Drug-induced Adverse Events

Deep learning in drug discovery: an integrative review and future challenges
Artif Intell Rev. 2022 Nov 17:1-63. doi: 10.1007/s10462-022-10306-1. Online ahead of print.
ABSTRACT
Recently, using artificial intelligence (AI) in drug discovery has received much attention since it significantly shortens the time and cost of developing new drugs. Deep learning (DL)-based approaches are increasingly being used in all stages of drug development as DL technology advances, and drug-related data grows. Therefore, this paper presents a systematic Literature review (SLR) that integrates the recent DL technologies and applications in drug discovery Including, drug-target interactions (DTIs), drug-drug similarity interactions (DDIs), drug sensitivity and responsiveness, and drug-side effect predictions. We present a review of more than 300 articles between 2000 and 2022. The benchmark data sets, the databases, and the evaluation measures are also presented. In addition, this paper provides an overview of how explainable AI (XAI) supports drug discovery problems. The drug dosing optimization and success stories are discussed as well. Finally, digital twining (DT) and open issues are suggested as future research challenges for drug discovery problems. Challenges to be addressed, future research directions are identified, and an extensive bibliography is also included.
PMID:36415536 | PMC:PMC9669545 | DOI:10.1007/s10462-022-10306-1
Intravenous acetaminophen associated with acute liver failure
BMJ Case Rep. 2022 Nov 22;15(11):e251305. doi: 10.1136/bcr-2022-251305.
ABSTRACT
A woman in her mid-60s, without known liver disease, was admitted to the hospital with a partial malignant colonic obstruction. Over a 6-day course, she received a total of 13 g of intravenous acetaminophen not exceeding 4 g over a 24-hour period. She developed encephalopathy and an international normalised ratio of 6.1 meeting criteria for acute liver failure (ALF). She was treated with intravenous N-acetyl cysteine and other causes of liver failure were excluded. The patient was discharged with subsequent resolution of encephalopathy and improvement of her liver chemistries. Though ALF is rare, in countries where acetaminophen is readily available, almost 50% of ALF cases are acetaminophen-induced hepatotoxicity and most have been documented as oral ingestion of acetaminophen. We present a rare case of intravenous acetaminophen-induced ALF.
PMID:36414340 | DOI:10.1136/bcr-2022-251305
A Nursing Educational Intervention to Improve Antiestrogen Adherence and Self-Management of Side Effects
Clin J Oncol Nurs. 2022 Nov 18;26(6):606-611. doi: 10.1188/22.CJON.606-611.
ABSTRACT
Antiestrogens prescribed to reduce breast cancer risk or recurrence can have undesirable musculoskeletal side effects that may lead to early discontinuation of therapy. Previous studies have not focused on nurse-led assessmen.
PMID:36413725 | DOI:10.1188/22.CJON.606-611
Phenytoin as treatment for bidirectional ventricular tachycardia in a patient with anterior myocardial infarction and digoxin toxicity
Arch Cardiol Mex. 2022;92(4):550-552. doi: 10.24875/ACM.21000262.
NO ABSTRACT
PMID:36413700 | DOI:10.24875/ACM.21000262
Change of genitourinary cancer patients' perception and expectations over the course of pharmacotherapy
PLoS One. 2022 Nov 22;17(11):e0278039. doi: 10.1371/journal.pone.0278039. eCollection 2022.
ABSTRACT
To determine the course of treatment while considering the patients' desires, we examined trends regarding patients' perception and expectations over the course of cancer pharmacotherapy. We retrospectively reviewed interview sheets filled in by patients with advanced urogenital cancers when they started a new pharmacotherapy regimen between 2014 and 2020. The responses to the following questions were analyzed: 1) How did your doctor explain the treatment objectives?; 2) Are you willing to receive treatment?; and 3) When the standard treatment becomes difficult to continue, would you like to try another treatment even if it may cause severe side effects? A total of 277 patients answered the interview sheet. The percentage of patients who accurately perceived the treatment objectives among patients receiving 1st, 2nd, and 3rd line regimens was 67%, 79%, and 93%, respectively. The percentage significantly improved over the course of pharmacotherapy (p = 0.0057). The percentage of patients who indicated that they were willing to receive treatment in 1st, 2nd, and 3rd line regimens was 80%, 83%, and 86%, respectively. The percentage of patients who indicated that they wanted to try another treatment when the standard treatment became difficult to continue in 1st, 2nd, and 3rd line regimens was 56%, 64%, and 59%, respectively. The percentage of patients who accurately perceived the objective of pharmacotherapy increased over the course of pharmacotherapy. The rate of patients who were willing to receive treatment and try other treatments when the standard treatment became too difficult to continue remained consistently high.
PMID:36413565 | DOI:10.1371/journal.pone.0278039
Development and assessment of the Quality of Life Instruments for Chronic Diseases-Gout (QLICD-GO) (V2.0)
Clin Rheumatol. 2022 Nov 22. doi: 10.1007/s10067-022-06440-4. Online ahead of print.
ABSTRACT
OBJECTIVE: To develop and assess the Quality of Life Instruments for Chronic Diseases-Gout QLICD-GO (V2.0).
METHODS: The instrument was developed using a programmatic decision-making method to combine the general module of the Quality of Life Instruments for Chronic Diseases and a new specific module. The instrument was assessed by measuring the quality of life of 116 patients with gout.
RESULTS: The QLICD-GO (V2.0) included 28 items from the general module of chronic diseases and 12 items in three facets from the specific module. In addition to the field of physiological function, the internal consistency reliability of other fields and dimensions of the instrument was > 0.7, and the split-half reliability was > 0.5. Three common factors were extracted from the specific module, with a cumulative variance contribution rate of 57.54%. The standardized response means of the specific module and the whole instrument were 0.94 and 1.20, respectively.
CONCLUSIONS: The QLICD-GO (V2.0) has good reliability, validity, and responsiveness. The instrument comprehensively and objectively reflects the quality of life of patients with gout, and it can be used to assess treatment regimens developed by medical staff. Key Points • The QLICD-GO (V2.0) has been developed for patients with gout based upon the foundation of the QLICD-GM. • The QLICD-GO reflects the clinical signs and symptoms, drug-related side effects, and psychological changes specific to patients with gout. • Based on the assessment results, the QLICD-GO (V2.0) has good reliability, validity, and responsiveness. • QLICD-GO (V2.0) can objectively and comprehensively reflect the QOL of patients with gout and can be used by clinical staff to assess treatment regimens.
PMID:36414865 | DOI:10.1007/s10067-022-06440-4
Case of hepatotoxicity of atorvastatin: the search for a possible etiology
Tijdschr Gerontol Geriatr. 2022 May 30;53(3). doi: 10.36613/tgg.1875-6832/2022.03.03. eCollection 2022 May 30.
ABSTRACT
We describe a case of a geriatric patient with repeated hepatotoxicity after (re)start of atorvastatin. We also noticed an increased effect, a fast decline of LDL-cholesterol, after intake of atorvastatin. The intake of rosuvastatin or low dose lovastatin was not associated with hepatotoxicity. Multiple hypotheses were investigated and applied on the case. Genetic testing of statin transporters and CYP-enzymes and medication interactions could not explain the hepatotoxicity.
PMID:36408752 | DOI:10.36613/tgg.1875-6832/2022.03.03
Opioid-related adverse drug reactions in patients visiting the emergency division of a tertiary hospital
Pharmacol Res Perspect. 2022 Dec;10(6):e01033. doi: 10.1002/prp2.1033.
ABSTRACT
Opioid use and associated morbidity and mortality have increased in several countries during the past 20 years. We performed a study whose objective was to assess the frequency and causes of opioid-related emergency division (ED) visits in an adult tertiary Swiss University Hospital over 9 weeks in 2018. We primarily assessed opioid-related adverse drug reactions (ADR), secondary overdose, misuse, abuse, and insufficient pain relief. Current opioid use was identified in 1037 (8.3%) of the 12 470 included ED visits. In 64 opioid users, an ADR was identified as a contributing cause of the ED visit, representing 6.2% of opioid users, and 0.5% of the total ED visits. Moreover, we identified an overdose in 16 opioid users, misuse or abuse in 19 opioid users, and compatible withdrawal symptoms in 7 opioid users. After pooling all these events, we conclude that the ED visits could be related to opioid use in 10.2% of opioid users. Finally, in 201 opioid users, insufficient pain relief (pain not responding to the current pharmacological treatment) was identified as a contributing cause of ED visits. In these cases, other factors than simply pharmacological nonresponse may have been involved. In the context of an ever-increasing opioid use to better control chronic pain situations, these results should reinforce emergency network epidemiological surveillance studies at a national level.
PMID:36404650 | DOI:10.1002/prp2.1033
A retrospective evaluation of side-effects associated with the booster dose of Pfizer-BioNTech/BNT162b2 COVID-19 vaccine among females in Eastern Province, Saudi Arabia
Vaccine. 2022 Nov 22;40(49):7087-7096. doi: 10.1016/j.vaccine.2022.10.009. Epub 2022 Oct 17.
ABSTRACT
BACKGROUNDS: The development of several types of vaccines to avert COVID-19 has taken place. Despite several reports of undesirable reactions noted post-COVID-19 vaccine administration, later remains one of the best prevention and management tools in fighting the spread of the virus and its variants and reducing the harshness of this viral attack. The purpose of the current paper was to explore the side-effects experienced by the females in the Eastern Province of Saudi Arabia directly after receiving the booster dose of the Pfizer-BioNTech/BNT162b2 COVID-19 vaccine.
METHODS: A descriptive cross-sectional study among adults living in the East-ern Province, Saudi Arabia was applied. A survey link was, distributed through WhatsApp, SMS, or e-mail to community members. Respondent's demographic information was acquired, as well as information about any local and systemic side-effects reported following booster dose of BioNTech/BNT162b2 COVID-19 vaccine.
RESULTS: A total of 72.36% (432/597) of the respondents who participated in this study reported at least one side-effect. Pain and redness at the injection site (75.93%), myalgia (71.99%), headache (53.24%), fever (33.56%), and fatigue (43.78%) were the highest frequently stated side-effects. Furthermore, 9.25% of the respondents had to see a physician due to side effects, plus merely four participants were admitted to the hospital. The respondents working in the non-healthcare-related sector had a 1.677-fold more possibility of side effects in comparison with the other respondents (adjusted odds ratio = 1.677; 95% CI = 1.363, 2.064).
CONCLUSIONS: All reported side-effects were mild to moderate. These findings might persuade pessimists and refusers to get the COVID-19 vaccine. Myalgia and pain or redness at the site of injection were the most common reported side-effects in our study.
PMID:36404426 | DOI:10.1016/j.vaccine.2022.10.009
Low dose vancomycin-loaded spacers for two-stage revision knee arthroplasty: High success, low toxicity
Knee. 2022 Nov 18;40:63-70. doi: 10.1016/j.knee.2022.11.008. Online ahead of print.
ABSTRACT
BACKGROUND: Two-stage revision arthroplasty is a widely used treatment method for infected knee arthroplasty. Loading high doses of antibiotics to spacer during the first stage is standard practice. However, there are reported systemic side effects attributed to antibiotic-loaded spacers. The aim of our study is to investigate the success rate and systemic toxicity following the first stage revision knee arthroplasty with low-dose vancomycin-loaded spacers.
METHOD: We included patients with infected knee arthroplasty eligible for two-stage revision arthroplasty from 2001 to 2020. One gram of vancomycin is added per pack of bone cement. Spacers were handmade in the operating theatre. Following the first stage, pre-operative and postoperative culture results, infection parameters, kidney and liver function tests, and functional scores were analyzed. Kaplan-Meier survival analysis was done to determine the success rate.
RESULTS: Fifty patients with a mean follow-up of 48 months (24-108) were included in the study. A five-year survival analysis showed an 88.5% success rate. Fourteen percent of the patients had acute kidney injury with creatinine levels between 1.12-2.80 mg/dl, and 8% had a mild drug-induced liver injury with elevated serum ALT levels between 223-540 U/L and total bilirubin levels between 0.59-1.23 mg/dl. None of the patients required dialysis. All of the systemic side effects were reversible.
CONCLUSION: Our results have suggested that low dose antibiotic-loaded spacers are comparable to the studies with high dose antibiotic loaded spacers regarding infection eradication and survival rates. They are less likely to cause severe systemic side effects. Therefore we suggest low dose antibiotic-loaded spacers should be considered when treating patients with vancomycin sensitive Staphylococcal species and culture negative infected knee arthroplasty.
PMID:36410252 | DOI:10.1016/j.knee.2022.11.008
Immune checkpoint inhibitor (ICI)-induced hepatitis diagnosed by liver biopsy followed by ICI-free chemotherapy leading to therapeutic effect: A case of lung cancer treatment
Respir Med Case Rep. 2022 Nov 8;40:101773. doi: 10.1016/j.rmcr.2022.101773. eCollection 2022.
ABSTRACT
In recent years, the combination of platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) has become the standard treatment for patients with lung cancer. Hepatitis is one of the common toxicities following ICI/chemotherapy. When drug-induced hepatitis occurs, the suspected drug must be discontinued. Since it may be difficult to determine the exact drug causing the hepatitis, liver biopsy may help identify this. We report the case of a patient diagnosed with immune-related adverse event hepatitis from liver biopsy and clinical course. A 45-year-old man with lung adenocarcinoma (stage IV, cT4N3M1c) negative for driver gene mutation was treated with carboplatin (CBDCA), pemetrexed (PEM), and pembrolizumab. Elevated blood aspartate aminotransferase and alanine aminotransferase levels after chemotherapy indicated hepatitis induced by cytotoxic anticancer agents and ICIs. As autoimmune hepatitis was also suspected, liver biopsy was performed and the findings suggested ICI-induced hepatitis. Pembrolizumab was discontinued and CBDCA/PEM was resumed, following which, the primary lesion shrank. When drug-induced hepatitis is suspected, clinicians should actively perform liver biopsy to confirm the diagnosis, so that appropriate therapeutic regimen can be administered.
PMID:36408484 | PMC:PMC9672405 | DOI:10.1016/j.rmcr.2022.101773
Prevalence of Physical and Psychological Impacts of Wearing Personal Protective Equipment on Health Care Workers During COVID-19: A Systematic Review and Meta-Analysis
Indian J Occup Environ Med. 2022 Jul-Sep;26(3):140-150. doi: 10.4103/ijoem.ijoem_32_22. Epub 2022 Sep 26.
ABSTRACT
BACKGROUND: The COVID-19 pandemic has necessitated the use of personal protective equipment (PPE) among the frontline health care workers (HCWs). Even though PPE helps in preventing infection, it poses significant physical and psychological impacts at varying levels. Correspondingly, multiple independent studies have brought out the PPE-associated problems. However, there exists a lacuna on comprehensive information of global prevalence related to the same.
AIM: To estimate the prevalence and risk factors of PPE among HCWs during COVID-19 across the globe.
DESIGN: Systematic review and meta-analysis.
METHOD: The review was undertaken as per the protocol registered in PROSPERO CRD42021272216 following Preferred Reporting Items for Systematic Reviews and Meta-Analysis(PRISMA) guidelines. Two independent reviewers have undertaken the search strategy, study selection, and methodological quality assessment. Discrepancies were addressed by the third reviewer. Heterogeneity was addressed through I2 statistics and forest plots generated by open meta-software.
RESULTS: A total of 16 articles conducted across 6 different countries among 10,182 HCWs were included in the review. The pooled prevalence of skin lesions, headache, sweating, breathing difficulty, vision difficulty, thirst/dry mouth, fatigue, and communication difficulty, anxiety, fear were 57 (47-66%), 51 (37-64%), 75 (56-90%), 44 (23-68%), 61 (21-94%), 54 (30-77%), 67 (58-76%), 74 (47-94%), 28 (24-33%), 14 (10-17%), respectively. Moreover, the various risk factors included are the use of PPE for >6 h and young females. In addition, the medical management of new-onset problems created an additional burden on the frontline health care personnel (HCP).
CONCLUSION: The frontline HCWs encountered physical and psychological problems at varying levels as a result of wearing PPE which needs to be addressed to prevent the inadequate use of PPE leading to infections.
PMID:36408432 | PMC:PMC9674076 | DOI:10.4103/ijoem.ijoem_32_22
A Case of Ecstasy-Induced Acute Hepatic Injury
Cureus. 2022 Oct 17;14(10):e30377. doi: 10.7759/cureus.30377. eCollection 2022 Oct.
ABSTRACT
The recreational use of a drug such as 3,4-methylenedioxymethamphetamine (MDMA), also known as "ecstasy," may be associated with significant side effects. Although liver failure with ecstasy is rare, the use of the drug should be investigated in all patients with severe hepatitis of unknown origin. Early diagnosis and intervention can prevent patients from ending up in liver transplantation. Here, we present a case of a 27-year-old female who developed acute liver injury secondary to recreational intoxication with ecstasy.
PMID:36407170 | PMC:PMC9671195 | DOI:10.7759/cureus.30377
Low-dose febuxostat exhibits a superior renal-protective effect and non-inferior safety profile compared to allopurinol in chronic kidney disease patients complicated with hyperuricemia: A double-centre, randomized, controlled study
J Clin Pharm Ther. 2022 Nov 20. doi: 10.1111/jcpt.13794. Online ahead of print.
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: The present study compared the efficacy and safety of low-dose febuxostat versus allopurinol in chronic kidney disease (CKD) patients complicated with hyperuricemia (HUA).
METHODS: In this double-centre, randomized, controlled study, 120 CKD patients complicated with HUA were recruited and randomly assigned to low-dose febuxostat group (20 mg/day) or allopurinol group (200 mg/day) at 1:1 ratio. The serum creatinine (Scr), serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were measured at baseline (M0), month (M) 1, M3, and M6. Besides, the drug-related adverse events (AEs) were recorded. The primary outcome was the proportion of patients showing a > 10% decline in eGFR from M0 to M6.
RESULTS: The eGFR level was increased at M6, but similar at M0, M1 and M3 in febuxostat group compared with allopurinol group. Notably, the proportion of patients with >10% decline in eGFR from M0 to M6 was decreased in febuxostat group compared with allopurinol group. However, there was no difference of Scr, SUA at M0, M1, M3 and M6 between febuxostat group and allopurinol group. Moreover, there was no difference of drug-related AEs between febuxostat group and allopurinol group. Further subgroup analysis exhibited that low-dose febuxostat presented superior effect on attenuating eGFR decline and lowering SUA level compared with allopurinol in CKD stage 3 subgroup, but not in CKD stage 2 subgroup.
CONCLUSION: Low-dose febuxostat may exhibit a superior renal-protective effect, non-inferior SUA lowering ability and safety profile compared with allopurinol in CKD patients complicated with HUA.
PMID:36403976 | DOI:10.1111/jcpt.13794
Efficacy, residual effectiveness and safety of diacerein in the treatment of knee osteoarthritis: A meta-analysis of randomized placebo-controlled trials
Medicine (Baltimore). 2022 Nov 18;101(46):e31700. doi: 10.1097/MD.0000000000031700.
ABSTRACT
BACKGROUND: Osteoarthritis (OA) is the leading cause of disability in the elderly. Prevention and treatment of OA have become an urgent global demand. The pharmacologic role of diacerein in the treatment of osteoarthritis is controversial. We systematically reviewed the efficacy, safety, and residual effectiveness of diacerein.
OBJECTIVES: To estimate the symptomatic efficacy, residual effect and safety of diacerein in the treatment of knee osteoarthritis, using a meta-analysis of published randomized controlled trials (RCTs).
METHODS: On December 1, 2021, we searched PubMed Medline, Web of Science, Cochrane Library databases, Wan Fang Medical Database, and National Knowledge Infrastructure. This study followed the inclusion criteria of the principle P(Population), I(Intervention), C(Comparison), O(Outcome), S (Study design) principle. All studies were randomized controlled trials of knee osteoarthritis. Cochrane bias risk assessment tool was used to assess the risk of bias. Meta-analyses were performed using a random-effects model. To explore sources of heterogeneity, subgroup analysis, sensitivity analysis, regression analysis and publication bias analysis were performed. Drug side effects with complete data were extracted from the included articles and then a combined analysis of these data was performed.
RESULTS: Eight studies were eligible and were included in our analysis (N = 1277 participants). All studies were randomized controlled trials of knee osteoarthritis. There was no significant difference in reduction of joint pain and improvement of function between diacerein and the control group. However, subgroup analysis suggested, compared with the placebo group, diacerein treatment yielded an improved mean reduction in visual analogue scale score of-0.44% (95% confidence interval [CI]-0.79 to 0.09), an improved the western Ontario and McMaster universities (physical function) score of -0.44% (95% CI-0.72 to -0.12). Follow-up analysis after discontinuation showed that diacerein treatment had a significant residual effect (95% CI-0.81 to- 0.24). Data on drug side effects described in the included articles were extracted for statistical analysis. There was an increased risk of diarrhea with diacerein (Risk Ratio [RR] = 1.95 [1.03 to 2.47]) and withdrawal event from therapy (RR = 0.93 [0.75 to 1.15]).
CONCLUSION: Diacerein might be considered an effective drug for the treatment of patients with KOA, showing short-term residual effectiveness. Although it is associated with an increased risk of diarrhea, the adverse event is mostly tolerable.
PMID:36401382 | DOI:10.1097/MD.0000000000031700
The status of TKI/acid-suppressant concomitant use in 44 hospitals in China: A cross-sectional descriptive study
Medicine (Baltimore). 2022 Nov 18;101(46):e31770. doi: 10.1097/MD.0000000000031770.
ABSTRACT
The irrational use of tyrosine kinase inhibitors (TKIs) has attracted increasing attention, especially because of drug-drug interactions. The objective of this study was to analyze TKI prescriptions and evaluate the rationality of concomitant use of TKIs and acid-suppressants. TKI prescriptions from 2016 to 2018 were collected from hospitals in Beijing, Guangzhou, Hangzhou, and Zhengzhou for 40 d/yr. Focusing on the data in 2018, we analyzed the pharmacoeconomic indicators of TKIs and the number and proportion of different coprescriptions. The evaluation criteria for coprescriptions were based on clinical literature and package inserts. A total of 41,738 TKI prescriptions were assessed. The total dose and sales of imatinib were the highest, the medication days and defined daily doses of gefitinib were the highest, and the highest defined daily cost was sunitinib. Meanwhile, there were 17 TKIs with drug utilization indices of ≤ 1.0. The irrational combination rate of prescriptions of non-cancer-related departments was high in 3 cities, but not Hangzhou. The irrational combination rate of prescription of inpatient prescriptions was > 23% in the 4 cities. The combined use of TKIs and acid-suppressants is common in China and may have a clear or potential impact on the pharmacokinetics, pharmacodynamics, and adverse drug reactions of TKIs. Therefore, it is urgent to implement necessary interventions to stop such irrational use or if the combined use is necessary, to correct adverse consequences. The aims should be to achieve safe and effective use of TKIs and reduce unnecessary costs.
PMID:36401366 | DOI:10.1097/MD.0000000000031770
Spatial-temporal trends in the risk of illicit drug toxicity death in British Columbia
BMC Public Health. 2022 Nov 18;22(1):2121. doi: 10.1186/s12889-022-14586-8.
ABSTRACT
BACKGROUND: Illicit drug poisoning (overdose) continues to be an important public health problem with overdose-related deaths currently recorded at an unprecedented level. Understanding the geographic variations in fatal overdose mortality is necessary to avoid disproportionate risk resulting from service access inequity.
METHODS: We estimated the odds of fatal overdose per event from all cases captured by the overdose surveillance system in British Columbia (2015 - 2018), using both conventional logistic regression and Generalized Additive Models (GAM). The results of GAM were mapped to identify spatial-temporal trends in the risk of fatal overdose.
RESULTS: We found that the odds of fatal overdose were about 30% higher in rural areas than in large urban centers, with some regions reporting odds 50% higher than others. Temporal variations in fatal overdose revealed an increasing trend over the entire province. However, the increase occurred earlier and faster in the Interior and Northern regions.
CONCLUSION: Rural areas were disproportionately affected by fatal overdose; lack of access to harm reduction services may partly explain the elevated risk in these areas.
PMID:36401244 | PMC:PMC9675064 | DOI:10.1186/s12889-022-14586-8
The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study
BMC Health Serv Res. 2022 Nov 17;22(1):1363. doi: 10.1186/s12913-022-08696-7.
ABSTRACT
BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit.
METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group.
RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039).
CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.
PMID:36397102 | PMC:PMC9670389 | DOI:10.1186/s12913-022-08696-7
Drug resistant tuberculosis among elderly: Challenges
Indian J Tuberc. 2022;69 Suppl 2:S202-S204. doi: 10.1016/j.ijtb.2022.10.022. Epub 2022 Oct 26.
ABSTRACT
The article deals with challenges faced by the geriatric populations while on MDR treatment. Risk factors like tobacco use, low socio-economic status, previous disease, longer delays in seeking treatment and reduced mobility are some of the challenges while initiating MDR treatment. Other issues like drug-related adverse events and increased co-morbidity pose a major challenge while treating patients. Susceptibility among the geriatric age group includes various anatomical and physiological changes including nutritional deficiencies and co morbidities.
PMID:36400509 | DOI:10.1016/j.ijtb.2022.10.022
Cost-effectiveness of single, high-dose, liposomal amphotericin regimen for HIV-associated cryptococcal meningitis in five countries in sub-Saharan Africa: an economic analysis of the AMBITION-cm trial
Lancet Glob Health. 2022 Dec;10(12):e1845-e1854. doi: 10.1016/S2214-109X(22)00450-8.
ABSTRACT
BACKGROUND: HIV-associated cryptococcal meningitis is a leading cause of AIDS-related mortality. The AMBITION-cm trial showed that a regimen based on a single high dose of liposomal amphotericin B deoxycholate (AmBisome group) was non-inferior to the WHO-recommended treatment of seven daily doses of amphotericin B deoxycholate (control group) and was associated with fewer adverse events. We present a five-country cost-effectiveness analysis.
METHODS: The AMBITION-cm trial enrolled patients with HIV-associated cryptococcal meningitis from eight hospitals in Botswana, Malawi, South Africa, Uganda, and Zimbabwe. Taking a health service perspective, we collected country-specific unit costs and individual resource-use data per participant over the 10-week trial period, calculating mean cost per participant by group, mean cost-difference between groups, and incremental cost-effectiveness ratio per life-year saved. Non-parametric bootstrapping and scenarios analyses were performed including hypothetical real-world resource use. The trial registration number is ISRCTN72509687, and the trial has been completed.
FINDINGS: The AMBITION-cm trial enrolled 844 participants, and 814 were included in the intention-to-treat analysis (327 from Uganda, 225 from Malawi, 107 from South Africa, 84 from Botswana, and 71 from Zimbabwe) with 407 in each group, between Jan 31, 2018, and Feb 17, 2021. Using Malawi as a representative example, mean total costs per participant were US$1369 (95% CI 1314-1424) in the AmBisome group and $1237 (1181-1293) in the control group. The incremental cost-effectiveness ratio was $128 (59-257) per life-year saved. Excluding study protocol-driven cost, using a real-world toxicity monitoring schedule, the cost per life-year saved reduced to $80 (15-275). Changes in the duration of the hospital stay and antifungal medication cost showed the greatest effect in sensitivity analyses. Results were similar across countries, with the cost per life-year saved in the real-world scenario ranging from $71 in Botswana to $121 in Uganda.
INTERPRETATION: The AmBisome regimen was cost-effective at a low incremental cost-effectiveness ratio. The regimen might be even less costly and potentially cost-saving in real-world implementation given the lower drug-related toxicity and the potential for shorter hospital stays.
FUNDING: European Developing Countries Clinical Trials Partnership, Swedish International Development Cooperation Agency, Wellcome Trust and Medical Research Council, UKAID Joint Global Health Trials, and the National Institute for Health Research.
TRANSLATIONS: For the Chichewa, Isixhosa, Luganda, Setswana and Shona translations of the abstract see Supplementary Materials section.
PMID:36400090 | DOI:10.1016/S2214-109X(22)00450-8