Pathologie (Heidelb). 2022 Jul;43(4):256-262. doi: 10.1007/s00292-022-01082-4. Epub 2022 Jun 9.

ABSTRACT

Cytomorphological and histomorphological analysis of bone marrow cells in cases with abnormal production of blood cells must always take the unwanted side effects of drugs into account. Drugs can affect single lineages or the complete bone marrow. Besides quantitative phenomena consisting of hypoplasia or hyperplasia, maturation of blood cells may be disturbed. Disturbances encompass left shifts, which may be extreme, or imitate states of vitamin deficiency and atypia occurring in myelodysplastic syndromes (MDS). In addition, all bone marrow lineages may be affected, simulating aplastic anemia. The spectrum of causative drugs is very broad, and the induced changes are generally not specific enough to identify the underlying drug culprit, which requires knowledge of the patient's drug history. Cytotoxic drugs applied in oncology can induce MDS with an average latency of 2-6 years, or even shorter in the case of drugs interfering with DNA repair.

PMID:35925223 | DOI:10.1007/s00292-022-01082-4

JAMA. 2022 Aug 2;328(5):486. doi: 10.1001/jama.2022.8974.

NO ABSTRACT

PMID:35916845 | DOI:10.1001/jama.2022.8974

Pulm Pharmacol Ther. 2022 Jul 30:102144. doi: 10.1016/j.pupt.2022.102144. Online ahead of print.

ABSTRACT

BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH) combination therapy pooled sequential and initial combination together, which might threaten their authenticity and clinical significance for the difference between two strategies.

METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sequential combination therapy (SCT) with background therapy (BT) in PAH patients. Raw data were extracted to calculate risk ratio (RR) or weighted mean difference (WMD) for predefined efficacy and safety outcomes. Mantel-Haenszel fixed or random effects model was used based on heterogeneity.

RESULTS: 17 RCTs involving 4343 patients (97.2% of patients with WHO-FC II-III) were included. SCT decreased clinical worsening (RR 0.66, 95% CI 0.58 to 0.76), nonfatal clinical worsening (RR 0.61, 95% CI 0.52 to 0.71), functional class (decrease of 28% in the portion of patients with WHO-FC worsening and increase of 33% in the portion of patients with WHO-FC improvement), and increased 6-min walk distance (WMD 17.68 m, 95% CI 10.16 to 25.20), but didn't reduce mortality, lung transplantation, admission to hospital, and treatment escalation compared with BT. Although any adverse event and serious adverse event were similar between SCT and BT, SCT increased all-cause treatment discontinuation (RR 1.49, 95% CI 1.30 to 1.71) and drug-related treatment discontinuation (RR 2.30, 95% CI 1.86 to 2.84) with higher incidence of headache, flushing, nausea, diarrhoea and jaw pain.

CONCLUSIONS: For WHO-FC II-III PAH patients who have established BT, our study reinforced the recommendation of SCT to improve clinical worsening, functional status, and exercise capacity, although with higher incidence of side-effects and withdrawal.

PMID:35918025 | DOI:10.1016/j.pupt.2022.102144

Toxicol Lett. 2022 Aug 15;367:76-87. doi: 10.1016/j.toxlet.2022.07.814. Epub 2022 Jul 29.

ABSTRACT

Antipsychotic drugs represent a class of lysosomotropic drugs widely used in clinical practice. However, the hepatotoxicity of these drugs has been reported in recent years. Therefore, understanding the changes in cellular homeostasis mediated by these drugs is of great significance for revealing the true mechanisms underlying hepatotoxicity. Perphenazine is a classical antipsychotic drug that can reportedly induce extrapyramidal and sympatholytic side effects. The present research focuses on the toxicity effect of perphenazine on normal human hepatocytes. To assess the hepatotoxicity of continuous administration of perphenazine and investigate potential mechanisms related to apoptosis, human normal L02 hepatocytes were exposed to 10-40 μM perphenazine in vitro. The results showed that perphenazine inhibited cell viability in a concentration and time-dependent manner. Furthermore, 30 μM perphenazine induced intense lysosome vacuolation, impaired lysosomal membrane, and induced lysosomal membrane permeabilization (LMP), ultimately triggering lysosomal cell death in L02 cells. Knockdown cathepsin D(CTSD) also ameliorated perphenazine-induced liver injury via the inhibition of LMP. In vivo, ICR mice received intragastric administration of 10-180 mg/kg B.W. perphenazine every other day for 21 days. 180 mg/kg perphenazine significantly increased histological injury and aminotransferases compared with control. Taken together, our findings suggest that perphenazine can trigger hepatotoxicity through lysosome disruption both in vitro and in vivo.

PMID:35914675 | DOI:10.1016/j.toxlet.2022.07.814

Sci Rep. 2022 Aug 1;12(1):13189. doi: 10.1038/s41598-022-17410-w.

ABSTRACT

Tools to accurately predict and detect adverse drug reactions (ADR) in elderly patients have not been developed. We aimed to identify and evaluate reports on tools that predict and detect ADR in elderly patients (≥ 60 years). In this review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Databases were searched until January 2022 using key terms "elderly," "adverse drug reaction," and "detection instruments." Eighteen studies met the inclusion criteria, and they examined assorted interventions: STOPP/START version 1/2 (n = 10), Beers Criteria 2012 or 2015 (n = 4), Systematic Tool to Reduce Inappropriate Prescribing (STRIP) (n = 2), Tool to Reduce Inappropriate Medications (TRIM) (n = 1), Medication Risk Score (MERIS) (n = 1), Computerized alert systems (n = 1), and Norwegian General Practice-Nursing Home criteria (n = 1). The interventions affected the number of potential prescription omissions (OR, 0.50 [0.37-0.69]; p < 0.0001; four studies). No apparent reduction in the number of drug interactions within 2 months (OR, 0.84 [0.70-1.02]; p = 0.08; two studies) and mortality (OR, 0.92 [0.76-1.12]; p = 0.41; three studies) was observed. In conclusion, there is no definitive and validated assessment tool for detecting and predicting ADR in elderly patients. Thus, more research on refining existing tools or developing new ones is warranted.

PMID:35915219 | DOI:10.1038/s41598-022-17410-w

Cochrane Database Syst Rev. 2022 Aug 1;8(8):CD008295. doi: 10.1002/14651858.CD008295.pub6.

ABSTRACT

BACKGROUND: This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs.

OBJECTIVES: To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy.

SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 13 July 2021) on 15 July 2021. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.

SELECTION CRITERIA: We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, a third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life.

MAIN RESULTS: We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data. Only one study reported the outcome of 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate whilst another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants. We assessed the evidence for all outcomes using GRADE and rated the evidence as very low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update.

AUTHORS' CONCLUSIONS: In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.

PMID:35914010 | PMC:PMC9342851 | DOI:10.1002/14651858.CD008295.pub6

Chin J Integr Med. 2022 Aug 1. doi: 10.1007/s11655-022-3537-4. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC).

METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded.

RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug.

CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

PMID:35915317 | DOI:10.1007/s11655-022-3537-4

Cureus. 2022 Jul 26;14(7):e27307. doi: 10.7759/cureus.27307. eCollection 2022 Jul.

ABSTRACT

During the COVID-19 pandemic, there was an urgent need for any medication to help reduce the high death rate experienced during this deadly surge. Remdesivir is an FDA-approved drug for COVID-19 treatment, given its anti-inflammatory properties. Upon extensive literature search, we found two studies and four cases of COVID-19-induced pneumonia treated with remdesivir who were developing bradycardia. In most of these cases, the bradycardia resolved within one-to-two days of holding remdesivir, which correlated with the half-life of remdesivir. Remdesivir was shown to have benefits in COVID-19-induced pneumonia during the COVID-19 surge; however, its use has been controversial. According to the studies, the sinus bradycardia following remdesivir administration does not impact patients' prognosis in terms of ICU admission and in-hospital mortality. There are multiple case reports noted to report several remdesivir-induced cardiac side effects. In our case, prolonged use and high dosages may induce cardiotoxicity, manifesting as severe bradycardia. Several possible mechanisms for cardiac adverse effects with remdesivir need further investigation and research as COVID-19 remains an active global issue. We present a 53-year-old man hospitalized with COVID-19-induced pneumonia who experienced extreme sinus bradycardia that is likely attributable to remdesivir.

PMID:35910702 | PMC:PMC9329595 | DOI:10.7759/cureus.27307

Pain Ther. 2022 Jul 31. doi: 10.1007/s40122-022-00417-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), formerly also called baboon syndrome, is characterized by symmetrical erythematous rash with typical localization in the gluteal and intertriginous areas. A type IV delayed hypersensitivity immune response is thought to be responsible for its development. CGRP monoclonal antibodies (CGRP mAbs) are a new class of drugs for the prevention of migraine. We present the first case of SDRIFE occurring in temporal relation to the use of erenumab for migraine prevention.

CASE: A 48-year-old female patient with migraine received erenumab 140 mg subcutaneously in the thigh area for the prevention of migraine in repetitive cycles, each 1 month apart. Initially, the patient experienced no side effects. After the third cycle, a masseuse incidentally noticed a reddish, circular rash in the buttock area during a back massage. There were no other symptoms. The skin changes resolved spontaneously. Two years later, approximately 40 h after reapplication of erenumab 140 mg, the patient experienced a severe pain in the buttock area centered over the anal crease. The area of pain extended in a circular pattern with approximately 20 cm in diameter. The pain started abruptly and reached a severe intensity within about 30 min. Sitting on the buttocks was no longer possible for the patient. There was marked allodynia and hyperpathia in the entire buttocks region. A flat, broad-based blister-like skin swelling developed in this region. The blisters began opening up on the fourth day after the onset of the skin reaction. In addition, there was a pronounced redness in the entire buttock area. Here, the patient felt a strong burning pain, similar to a scald.

RESULTS: The symptoms lasted for a period of 10 days. From this point on, they fully subsided under concomitant therapy with prednisolone.

CONCLUSION: SDRIFE as a rare dermatological side effect should be considered in the monitoring of skin lesions during migraine prophylaxis. In view of the high migraine prevalence, knowledge of this uncommon syndrome is important. It is crucial to recognize the relationship between the medication and the circumscribed exanthema occurring distant from the injection site.

PMID:35908264 | DOI:10.1007/s40122-022-00417-6

PLoS One. 2022 Jul 29;17(7):e0271587. doi: 10.1371/journal.pone.0271587. eCollection 2022.

ABSTRACT

The timely reporting of adverse drug reactions (ADRs) could improve pharmacovigilance (PV) in a healthcare system. However, in almost all healthcare systems barriers exist that lead to the underreporting of ADRs. The objective of this study was to identify the barriers and facilitators regarding PV activities from the point of view of healthcare professionals (HCPs) in Lahore, Pakistan. A cross-sectional questionnaire-based survey was conducted between September 2018 to January 2019. The data was collected through convenience sampling of physicians, pharmacists, and nurses at tertiary care public hospitals in Lahore. A total of 384 questionnaires were distributed, and 346 HCPs responded to the survey. Over 62% percent of physicians and 54.8% of nurses agreed that they did not know how to report an ADR in their workplace. About 43.2% of pharmacists and 40.1% of nurses disagreed that they were not aware of the need for ADR reporting. Furthermore, 41.6% of nurses identified a lack of financial reimbursement and 51.8% highlighted a lack of support from a colleague as a reason that could lead to the underreporting of ADR. The majority of participants, including 69.6% physicians, 48.6% pharmacists, and 55.3% nurses identified the lack of knowledge about the existence of a national PV centre. Extra time for ADR reporting, incentives, continuous medical education, reminders, and availability of an online ADR reporting system was classed as the facilitators and were agreed upon by the majority of HCPs.

PMID:35905133 | PMC:PMC9337632 | DOI:10.1371/journal.pone.0271587

Pediatr Emerg Care. 2022 Aug 1;38(8):399-403. doi: 10.1097/PEC.0000000000002793.

ABSTRACT

E-cigarettes, or electronic cigarettes, are electronic nicotine delivery systems that are marketed as a healthier alternative to tobacco cigarettes. There has been an exponential increase in their use among youth since their introduction to the United States market in 2007. With increased use and popularity, there has been an increase in calls to poison control centers regarding liquid nicotine toxicity in children and adolescents. Recent US Food and Drug Administration and other federal regulations of e-cigarettes have attempted to limit availability to youth. This article reviews trends in e-cigarette use among youth, the background and mechanism of action of e-cigarettes, liquid nicotine toxicity, management of liquid nicotine toxicity, and recent policy updates regarding e-cigarettes.

PMID:35904953 | DOI:10.1097/PEC.0000000000002793

Clin Interv Aging. 2022 Jul 21;17:1127-1138. doi: 10.2147/CIA.S368871. eCollection 2022.

ABSTRACT

PURPOSE: Geriatric inpatients generally have a high risk of drug-related problems (DRP) in prescribing following hospital admission, which are likely to cause negative clinical consequences. This is particularly evident in developing countries such as Vietnam. Therefore, clinical pharmacy service (CPS) aims to identify and resolve these DRPs to improve the quality use of medicines in the older population following hospital admission.

PATIENTS AND METHODS: The study was conducted as a prospective, single-center study implemented at a general public hospital in Hanoi. Patients aged ≥60 years with at least three chronic diseases admitted to the Internal Medicine Department between August 2020 and December 2020 were eligible to be enrolled. A well-trained clinical pharmacist provided a structured CPS to identify any DRP in prescribing for each patient in the study. Clinical pharmacist interventions were then proposed to the attending physicians and documented in the DRP reporting system.

RESULTS: A total of 255 DRP were identified in 185 patients during the study period. The most frequent types of DRP were underuse (21.2%), dose too high (12.2%), and contraindication (11.8%). There was a very high rate of approval and uptake by the physicians regarding the interventions proposed by the clinical pharmacist (82.4% fully accepted and 12.5% partially accepted). Of the interventions, 73.4% were clinically relevant (pADE score ≥0.1). In general, 9 out of 10 physicians agreed that CPS has significant benefits for both patients and physicians.

CONCLUSION: Improving clinical pharmacy services can potentially have a positive impact on the quality of prescribing in elderly inpatients. These services should officially be implemented to optimize the quality use of medicines in this population group in Vietnam.

PMID:35903286 | PMC:PMC9314755 | DOI:10.2147/CIA.S368871

Therapie. 2022 Jul 16:S0040-5957(22)00121-4. doi: 10.1016/j.therap.2022.07.004. Online ahead of print.

NO ABSTRACT

PMID:35906144 | DOI:10.1016/j.therap.2022.07.004

Drug Ther Bull. 2022 Jul 29:dtb-2022-000041. doi: 10.1136/dtb.2022.000041. Online ahead of print.

ABSTRACT

Overview of: Tucker KL, Mort S, Yu LM, et al Effect of self-monitoring of blood pressure on diagnosis of hypertension during higher-risk pregnancy: the BUMP 1 randomized clinical trial. JAMA 2022;327:1656-65; and Chappell LC, Tucker KL, Galal U, et al Effect of self-monitoring of blood pressure on blood pressure control in pregnant individuals with chronic or gestational hypertension: the BUMP 2 randomized clinical trial. JAMA 2022;327:1666-78.

PMID:35906004 | DOI:10.1136/dtb.2022.000041

Lancet HIV. 2022 Aug;9(8):e534-e543. doi: 10.1016/S2352-3018(22)00173-4.

ABSTRACT

BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants.

METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181.

FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life.

INTERPRETATION: Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing.

FUNDING: Unitaid.

PMID:35905752 | DOI:10.1016/S2352-3018(22)00173-4

Saudi Pharm J. 2022 Jul;30(7):1052-1059. doi: 10.1016/j.jsps.2022.04.006. Epub 2022 Apr 19.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are undesired, unintended responses to drugs, and are significantly underreported. Pharmacists are drug experts recognized as custodians of drug safety, who are expected to be prepared for and knowledgeable about ADR reporting.

OBJECTIVES: To identify Egyptian community pharmacists' preparedness for and perceived barriers to spontaneous ADR reporting.

METHODS: This cross-sectional study recruited a sample of community pharmacists across Egypt, who were invited to complete a self-administrated questionnaire during April 2020.

RESULTS: A total of 923 pharmacists across Egypt responded to the questionnaire. Most pharmacists were knowledgeable about the definition of ADRs (93.9 %) and indicated they felt reporting ADRs benefits the patients (82.2%). Despite recognizing their public health value, only a small percentage of participants conveyed familiarity with the reporting process for both paper (19.2%) and electronic (30.4%) forms, indeed 56.6% of participants did not remember what the ADR report form looked like. Moreover, 75.4% of respondents said they felt that community pharmacies are not the right place for reporting, with 49% suggesting that reporting was the responsibility of physicians. However, only 32.1% reported having insufficient time being a barrier to ADR reporting.

CONCLUSIONS: Community pharmacists in Egypt are not well prepared for spontaneous ADR reporting due to a lack of knowledge about the formal process and not acknowledging their responsibility, although time was not a major barrier. Therefore, this highlights a clear opportunity for improvement likely involving targeted education.

PMID:35903525 | PMC:PMC9315256 | DOI:10.1016/j.jsps.2022.04.006

Respir Res. 2022 Jul 28;23(1):192. doi: 10.1186/s12931-022-02112-8.

ABSTRACT

BACKGROUND: Inhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor's clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors.

METHODS: First, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region.

RESULTS: EMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA.

CONCLUSION: Behaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.

PMID:35902927 | PMC:PMC9330944 | DOI:10.1186/s12931-022-02112-8

PLoS One. 2022 Jul 28;17(7):e0271260. doi: 10.1371/journal.pone.0271260. eCollection 2022.

ABSTRACT

In numerous classification problems, class distribution is not balanced. For example, positive examples are rare in the fields of disease diagnosis and credit card fraud detection. General machine learning methods are known to be suboptimal for such imbalanced classification. One popular solution is to balance training data by oversampling the underrepresented (or undersampling the overrepresented) classes before applying machine learning algorithms. However, despite its popularity, the effectiveness of sampling has not been rigorously and comprehensively evaluated. This study assessed combinations of seven sampling methods and eight machine learning classifiers (56 varieties in total) using 31 datasets with varying degrees of imbalance. We used the areas under the precision-recall curve (AUPRC) and receiver operating characteristics curve (AUROC) as the performance measures. The AUPRC is known to be more informative for imbalanced classification than the AUROC. We observed that sampling significantly changed the performance of the classifier (paired t-tests P < 0.05) only for few cases (12.2% in AUPRC and 10.0% in AUROC). Surprisingly, sampling was more likely to reduce rather than improve the classification performance. Moreover, the adverse effects of sampling were more pronounced in AUPRC than in AUROC. Among the sampling methods, undersampling performed worse than others. Also, sampling was more effective for improving linear classifiers. Most importantly, we did not need sampling to obtain the optimal classifier for most of the 31 datasets. In addition, we found two interesting examples in which sampling significantly reduced AUPRC while significantly improving AUROC (paired t-tests P < 0.05). In conclusion, the applicability of sampling is limited because it could be ineffective or even harmful. Furthermore, the choice of the performance measure is crucial for decision making. Our results provide valuable insights into the effect and characteristics of sampling for imbalanced classification.

PMID:35901023 | PMC:PMC9333262 | DOI:10.1371/journal.pone.0271260

Biomed Res Int. 2022 Jul 18;2022:8742998. doi: 10.1155/2022/8742998. eCollection 2022.

ABSTRACT

Background: Drug therapy in the elderly needs an emphasis on age-related changes in drug pharmacokinetics and pharmacodynamics profile. Hospitalized elderly patients are at risk of more than one disease and polypharmacy associated with these; they are at risk of drug-related problems. This study aimed to assess the role of clinical pharmacy on identifying and resolution of drug-related problems among elderly patients admitted to medical ward of Northwest Ethiopia comprehensive specialized hospitals. Methods: A multicenter prospective observational study was conducted. A systematic sampling technique was used. The identified drug-related problem was recorded and classified using Cipolle, and adverse drug reaction was assessed using Naranjo algorithm of adverse drug reaction probability scale, and Medscape was used for drug-drug interaction. Data were analyzed by using STATA software version 14.1. Logistic regression was used, and results were reported as odds ratios (ORs) with 95% Confidence intervals with P value < 0.05 statistically significant. Result: A total of 389 study participants were included in the study. About 266 (68.4%) of the participants had at least a single drug-related problem. About 503 drug-related problems were identified with a mean of 1.32 (CI: 1.27-1.36) drug-related problem per patient. The three-leading categories of drug-related problems were dose too high 108 (21.5%), nonadherence 105 (20.9%), and adverse drug reaction 96 (19.1%). Alcohol use (AOR = 2.2, 95CI%: 1.23-3.94), source of the drug (AOR = 2.85, 95CI%: 1.63-4.98), length of hospitalization (AOR = 2.32, 95CI%: 1.37-3.95), number of comorbidities (AOR = 1.48, 95CI%: 1.09-1.99), and polypharmacy (AOR = 3.06, 95CI%: 1.72-5.46) were important risk factors for drug-related problems. From the intervention provided, 84.7% were accepted by prescribers. Among the total drug-related problems 67.4% of the problem was totally solved. Conclusion: This study revealed that DRPs were high among elderly patients admitted to medical ward of Northwest Ethiopia. Comorbidity, length of hospitalization, ploy-pharmacy, payer, and alcohol drinker were more likely to developed drug-related problems. Treatment optimizations were also done by clinical pharmacists and interventions were well accepted by prescribers.

PMID:35898673 | PMC:PMC9314180 | DOI:10.1155/2022/8742998

Drug Ther Bull. 2022 Jul 28:dtb-2022-000038. doi: 10.1136/dtb.2022.000038. Online ahead of print.

NO ABSTRACT

PMID:35902110 | DOI:10.1136/dtb.2022.000038