JAMA. 2023 Nov 7;330(17):1653-1665. doi: 10.1001/jama.2023.19761.

ABSTRACT

IMPORTANCE: Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.

OBJECTIVE: To compare efficacy and comparative efficacy of therapies for alcohol use disorder.

DATA SOURCES: PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.

STUDY SELECTION: For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.

DATA EXTRACTION AND SYNTHESIS: Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.

MAIN OUTCOMES AND MEASURES: The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.

RESULTS: Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.

CONCLUSIONS AND RELEVANCE: In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.

PMID:37934220 | DOI:10.1001/jama.2023.19761

J Addict Med. 2023 Nov-Dec 01;17(6):691-694. doi: 10.1097/ADM.0000000000001216. Epub 2023 Aug 10.

ABSTRACT

OBJECTIVES: Xylazine is an α 2 -agonist increasingly prevalent in the illicit drug supply. Our objectives were to curate information about xylazine through social media from people who use drugs (PWUDs). Specifically, we sought to answer the following: (1) What are the demographics of Reddit subscribers reporting exposure to xylazine? (2) Is xylazine a desired additive? And (3) what adverse effects of xylazine are PWUDs experiencing?

METHODS: Natural language processing (NLP) was used to identify mentions of "xylazine" from posts by Reddit subscribers who also posted on drug-related subreddits. Posts were qualitatively evaluated for xylazine-related themes. A survey was developed to gather additional information about the Reddit subscribers. This survey was posted on subreddits that were identified by NLP to contain xylazine-related discussions from March 2022 to October 2022.

RESULTS: Seventy-six posts were extracted via NLP from 765,616 posts by 16,131 Reddit subscribers (January 2018 to August 2021). People on Reddit described xylazine as an unwanted adulterant in their opioid supply. Sixty-one participants completed the survey. Of those who disclosed their location, 25 of 50 participants (50%) reported locations in the Northeastern United States. The most common route of xylazine use was intranasal use (57%). Thirty-one of 59 (53%) reported experiencing xylazine withdrawal. Frequent adverse events reported were prolonged sedation (81%) and increased skin wounds (43%).

CONCLUSIONS: Among respondents on these Reddit forums, xylazine seems to be an unwanted adulterant. People who use drugs may be experiencing adverse effects such as prolonged sedation and xylazine withdrawal. This seemed to be more common in the Northeast.

PMID:37934533 | DOI:10.1097/ADM.0000000000001216

Cardiovasc Res. 2023 Nov 2:cvad141. doi: 10.1093/cvr/cvad141. Online ahead of print.

ABSTRACT

AIMS: Cardiotoxicity is one major reason why drugs do not enter or are withdrawn from the market. Thus, approaches are required to predict cardiotoxicity with high specificity and sensitivity. Ideally, such methods should be performed within intact cardiac tissue with high relevance for humans and detect acute and chronic side effects on electrophysiological behaviour, contractility, and tissue structure in an unbiased manner. Herein, we evaluate healthy pig myocardial slices and biomimetic cultivation setups (BMCS) as a new cardiotoxicity screening approach.

METHODS AND RESULTS: Pig left ventricular samples were cut into slices and spanned into BMCS with continuous electrical pacing and online force recording. Automated stimulation protocols were established to determine the force-frequency relationship (FFR), frequency dependence of contraction duration, effective refractory period (ERP), and pacing threshold. Slices generated 1.3 ± 0.14 mN/mm2 force at 0.5 Hz electrical pacing and showed a positive FFR and a shortening of contraction duration with increasing pacing rates. Approximately 62% of slices were able to contract for at least 6 days while showing stable ERP, contraction duration-frequency relationship, and preserved cardiac structure confirmed by confocal imaging and X-ray diffraction analysis. We used specific blockers of the most important cardiac ion channels to determine which analysis parameters are influenced. To validate our approach, we tested five drug candidates selected from the Comprehensive in vitro Proarrhythmia Assay list as well as acetylsalicylic acid and DMSO as controls in a blinded manner in three independent laboratories. We were able to detect all arrhythmic drugs and their respective mode of action on cardiac tissue including inhibition of Na+, Ca2+, and hERG channels as well as Na+/Ca2+ exchanger.

CONCLUSION: We systematically evaluate this approach for cardiotoxicity screening, which is of high relevance for humans and can be upscaled to medium-throughput screening. Thus, our approach will improve the predictive value and efficiency of preclinical cardiotoxicity screening.

PMID:37934066 | DOI:10.1093/cvr/cvad141

Clin Nutr. 2023 Oct 31:S0261-5614(23)00350-3. doi: 10.1016/j.clnu.2023.10.023. Online ahead of print.

NO ABSTRACT

PMID:37932206 | DOI:10.1016/j.clnu.2023.10.023

Expert Opin Drug Metab Toxicol. 2023 Jul-Dec;19(11):829-847. doi: 10.1080/17425255.2023.2278676. Epub 2023 Nov 17.

ABSTRACT

INTRODUCTION: Antiseizure medications (ASMs) and antipsychotic drugs are frequently coadministered with the potential for drug-drug interactions. Interactions may either be pharmacokinetic or pharmacodynamic, resulting in a decrease or increase in efficacy and/or an increase or decrease in adverse effects.

AREAS COVERED: The clinical evidence for pharmacokinetic and pharmacodynamic interactions between ASMs and antipsychotics is reviewed based on the results of a literature search in MEDLINE conducted in April 2023.

EXPERT OPINION: There is now extensive published evidence for the clinical importance of interactions between ASMs and antipsychotics. Enzyme-inducing ASMs can decrease blood concentrations of many of the antipsychotics. There is also evidence that enzyme-inhibiting ASMs can increase antipsychotic blood concentrations. Similarly, there is limited evidence showing that antipsychotic drugs may affect the blood concentrations of ASMs through pharmacokinetic interactions. There is less available evidence for pharmacodynamic interactions, but these can also be important, as can displacement from protein binding. The lack of published evidence for an interaction should not be interpreted as meaning that the given interaction does not occur; the evidence is building continually. There is no substitute for careful patient monitoring and sound clinical judgment.

PMID:37925741 | DOI:10.1080/17425255.2023.2278676

Jpn J Radiol. 2023 Nov 6. doi: 10.1007/s11604-023-01505-z. Online ahead of print.

ABSTRACT

Obtaining an imaging diagnosis of various hepatobiliary and pancreatic disorders caused by certain drugs can often be challenging. Familiarity with these conditions may improve diagnostic accuracy and patient management. This review aimed to describe the imaging findings of drug-associated hepatobiliary and pancreatic disorders and identify suggestions for obtaining a correct diagnosis. We focused on relatively common disorders or those that can present with characteristic imaging findings, such as drug-induced acute hepatitis, sinusoidal obstruction syndrome, focal nodular hyperplasia-like lesions, hepatocellular adenoma, pseudocirrhosis, chemotherapy-associated steatohepatitis, amiodarone deposition in the liver, secondary iron overload, drug-induced pancreatitis, pancreatic enlargement after epoprostenol therapy, ceftriaxone-associated gallbladder pseudolithiasis, immune-related adverse events, and methotrexate-associated lymphoproliferative disorders.

PMID:37926781 | DOI:10.1007/s11604-023-01505-z

BMC Med Educ. 2023 Nov 3;23(1):829. doi: 10.1186/s12909-022-03858-x.

ABSTRACT

BACKGROUND: The Covid-19 pandemic has resulted in many student populations learning online in lockdown. While the mental health consequences of lockdown are increasingly understood, the core features of 'cabin fever' - the experience of lockdown - are poorly described.

METHODS: We conducted a questionnaire survey of 649 undergraduate medicine and health sciences students. Item content was developed based on current literature and input from student representatives.

RESULTS: Mokken scaling identified seven questions that together formed a strongly unidimensional scale which comprised two domains: social isolation/cabin fever and demotivation / demoralisation. Scale scores were significantly associated with depression, self-rated mental health, impaired study efficacy and doomscrolling.

CONCLUSIONS: The adverse effects of lockdown on student wellbeing appear to be driven to an important extent by an experience of isolation and demotivation that corresponds to narrative descriptions of cabin fever. In the foreseeable event of future pandemics, these experiences are a promising target for health promotion in students studying in lockdown.

PMID:37924033 | DOI:10.1186/s12909-022-03858-x

BMC Emerg Med. 2023 Nov 4;23(1):130. doi: 10.1186/s12873-023-00898-4.

ABSTRACT

BACKGROUND: Analgesia is a core intervention in emergency medicine. Pain is subjective, so patient-reported experience with pain and analgesia is essential for healthcare professionals. The aim of this study was to evaluate patient-reported side effects and satisfaction associated with pre-hospital analgesia with low-dose esketamine.

METHODS: This is an observational cross-sectional study conducted as part of quality assurance measures of the German Red Cross Emergency Medical Service, Reutlingen, Germany. The survey was administered to all patients who received prehospital esketamine analgesia from paramedics. Addresses were obtained from medical records and mailed 10 days after the event. Patient feedback was anonymous and could not be linked to operational documentation.

RESULTS: A total of 201 patients were contacted, and 119 responses were received via the online questionnaire and postal mail (response rate 59%). The mean age of the patients was 68±13 years, with 64.7% (n=77) being female. The main diagnosis reported was fractures of the extremities in 69.7%. Patients reported initial median pain intensity on a Numeric Rating Scale (NRS) of 10 [8-10]. Pain was unbearable for 96.3% of patients. After administration of analgesia, 95.3% were satisfied or very satisfied. Patients reported no side effects in 78.5%, minor side effects in 10.0%, significant but well tolerable side effects in 11.3%, borderline tolerable side effects in 0.2%, and no unbearable side effects. Borderline tolerable nausea was reported in 2% of patients along with dreams in 0.8%. No nightmares were reported. Further analysis showed that patients older than 80 years reported significantly more side effects (p < 0.001) and were thus less satisfied with the analgesia.

CONCLUSIONS: Both patient perception and analgesia with few side effects were important for both safety and satisfaction. In the present study, low-dose esketamine analgesia was associated with low side effects and high patient satisfaction.

PMID:37924027 | DOI:10.1186/s12873-023-00898-4

BMJ. 2023 Nov 2;383:p2545. doi: 10.1136/bmj.p2545.

NO ABSTRACT

PMID:37918837 | DOI:10.1136/bmj.p2545

Nephrol Ther. 2023 Nov 2;19(6):491-496. doi: 10.1684/ndt.2023.44.

ABSTRACT

OBJECTIVE: Data about efficacy and safety of the latest COVID-19 treatments as nirmatrelvir/ritonavir (n/r) or Sotrovimab is scarce in solid organ transplant recipients in the Omicron era. This study aims at describing the outcome of kidney transplant recipients (KTRs) presenting Omicron infection according to their management: n/r, sotrovimab or no specific treatment.

PATIENTS AND METHODS: We conducted a monocentric, retrospective observational study, including KTRs diagnosed Omicron infection between January and May 1st 2022 and compared their outcome (primary outcome defined as hospital admission for COVID-19 within a month after symptoms onset) according to early COVID-19 management.

RESULTS: Forty-five patients were included: 22 treated (12 n/r, 10 sotrovimab) and 23 with no specific treatment. The groups were statistically comparable. Two patients were admitted for COVID-19: one in each group, resulting in a non-different probability of the primary outcome at on month (p=0.9). Three patients presented tacrolimus overdose including two with acute kidney injury.

CONCLUSIONS: There was no difference in outcome according to early therapeutic management: n/r, sotrovimab or no specific treatment. Our study both underlines a decreased severity of Omicron COVID-19 in KTRs (probably related to vaccinal immunity and decreased virulence of Omicron) and a potential severe adverse effects with n/r.

PMID:37915200 | DOI:10.1684/ndt.2023.44

Acta Med Indones. 2023 Jul;55(3):277-284.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is often accompanied by a variety of comorbidities that require several medications thus, polypharmacy is unavoidable. One of the consequences of polypharmacy is the occurrence of potential drug-drug interactions (DDI). The aim of this study is to evaluate the profile of DDI in pre-dialysis CKD patients and to identify the possible adverse drug reactions (ADR) due to DDI.

METHODS: This cross-sectional study includes stage 3-5 pre-dialysis CKD patients at a referral hospital in Indonesia in 2019 - 2020. Data were collected from the electronic health record and the hospital's medical record. The prescriptions were analysed for potential DDI using Micromedex software and ADRs assessment through clinical symptoms and laboratory data abnormalities.

RESULTS: A total of 106 patients were included in the study, around 60 (56.6%) patients received more than six medications. There were 111 types of medications prescribed with the most frequently prescribed drug was bisoprolol (36.5%). The proportion of patients who received treatment with a potential DDI was 76% (81 patients), while the proportion of patients who experienced ADR was 28% (23 patients). The most prevalent ADRs were hyperglycaemia, hypertension, hyperkalaemia, and hypotension. Cardiovascular disease had a statistically significant relationship with ADR suspected due to DDI (p = 0.03).

CONCLUSION: A significant number of potential DDI were seen in the prescriptions of stage 3-5 pre-dialysis CKD patients at a referral hospital in Indonesia between 2019 - 2020. Cardiovascular disease was identified as the most common risk factor for ADR suspected caused by DDI.

PMID:37915149

Sci Rep. 2023 Nov 1;13(1):18817. doi: 10.1038/s41598-023-46275-w.

ABSTRACT

External factors severely affecting in a short period of time the spontaneous reporting of adverse events (AEs) can significantly impact drug safety signal detection. Coronavirus disease 2019 (COVID-19) represented an enormous challenge for health systems, with over 767 million cases and massive vaccination campaigns involving over 70% of the worldwide population. This study investigates the potential masking effect on certain AEs caused by the substantial increase in reports solely related to COVID-19 vaccines within various spontaneous reporting systems (SRSs). Three SRSs were used to monitor AEs reporting before and during the pandemic, namely, the World Health Organisation (WHO) global individual case safety reports database (VigiBase®), the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER). Findings revealed a sudden over-reporting of 35 AEs (≥ 200%) during the pandemic, with an increment of the RRF value in 2021 of at least double the RRF reported in 2020. This translates into a substantial reduction in signals of disproportionate reporting (SDR) due to the massive inclusion of COVID-19 vaccine reports. To mitigate the masking effect of COVID-19 vaccines in post-marketing SRS analyses, we recommend utilizing COVID-19-corrected versions for a more accurate assessment.

PMID:37914862 | DOI:10.1038/s41598-023-46275-w

G Ital Nefrol. 2023 Aug 31;40(4):2023-vol4.

ABSTRACT

Tubulointerstitial nephritis is a common cause of acute renal failure, in two thirds of cases it is associated with drugs (mostly antimicrobials and NSAIDs), in 5-10% of cases it is associated with infections (bacterial/viral/parasitic), in 5-10% of cases it is idiopathic (this is the case of the TINU syndrome characterized by interstitial nephritis and bilateral uveitis, and the anti-glomerular basal membrane antibody syndrome), and finally in 10% of cases it is associated with systemic diseases (sarcoidosis, by Sjogren, LES). The pathogenesis is based on a cell-mediated immune response and in most cases removing the causative agent is the gold standard of therapy. However, a percentage of patients, in a variable range from 30% to 70% of cases, do not fully recover renal function, due to the rapid transformation of the interstitial cell infiltrate into vast areas of fibrosis. Clozapine is a second generation atypical antipsycothic usually used for the treatment of schizophrenia resistant to other types of treatment; it can cause severe adverse effects among which the best known is a severe and potentially fatal neutropenia, furthermore a series of uncommon adverse events are recognized including hepatitis, pancreatitis, vasculitis. Cases of acute interstitial tubular nephritis associated with the use of clozapine have been described in the literature, although this complication is rare. Medical personnel using this drug need to be aware of this potential and serious side effect. We describe the case of a 48-year-old man who developed acute renal failure after initiation of clozapine.

PMID:37910212

Anticancer Res. 2023 Nov;43(11):5051-5059. doi: 10.21873/anticanres.16704.

ABSTRACT

BACKGROUND/AIM: Chemotherapy is the standard treatment for patients with unresectable gastric cancer (UGC); however, the survival outcomes are poor. This study investigated the predictive values of skeletal muscle mass (SMM) index (SMI) before second-line chemotherapy and the survival outcomes of patients with UGC.

PATIENTS AND METHODS: A total of 79 patients diagnosed with UGC at our hospital who received at least second-line palliative chemotherapy were included. The cross-sectional SMM at the third lumbar vertebra was obtained before second-line chemotherapy. SMI was defined as the muscle area normalized by height squared (m2), and SMI before second-line chemotherapy was defined as 2ndSMI.

RESULTS: Using 2ndSMI for men and women (35.4 and 31.7 cm2/m2, respectively) as the cutoff value, patients were divided into high (2ndSMIHigh; n=54) and low (2ndSMILow; n=25) 2ndSMI groups. The number of patients receiving fourth-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.039). The overall survival time after the start of second-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.008). The incidence of grade 3 or 4 side effects was significantly higher in the 2ndSMILow than in the 2ndSMIHigh group (p=0.028). The multivariate analysis identified 2ndSMI as independent prognostic factor after the start of second-line chemotherapy.

CONCLUSION: The 2ndSMILow group had a significantly worse prognosis and significantly less conversion to fourth-line chemotherapy than the 2ndSMIHigh group. Moreover, 2ndSMILow was associated with grade 3 or 4 side effects of second-line chemotherapy.

PMID:37909949 | DOI:10.21873/anticanres.16704

Anticancer Res. 2023 Nov;43(11):5253-5259. doi: 10.21873/anticanres.16727.

ABSTRACT

BACKGROUND/AIM: Everolimus (EVE)-based treatment is an option for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), but a predictive marker has not yet been established. The recommended dose of EVE in combination with endocrine therapy is 10 mg/day, but due to adverse effects, patients are frequently forced to reduce the dose. However, the correct maintenance dose to achieve a therapeutic effect is still under debate. Employing real-world data, we examined clinicopathological factors to predict the efficacy of EVE-based treatment, particularly focusing on daily dose intensity (DDI).

PATIENTS AND METHODS: Ninety-five patients with MBC who received EVE-based treatment in combination with exemestane during the period from 2014 to 2022 were retrospectively investigated. Doses of EVE were reduced as needed and DDI was calculated with total doses of EVE and the duration of the treatment.

RESULTS: Mean time-to-treatment-termination (TTT) was 25.4 weeks. Patients with tumors with a high Ki67 labeling index, low absolute lymphocyte count, and small DDI of EVE had significantly shorter TTT (p=0.006, 0.043, and 0.030, respectively). When patients were categorized based on DDI of EVE, patients with DDI ≤5 mg/day had significantly shorter TTT (p=0.002). There were no correlations between RDI and factors such as age, body weight, and numbers of previous treatments for MBC.

CONCLUSION: Maintaining a DDI of at least 5 mg/day seems crucial to achieving a therapeutic effect. Our data might be useful for determining the dosage of EVE in clinical practice.

PMID:37909948 | DOI:10.21873/anticanres.16727

Semin Oncol. 2023 Jul 31:S0093-7754(23)00059-3. doi: 10.1053/j.seminoncol.2023.07.001. Online ahead of print.

ABSTRACT

PURPOSE: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. We aim to identify the main barriers hindering clinical recommendations implementation and propose consensus solutions to improve OIC control in cancer patients.

METHODS: Following collaborative and prioritization techniques, a scientific committee generated statements addressing possible barriers to optimal OIC management (related to patients, health providers and health care system), and potential interventions to overcome these barriers. An expert panel of 36 oncologists assessed the statements to reach a consensus.

RESULTS: The survey consisted of 70 statements. Consensus was reached on 12/45 items related to barriers (26.6%) and on 19/25 items about corrective interventions (76%). The panel considered that patients are unaware of the existence of a specific OIC treatment, and their information sources are highly variable and unreliable. Regarding health providers, the panel considered that the oncologists prioritize symptoms such as diarrhea, pain, anxiety, or other treatment toxicities, over constipation. Work overload and bureaucratic requirements were the main barriers related to health care system. Regarding potential interventions, best-rated proposals included specific training programs development for primary care physicians and nurses, and multiplatform informative resources development for patients and caregivers, including precisely written instructions about OIC recognition and management. Oncologists assessed positively measures aiming to improve coordination between primary care physicians and oncologists, and nursing consultations implementation. The panel considered useful the OIC treatment algorithms simplification.

CONCLUSIONS: The expert panel identified the main barriers to optimal OIC management and suggested some feasible approaches to overcome these barriers.

PMID:37914616 | DOI:10.1053/j.seminoncol.2023.07.001

Paediatr Respir Rev. 2023 Sep 15:S1526-0542(23)00064-7. doi: 10.1016/j.prrv.2023.09.001. Online ahead of print.

ABSTRACT

Highly effective modulator therapies (HEMTs) have revolutionised the management approach of most patients living with cystic fibrosis (CF) who have access to these therapies. Clinical trials have reported significant improvements across multiorgan systems, with patients surviving longer. However, there are accumulating case reports and observational data describing various adverse events following initiation of HEMTs including drug-to-drug interactions, drug induced liver injury, Stevens-Johnson syndrome, and neurocognitive symptoms including psychosis and depression, which have required discontinuation of therapy. Current clinical trials are assessing efficacy in younger patients with CF, yet long-term studies are also required to better understand the safety profile in the real-world setting across all ages and the impact of HEMT dose alteration or discontinuation.

PMID:37914566 | DOI:10.1016/j.prrv.2023.09.001

BMC Gastroenterol. 2023 Oct 31;23(1):370. doi: 10.1186/s12876-023-03014-9.

ABSTRACT

BACKGROUND: Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.

METHODS: An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.

RESULTS: A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.

CONCLUSIONS: Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.

PMID:37907846 | DOI:10.1186/s12876-023-03014-9

In Vivo. 2023 Nov-Dec;37(6):2719-2725. doi: 10.21873/invivo.13382.

ABSTRACT

BACKGROUND/AIM: Torsade de pointes (TdP)/QT prolongation (QTP) is one of the most life-threatening adverse effects of antifungal triazoles. The aim of the present study was to evaluate the association of antifungal triazoles with TdP/QTP by age group and the profile of the time of TdP/QTP onset by analyzing the spontaneous adverse event database for Japan.

PATIENTS AND METHODS: Data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to March 2022 were analyzed. The association between the administration of antifungal triazoles and TdP/QTP according to age was evaluated using an adjusted reporting odds ratio (aROR). In addition, the time-to-onset of TdP/QTP after antifungal triazole treatment was analyzed using the Weibull distribution according to the route of administration.

RESULTS: Antifungal triazole treatment was associated with TdP/QTP (aROR=1.77, 95% confidence interval=1.52-2.07). In the subgroup analyses by age group, antifungal triazole treatments in patients ≤29 years old and ≥50 (except ≥90) years old were associated with TdP/QTP. The medians (quartiles) of time-to-onset for intravenous and oral antifungal triazole treatment were 8 (6-12) and 23 (8-86) days, respectively. In addition, the shape parameter in the Weibull distribution analysis of oral triazole treatment revealed that the hazard exhibited an early failure profile.

CONCLUSION: TdP/QTP is associated with antifungal triazoles even in young patients, and patients should be monitored for the development of TdP/QTP, especially early after the initiation of treatment.

PMID:37905641 | DOI:10.21873/invivo.13382

BMC Infect Dis. 2023 Oct 30;23(1):744. doi: 10.1186/s12879-023-08712-z.

ABSTRACT

Dolutegravir (DTG), an integrase strand transfer inhibitor is currently the recommended first and second line anti-retroviral therapy (ART) anchor agent by the World Health Organization due to its favorable side effect profile, high efficacy and genetic barrier to resistance.Despite its very good side effect profile, there have been multiple case reports of ART experienced patients developing hyperglycemia within weeks to a few months after switching to DTG preceded by weight loss. At population level, however, DTG as well as other integrase inhibitors have been demonstrated to have a reduced risk of incident diabetes mellitus (T2DM) compared to other HIV drug classes.Following multiple similar reports of accelerated hyperglycemia in Uganda during the first pilot year of DTG use, the Uganda Ministry of Health recommended withholding dolutegravir in all patients who develop diabetes. Whether this recommendation should be applied to all patients with incident T2DM remains to be demonstrated.We present a clinical case of an HIV positive ART naïve man who was diagnosed with T2DM after 36 weeks on DTG. We describe changes in blood glucose, glycated hemoglobin, insulin resistance and pancreatic beta cell function before and after withholding DTG. We demonstrated that he was phenotypically different from the reported cases of accelerated hyperglycemia and he continued to have worsening insulin resistance despite withholding DTG. His blood glucose improved with dietary T2DM management. It is possible he had an inherent risk of developing T2DM independent of his exposure to DTG. This put in question whether DTG should universally be withheld in PLHIV with incident T2DM in Uganda.

PMID:37904127 | PMC:PMC10617153 | DOI:10.1186/s12879-023-08712-z