusionAlthough previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women.

van Nuland, Merel; Snoep, JaapJan D.; Egberts, Toine; Erdogan, Abdullah; Wassink, Ricky; van der Linden, Paul D.

doi: 10.1007/s00228-024-03687-5pmid: 38592470

PurposeClinical decision support systems (CDSS) are used to identify drugs with potential need for dose modification in patients with renal impairment. ChatGPT holds the potential to be integrated in the electronic health record (EHR) system to give such dosing advices. In this study, we aim to evaluate the performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal impairment.MethodsThis cross-sectional study was performed at Tergooi Medical Center, the Netherlands. CDSS alerts regarding renal dysfunction were collected from the electronic health record (EHR) during a 2-week period and were presented to ChatGPT and an expert panel. Alerts were presented with and without patient variables. To evaluate the performance, suggested medication interventions were compared.ResultsIn total, 172 CDDS alerts were generated for 80 patients. Indecisive responses by ChatGPT to alerts were excluded. For alerts presented without patient variables, ChatGPT provided “correct and identical” responses to 19.9%, “correct and different” responses to 26.7%, and “incorrect responses to 53.4% of the alerts. For alerts including patient variables, ChatGPT provided “correct and identical” responses to 16.7%, “correct and different” responses to 16.0%, and “incorrect responses to 67.3% of the alerts. Accuracy was better for newer drugs such as direct oral anticoagulants.ConclusionThe performance of ChatGPT in clinical rule-guided dose interventions in hospitalized patients with renal dysfunction was poor. Based on these results, we conclude that ChatGPT, in its current state, is not appropriate for automatic integration into our EHR to handle CDSS alerts related to renal dysfunction.

Huang, Xinhai; Xu, Wenlin; Wu, Guilan; Li, Ruijuan; Gu, Ping; Zheng, Qiaowei; Liu, Xiumei; Dai, Hengfen; Lin, Xiangsheng; Liu, Yuxin; Du, Xiaoming; Su, Jun; Zhang, Wang; Zhang, Min; Zhu, Zhu; Huang, Xiaohong;

Abedi, Farshad; Zarei, Batool; Elyasi, Sepideh

doi: 10.1007/s00228-024-03664-ypmid: 38607390

PurposeNowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration.MethodsData collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication.ResultsA total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation.ConclusionAlbumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin.

Noda, Aoi; Obara, Taku; Shirota, Matsuyuki; Ueno, Fumihiko; Matsuzaki, Fumiko; Hatanaka, Rieko; Obara, Ryo; Morishita, Kei; Shinoda, Genki; Orui, Masatsugu; Murakami, Keiko; Ishikuro, Mami; Kuriyama, Shinichi

doi: 10.1007/s00228-024-03685-7pmid: 38630193

PurposeTo elucidate the status of medication use among pregnant women in Japan, by means of a multigenerational genome and birth cohort study: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study).MethodsQuestionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (from July 2013 to March 2017) around 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed medication use over three periods: (1) 12 months prior to pregnancy diagnosis, (2) the period between pregnancy diagnosis and around week 12 of pregnancy, and (3) post around week 12 of pregnancy.ResultsIn total, 19,297 women were included in the analysis. The proportion of pregnant women using medications was 49.0% prior to pregnancy diagnosis, 52.1% from diagnosis to week 12, and 58.4% post week 12 of pregnancy. The most frequently prescribed medications were loxoprofen sodium hydrate (5.5%) prior to pregnancy diagnosis, magnesium oxide (5.9%) from diagnosis to week 12, and ritodrine hydrochloride (10.5%) post week 12 of pregnancy. The number of women who used suspected teratogenic medications during early pregnancy was 96 prior to pregnancy diagnosis, 48 from diagnosis to week 12, and 54 post week 12 of pregnancy.ConclusionWe found that ~ 50% of the pregnant women used medications before and during pregnancy and some took potential teratogenic medications during pregnancy. In birth genomic cohort study, it is expected that investigations into the safety and effectiveness of medications used during pregnancy will advance.

Yang, Xiding; Yan, Qiangyong; Yang, Lingfeng; Li, Jingjing; Fan, Xiao; Chen, Jindong; Wu, Haishan; Yang, Yongyu; Zhu, Ronghua; Fang, Pingfei

doi: 10.1007/s00228-024-03690-wpmid: 38639762

Arnet, Isabelle; Eickhoff, Christiane; Sahm, Laura J; Caloz, Sabine; Mittag, Michael; Schulz, Martin; Allemann, Samuel S

doi: 10.1007/s00228-024-03684-8pmid: 38647703

PurposeTo propose a paradigm change for the validation procedures of medication adherence questionnaires.MethodsA total of 121 validation procedures of unique questionnaires for medication adherence were analyzed.Results“Construct validity” and “internal consistency” were most often assessed, and test results varied largely. A more in-depth analysis indicated that the assessment of medication non-adherence included distinct but related constructs, such as the extent to which doses are missed, and the attempt to identify different facets of medication-taking behavior. Consequently, each construct requires a different measurement approach with different psychometric tests for establishing its validity and reliability.ConclusionResults show that assessing the validity and reliability of adherence questionnaires with standard procedures including statistical tests is inconclusive. Refinement of the constructs of non-adherence is needed in pharmacy and medical practice. We suggest a distinction between the (i) extent of missed doses over the past 2 weeks, (ii) modifiable reasons for non-adherence behavior, and (iii) unmodifiable factors of non-adherence. Validation procedures and corresponding statistical methods should be selected according to the specific single constructs.

Möller, Finja; Oetting, Malte; Spiegel, Andreas; Zube, Olaf; Bertsche, Thilo

doi: 10.1007/s00228-024-03682-wpmid: 38656416

PurposeIn many countries, outpatient and inpatient care are separated. During hospitalization, therefore, switching the outpatient medication to medication of the hospital formulary is required.MethodsWe newly designed a switching algorithm in six switching steps (S0–S5) and conducted a study at Bundeswehr Hospital Hamburg (300 beds, 80% civilians). We performed (i) a medication reconciliation to obtain information on outpatient medications and (ii) a medication review to solve drug-related-problems, e.g., drug-drug interactions. We applied (iii) the algorithm to switch medications to the hospital formulary.Results(i) We identified 475 outpatient medications (median per patient: 4; Q25/Q75 2/7) in 100 patients consecutively admitted to hospital (median age: 71; Q25/Q75: 64/80 years). Of 475 medications, the switching algorithm could not be used since product names were missing in 23.9% and strength in 1.7%. In 3.2%, switching was not required since medication was not prescribed during the hospital stay. (ii) Drug-drug interactions were identified in 31 of 79 patients with more than one medication. (iii) Of 475 medications, 18.5% were on the hospital formulary and therefore did not need to be  switched (S0), 0.2% were on a substitution-exclusion list not allowing switching (S1), 42.0% were switched to a generic medication of the hospital formulary (S2), 1.7% to a therapeutically equivalent medication (S3), 0.4% were patient-individually switched (S4), and for 8.2% a standardized/patient-individual switching was not possible (S5).ConclusionsDespite comprehensive medication reconciliation, patient- and medication-related information for switching medications to the hospital formulary was often missing. Once all the necessary information was available, standardized switching could be easily carried out according to a newly developed switching algorithm.

Holmberg, Henrik; Glader, Eva-Lotta; Näslund, Ulf; Carlberg, Bo; Sönnerstam, Eva; Norberg, Margareta; Själander, Anders

doi: 10.1007/s00228-024-03694-6pmid: 38684558

BackgroundPeople with intermediate CVD risk constitute most of the population. Within this group, the proportion of events is lower compared to the high-risk group, but they contribute with the largest absolute number of events. Atherosclerosis is a dynamic process and progression can be slowed or even reversed with medication and lifestyle changes, but adherence to prescribed treatment is crucial.AimTo investigate the long-term effects of interventions with pictorial risk communication of cardiovascular (CVD) risk on average adherence in a group of statin users. Compare response in adherence over time between men and women after intervention.MethodsParticipants on active statin treatment were followed up to 5 years after being randomly assigned to an intervention program aimed at raising CVD risk awareness among participants and their physicians. Merging prescribed medication databases with VIPVIZA study to study adherence over time. A moving average adherence was used to compare groups.ResultsGenerally, the average adherence to statins among the 512 participants was high. Men had a higher average adherence over time, while women had a sharper increase in adherence in conjuncture with the intervention program.ConclusionsBoth men and women were receptive to pictorial information regarding CVD risk, but the intervention effect was more pronounced in women. Sex differences are important when considering risk communication strategies. Periodically repeating the intervention was beneficial for maintaining the intervention effect over time.Trial registrationThe VIPVIZA study is registered with ClinicalTrials.gov, May 8, 2013, number NCT01849575.