PLoS One. 2023 Apr 14;18(4):e0284439. doi: 10.1371/journal.pone.0284439. eCollection 2023.

ABSTRACT

BACKGROUND: Drug therapy problems (DTPs) are common among patients suffering from chronic kidney disease (CKD). However, there is a lack of information about DTPs and its predictors among CKD patients from Pakistan.

OBJECTIVES: To evaluate the frequency, type and predictors of various types of DTPs among CKD patients at a tertiary-care hospital in Pakistan.

METHODOLOGY: This was a cross-sectional study carried out at Sandeman Provincial Hospital, Quetta between 1-11-2020 and 31-1-2021. It included 303 non-dialysis ambulatory patients of CKD-stage 3 and above. Cipolle et al., criterion was used for classifying the DTPs and a clinician at the study site checked the identified DTPs for accuracy. Data were analyzed by SPSS 23. Multivariate analysis was conducted to find the predictors of individual types of DTPs. A p-value <0.05 was considered statistically significant.

RESULTS: The patients received a total of 2265 drugs with a median of eight drugs per patient (range: 3-15 drugs). A total of 576 DTPs were identified among 86.1% patients with a median of two DTPs (interquartile range 1-3) per patient. Dosage too high (53.5%) was the most common DTP followed by adverse drug reactions (ADRs) (50.5%) and need of additional drug therapy (37.6%). In multivariate analysis, patients' age of >40 years emerged as a predictor of unnecessary drug therapy and dosage too high. The odds of needing a different drug product was significantly high in patients with cardiovascular diseases (CVD) and diabetes mellitus (DM). The dosage too low had significant association with CVD. The risk of ADRs was significantly high in elderly patients (>60 years) and those with CVD. The presence of hypertension, DM and CKD stage-5 emerged as predictors of dosage too high.

CONCLUSION: This study revealed a high prevalence of DTPs among CKD patients. Targeted interventions in high risk patients may reduce the frequency of DTPs at the study site.

PMID:37058504 | PMC:PMC10104314 | DOI:10.1371/journal.pone.0284439

Anal Cell Pathol (Amst). 2023 Apr 4;2023:1714884. doi: 10.1155/2023/1714884. eCollection 2023.

ABSTRACT

Acetaminophen has always been at the center of attention as a non-steroidal anti-inflammatory drug, which is generally associated with the serious side effects on liver and the hematological parameters. This study aimed to compare the effect of N-acetyl cysteine (NAC) and thyme extract on rat models of acetaminophen-induced toxicity. The present experimental study was conducted on 48 Wistar rats randomized into six groups, including the control group (no treatment); the Ac group (470 mg/kg of acetaminophen); the Ac + 100Ex, Ac + 200Ex, and Ac + 400Ex groups (acetaminophen + thyme extract at doses of 100, 200, 400 mg/kg); and Ac + NA group (acetaminophen + NAC). After weighing, a blood sample was taken from heart at the end of the period. The measured parameters were hematological, liver biochemical, and oxidative stress profiles. A part of the liver tissue was also fixed for the pathological examinations. The bone marrow was aspirated to check for cellular changes as well. The lowest mean of the final weight and liver weight to body weight ratio was observed in the Ac group. Weight loss was compensated in Ac + NA and Ac + 200Ex groups (P = 0.035). White blood cell (WBC), red blood cell (RBC), Hemoglobin (Hgb), and Hematocrit (HCT) in Ac and Ac + 400Ex groups showed significant differences from those of the other test groups (P < 0.001). Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) enzymes in Ac + 200Ex and Ac + NA groups showed a significant decrease compared to those of the other treatment groups (P = 0.043). Total antioxidant capacity (TAC) and glutathione peroxidase (GPx) had the lowest levels in Ac and Ac + 400Ex groups, while malondialdehyde (MDA) had the highest content. In this regard, the liver histopathological indices (necrosis, hyperemia, and hemorrhage) in the Ac + 200Ex and Ac + NA groups reached their lowest grades in the treatment groups. The mean number of erythroid and myeloid cells in the Ac group reached the lowest (17.40 ± 3.48). The microscopic appearance of the bone marrow cells was different from normocytosis in the control group to hypocytosis in the Ac and Ac + 400Ex groups. Thymol, as an effective ingredient in thyme extract at a dose of 200 mg/kg compared to NAC, had a unique effect on reducing bone marrow and liver cell-tissue changes due to the acetaminophen toxicity.

PMID:37056637 | PMC:PMC10089780 | DOI:10.1155/2023/1714884

Ecotoxicol Environ Saf. 2023 May;256:114874. doi: 10.1016/j.ecoenv.2023.114874. Epub 2023 Apr 11.

ABSTRACT

Lead (Pb), cadmium (Cd) and total mercury (THg) are toxic heavy metals (THMs) that are widely present in the environment and can cause substantial health problems. However, previous risk assessment studies have rarely focused on the elderly population and have usually targeted a single heavy metal, which might underestimate the long-term accumulative and synergistic effects of THMs in humans. Based on the food frequency questionnaire and inductively coupled plasma mass spectrometry, this study assessed external and internal exposures to Pb, Cd and THg in 1747 elderly people in Shanghai. Probabilistic risk assessment with the relative potential factor (RPF) model was used to assess the neurotoxicity and nephrotoxicity risks of combined THMs exposures. The mean external exposures of Pb, Cd and THg in Shanghai elderly were 46.8, 27.2 and 4.9 μg/day, respectively. Plant-based foods are the main source of Pb and THg exposure, while Cd is mainly from animal-based foods. The mean concentrations of Pb, Cd and THg were 23.3, 1.1 and 2.3 μg/L in the whole blood, and 6.2, 1.0 and 2.0 μg/L in the morning urine, respectively. Combined exposure to THMs leading to 10.0 % and 7.1 % of Shanghai elderly at risk of neurotoxicity and nephrotoxicity. The results of this study have important implications for understanding the profiles of Pb, Cd and THg exposure in the elderly living in Shanghai and provide data support for risk assessment and control of nephrotoxicity and neurotoxicity from combined THMs exposure in the elderly.

PMID:37054469 | DOI:10.1016/j.ecoenv.2023.114874

PLoS One. 2023 Apr 13;18(4):e0281395. doi: 10.1371/journal.pone.0281395. eCollection 2023.

ABSTRACT

BACKGROUND AND AIMS: Vaccination is the most powerful public health intervention proven to be safe and effective in the battle against the coronavirus disease-2019 (COVID-19) pandemic. Despite the potential therapeutic benefits of primer vaccine dosage regimens, public perceptions of COVID-19 vaccine booster dose (VBD) acceptance and hesitancy vary among various sub-group populations. This study investigates COVID-19 vaccine booster dose acceptance and compares the multi-dimensional potential factors influencing VBD acceptance and hesitancy among university teachers and the student community in Bangladesh.

METHODS: This web-based cross-sectional study employed an anonymous, validated, and self-administered questionnaire. The questionnaire items were adopted from a theoretical analysis of the recent relevant literature. The questionnaire was deployed in an on-line-enabled format (Google form) and conveniently distributed to 685 teachers and 990 students between 15th June, 2022 and 15th August, 2022 which resulted in the participation of 1250 (505 teachers vs.745 students) total respondents (response rate 73.72% vs. 75.25%) from various universities in Bangladesh. A non-parametric analytical tool (binary logistic regression) was applied to rationalize the study objectives and a Chi-squared test was performed to estimate the booster- hesitant risky group.

RESULTS: The pooled COVID-19 vaccine booster dose acceptance rates were 84.6% (95% CI 81.5─87.7) and 67.2% (95% CI 63.8─70.6) for teachers and students in the university academic community, respectively. In employing a binary logistic regression, this study revealed that out of twelve (12)multi-dimensional key predictors, "equal safety", "risk-benefit ratio", and "variant control" had a significant positive association with VBD acceptance in both sets (p = 0.000, p = 0.000, and p = 0.005, respectively). Varied effects were found for several predictors; post-vaccination "side effects" had a significant negative association (p = 0.020) and "community protection" had significant positive association (p = 0.034) with vaccine booster dose acceptance in the teachers community while these variables were insignificant in the students cohort. "Trust" had a highly significant positive association (p = 0.000);"communication" and "academic attainment" had significant positive associations (p = 0.033 and 0.024, respectively) with VBD acceptance in the students cohort, while these predictors were insignificant in the teachers community. Women were more likely to receive a third dose of the vaccine (OR = 1.4 vs. 0.9 between teacher and student model); however, no significant association between gender and booster vaccine acceptance was found in a comparative Chi-squared model. Therefore, statistically, the booster vaccine-hesitant risky group was not found to implicate the massive booster vaccine drive among the university academic community.

CONCLUSIONS: COVID-19 booster vaccine acceptability among the student cohort was slightly lower than pre-roll-out intent. The teacher community was more inclined to get booster vaccinated. Moreover, differences were found between the multi-dimensional potential factors associated with VBD acceptance among teachers and students in university settings. This study explicitly confirmed positive attitudes toward the safety, health benefits, and variants control of the COVID-19 VBD under any circumstances. Post-vaccination side effect concern was found to be a barrier to administering booster shots and a reason for booster skepticism. Tailored communication and health education interventions need to be adopted to improve the public awareness of booster vaccine consequences, and limit booster skepticism.

PMID:37053270 | PMC:PMC10101431 | DOI:10.1371/journal.pone.0281395

Molecules. 2023 Mar 28;28(7):3004. doi: 10.3390/molecules28073004.

ABSTRACT

Anthracycline doxorubicin (DOX) is still widely used as a chemotherapeutic drug for some solid tumors. Although DOX is highly effective, its side effects are limiting factors, such as cardio, nephro and hepatotoxicity. As such, approaches used to mitigate these adverse effects are highly encouraged. Omega 3 (ω-3), which is a class of long-chain polyunsaturated fatty acids, has been shown to have anti-inflammatory and antioxidant effects in preclinical bioassays. Thus, we evaluated the protective effects of ω-3 supplementation on hepatotoxicity and nephrotoxicity induced by multiple DOX administrations in rodents. Male Wistar rats (10 rats/group) were treated daily with ω-3 (400 mg/kg/day) by gavage for six weeks. Two weeks after the first ω-3 administration, the rats received DOX (3.5 mg/kg, intraperitoneal, 1×/week) for four weeks. DOX treatment reduced body weight gain increased systemic genotoxicity and caused liver-related (increase in serum ALT levels, thickness of the Glisson's capsule, compensatory proliferation and p65 levels) and kidney-related (increase in serum urea and creatinine levels, and incidence of tubular dilatation) deleterious outcomes. In contrast, ω-3 supplementation was safe and abrogated the DOX-related enhancement of systemic genotoxicity, serum urea and creatinine levels. Furthermore, ω-3 intervention reduced by 50% the incidence of kidney histological lesions while reducing by 40-50% the p65 protein level, and the proliferative response in the liver induced by DOX. Our findings indicate that ω-3 intervention attenuated the DOX-induced deleterious effects in the liver and kidney. Therefore, our findings may inspire future mechanistical investigations and clinical interventions with ω-3 on the reported outcomes.

PMID:37049766 | DOI:10.3390/molecules28073004

Nutrients. 2023 Mar 28;15(7):1635. doi: 10.3390/nu15071635.

ABSTRACT

Ensuring optimal iodine nutrition in pregnant women is a global public health concern. However, there is no direct data on safe tolerable upper intake levels (ULs) for pregnant women. A cross-sectional study was performed to determine the ULs of pregnant women. A total of 744 pregnant women were enrolled in this study. The median (IQR) urinary iodine concentration (UIC) in pregnant women was 150.2 (87.6, 268.0) μg/L, and the urinary iodine excretion (UIE) over 24 h was 204.2 (116.0, 387.0) μg/day. Compared with those with a UIE figure of between 150-250 μg/day, the reference group, the prevalence of thyroid dysfunction was 5.7 times higher (95%CI: 1.7, 19.2) in pregnant women with a UIE figure of between 450-550 μg/day, and 3.9 times higher (95%CI: 1.5, 10.3) in pregnant women with a UIE figure of ≥550 μg/day. Compared with an estimated iodine intake (EII) of between 100-200 μg/day, the reference group, the prevalence of thyroid dysfunction was 4.3 times higher (95%CI: 1.3, 14.4) in pregnant women with a UIE figure of between 500-600 μg/day, and 3.6 times higher (95%CI: 1.5, 8.9) in pregnant women with UIE of ≥600 μg/day. In general, our cross-sectional study found that excessive iodine intake during pregnancy appears to directly increase the risk of thyroid dysfunction. Avoiding chronic iodine intakes of 500 μg/day or higher or having a UIE figure of ≥450 μg/day is recommended for pregnant women in China.

PMID:37049475 | DOI:10.3390/nu15071635

Int J Mol Sci. 2023 Apr 5;24(7):6771. doi: 10.3390/ijms24076771.

ABSTRACT

In pharmaceutical treatment, many non-cardiac drugs carry the risk of prolonging the QT interval, which can lead to fatal cardiac complications such as torsades de points (TdP). Although the unexpected blockade of ion channels has been widely considered to be one of the main reasons for affecting the repolarization phase of the cardiac action potential and leading to QT interval prolongation, the lack of knowledge regarding chemical structures in drugs that may induce the prolongation of the QT interval remains a barrier to further understanding the underlying mechanism and developing an effective prediction strategy. In this study, we thoroughly investigated the differences in chemical structures between QT-prolonging drugs and drugs with no drug-induced QT prolongation (DIQT) concerns, based on the Drug-Induced QT Prolongation Atlas (DIQTA) dataset. Three categories of structural alerts (SAs), namely amines, ethers, and aromatic compounds, appeared in large quantities in QT-prolonging drugs, but rarely in drugs with no DIQT concerns, indicating a close association between SAs and the risk of DIQT. Moreover, using the molecular descriptors associated with these three categories of SAs as features, the structure-activity relationship (SAR) model for predicting the high risk of inducing QT interval prolongation of marketed drugs achieved recall rates of 72.5% and 80.0% for the DIQTA dataset and the FDA Adverse Event Reporting System (FAERS) dataset, respectively. Our findings may promote a better understanding of the mechanism of DIQT and facilitate research on cardiac adverse drug reactions in drug development.

PMID:37047744 | DOI:10.3390/ijms24076771

Allergol Int. 2023 Apr 11:S1323-8930(23)00037-0. doi: 10.1016/j.alit.2023.03.006. Online ahead of print.

ABSTRACT

BACKGROUND: The epidemiology of drug-induced anaphylaxis using the Japanese nationwide database has been not reported, even though drugs are a common trigger of anaphylaxis. The aim of this study was to describe the epidemiological profile of cases of drug-induced anaphylaxis, including fatal cases, using the data from the Japanese Adverse Drug Event Report database (JADER).

METHODS: We extracted data regarding drug-related adverse events, between April 2004 and February 2018, published in JADER by the Pharmaceuticals and Medical Devices Agency. We analyzed cases of anaphylaxis occurring between January 2005 and December 2017. The drug classification was based on the Japanese Standard Commodity Classification.

RESULTS: There were 16,916 cases of anaphylaxis reported during the study period. Among them, 418 fatalities were registered. The incidence of drug-induced anaphylaxis and fatal cases was 1.03 cases/year per 100,000 population and 0.03 cases/year, respectively. The most frequent causes of anaphylaxis were diagnostic agents, including X-ray contrast media (20.3%), and biological preparations, such as human blood preparations (20.1%). In fatal cases, diagnostic agents (28.7%) and antibiotic preparations (23.9%) were the most commonly associated types of drugs.

CONCLUSIONS: The frequency of drug-induced anaphylaxis and fatalities in Japan remained unchanged over the 13-year period analyzed in this study. Diagnostic agents and biological preparations were the most frequent causes of anaphylaxis; however, fatalities were most frequently caused by either diagnostic agents or antibiotic preparations.

PMID:37055270 | DOI:10.1016/j.alit.2023.03.006

Int Urogynecol J. 2023 Apr 13. doi: 10.1007/s00192-023-05528-y. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The goal of this meta-analysis was to determine the efficacy and safety of medication for treating overactive bladder (OAB) in patients with Parkinson's disease (PD).

METHODS: Papers containing predefined key terms were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases up to December 2021 to collect randomized double-blind placebo-controlled trials (RCTs). The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Two reviewers independently assessed the risk of bias using the modified Jadad scale and Cochrane risk-of-bias tool. The GRADEpro GDT was employed to evaluate the strength of evidence based on the findings of this meta-analysis.

RESULTS: We eventually included four RCTs involving 313 patients (163 patients in the medication group and 150 patients in the placebo group). Of these, the therapeutic agent in two RCTs was mirabegron (121 and 106 patients and controls, respectively, representing 3/4 -2/3 of the patients). The results showed that the number of micturition episodes per 24 h (MD -1.33; 95% CI -2.30 to -0.36; p = 0.007), the number of nocturia episodes per 24 h (MD -0.33; 95% CI -0.58 to -0.08; p = 0.009) and the number of urinary incontinence episodes per 24 h (MD -0.72; 95% CI -1.32 to -0.12; p = 0.02) were significantly lower in the medication group than in the placebo group. The OAB symptom score (MD -2.84; 95% CI -4.67 to -1.00; p = 0.002) and quality of life score (MD 15.15; 95% CI 12.33 to 17.96; p < 0.0001) of the medication group were significantly improved compared with those of the placebo group. However, no significant difference in the daily frequency of urinary urgency episodes was identified between the medication group and the placebo group (MD -0.79; 95% CI -1.71 to 0.14; p = 0.09). There were no significant differences between the two groups in terms of drug-related adverse events (OR 1.69; 95% CI 0.41 to 6.99; p = 0.47), especially in PD patients receiving mirabegron therapy.

CONCLUSIONS: Medication was effective for OAB symptoms in patients with PD, and patients tolerated adverse events well.

PMID:37052644 | DOI:10.1007/s00192-023-05528-y

Trials. 2023 Apr 12;24(1):268. doi: 10.1186/s13063-023-07137-y.

ABSTRACT

BACKGROUND: The prevalence of colorectal cancer (CRC) worldwide is a huge challenge to human health. Primary tumor locations found to impact prognosis and response to therapy. The important role of gut microbiota in the progression and treatment of CRC has led to many attempts of alleviating chemotherapy-induced adverse effects using microecologics. However, the underlying mechanism of the difference in the prognosis of different primary tumor locations and the synergistic effect of prebiotics on chemotherapy need to be further elucidated. This study aims to explore the differences in tumor microbiota and examine the effectiveness of xylooligosaccharides (XOS) on gut microbiota, adverse effects, and bioavailability of chemotherapy drugs in CRC patients at different primary tumor locations.

METHODS: This is a double-blinded, randomized, parallel controlled clinical trial. Participants with left-sided CRC (LSCRC, n = 50) and right-sided CC (RSCC, n = 50) will randomly allocated to prebiotic group (n = 25) or control group (n = 25) and will receive either a daily XOS (3 g/day) or placebo, respectively, for 12 weeks. The primary outcomes will be the differences in the mucosa microbiota composition at different tumor locations and differences in gut microbiota composition, adverse effects, and blood concentration of capecitabine posttreatment. The secondary outcomes will include other blood indicators, short-chain fatty acids (SCFAs) concentration, quality of life, and mental health.

DISCUSSION: This study will reveal the potential benefits of prebiotic for improving the gut microbiota composition, alleviating the adverse effects, and improving the efficacy of chemotherapy in patients with CRC. In addition, this study will provide data on the different distribution of tumor microbiota and the different changes of gut microbiota during treatment in LSCRC and RSCC, which may provide novel insights into personalized cancer treatment strategies based on primary tumor locations and gut microbiota in the future.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ( www.chictr.org.cn ): ChiCTR2100046237. Registered on 12 May 2021.

PMID:37046334 | DOI:10.1186/s13063-023-07137-y

Clin Geriatr Med. 2023 May;39(2):273-293. doi: 10.1016/j.cger.2023.01.008.

ABSTRACT

Over the next several decades, rates of aged populations will increase rapidly. These populations are susceptible to multimorbidities and polypharmacy (concurrently, prescribed 5 or more medications). Many medications have side effects that manifest orally. Therefore, it essential to possess current pharmacologic knowledge to diagnose and treat oral implications of commonly prescribed medications. This article details common medication-induced oral lesions and patient assessment of risk factors for polypharmacy and provides a template to integrate medication reconciliation into dental clinical practice.

PMID:37045533 | DOI:10.1016/j.cger.2023.01.008

J Eur Acad Dermatol Venereol. 2023 Apr 12. doi: 10.1111/jdv.19112. Online ahead of print.

ABSTRACT

BACKGROUND: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation.

METHODS: We aim to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into 4 categories: inflammatory dermatosis, bullous diseases, drug-related eruptions and pigmentary diseases.

RESULTS: Inflammatory benign dermatoses (n=63) represented the most common group of reactions (52.5%), followed by drug-related eruptions (n=24, 20%), pigmentary diseases (n=23, 19.2%), and bullous diseases (n=10, 8.3%). Grade II (n=41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculo-papular rash, pruritus, psoriasis-like rash, urticarial eruption and vitiligo. Grade III (n=18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption, and rashes. Grade IV (n=2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n=95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time-to-onset of 208 days and some late-onset events.

CONCLUSION: Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I-II cutaneous IrAE are easily managed allowing ongoing anti-cancer treatment. Severe late-onset cutaneous irAE are not uncommon. A dermatologic follow-up helps mitigate the risk of life-threatening adverse events. These findings highlight the importance of onco-dermatologic involvement in management of patients with melanoma receiving immunotherapy.

PMID:37042810 | DOI:10.1111/jdv.19112

Drugs Aging. 2023 Apr;40(4):369-376. doi: 10.1007/s40266-023-01021-9. Epub 2023 Apr 11.

ABSTRACT

BACKGROUND: Polypharmacy in older people is steadily increasing and a combination of many medicines may result in adverse effects, especially if the medicines interact pharmacodynamically. Examples are additive or synergistic effects increasing the risk of falls, haemorrhage, serotonin syndrome and torsade de pointes. The clinical decision support system Janusmed Risk Profile has been developed to find such risks based on a patients' medication list.

OBJECTIVES: The main aim of this retrospective register-based study was to study what pharmacodynamic risks older patients (aged 65 years or older) on polypharmacy (defined as using five or more medicines) are exposed to. Second, we studied if the introduction of the Janusmed Risk Profile in the main electronic health record system in Region Stockholm influenced the proportion of patients prescribed combinations that increase the risk for the nine adverse-effect categories defined (anticholinergic effects, haemorrhage, constipation, orthostatism, QT prolongation, renal toxicity, sedation, seizures and serotonin syndrome).

METHODS: Data on all prescription medicines to individuals aged 65 years or older, and with at least five concomitant medicines were retrieved and analysed for the risk categories in the Janusmed Risk Profile. The proportions of patients with a high/moderate risk during a 4-month period before (period 1) and after (period 2) the introduction were compared.

RESULTS: A total of 127,719 patients in period 1 (November 2016-February 2017), and 131,458 patients in period 2 (November 2017-February 2018) were included in the study. The proportion of patients with a high or moderate risk for each of the nine properties (anticholinergic effects, haemorrhage, constipation, orthostatism, QT prolongation, renal toxicity, sedation, seizures and serotonergic effects) were 10.9, 34.7, 32.8, 33.6, 17.2, 0.7, 15.4, 0.5 and 2.4%, respectively, in period 1 and 10.4, 35.5, 32.8, 33.3, 10.8, 0.71, 14.9, 0.5 and 2.3% in period 2. The changes for sedation and QT prolongation were statistically significant, with the most pronounced decrease for QT prolongation from 17.2 to 10.8% (p < 0.001). When analysing patients at a high risk, the decrease was significant for haemorrhage, orthostatism, QT prolongation and sedation.

CONCLUSIONS: Older people are exposed to combinations of medications that increase the risk for potentially severe adverse effects. Prescribers seem to respond especially to warnings for QT prolongation, presented in the Janusmed Risk Profile implemented in the electronic health record system.

PMID:37039960 | PMC:PMC10113338 | DOI:10.1007/s40266-023-01021-9

Dermatol Online J. 2023 Feb 15;29(1). doi: 10.5070/D329160217.

ABSTRACT

Cutaneous side-effects of varenicline, a selective partial agonist of the a4B2 nicotinic acetylcholine receptor used to treat smoking addiction, are relatively rare and mainly consist of acute generalized exanthematous pustulosis. We describe an atypical clinical presentation of a varenicline-induced drug eruption, which occurred one day after drug initiation. We report this case since we believe no drug reaction to varenicline has had this clinical presentation or rapidity of onset. Clinicians should be aware of this potential adverse cutaneous reaction in patients taking varenicline for smoking cessation.

PMID:37040914 | DOI:10.5070/D329160217

Dermatol Online J. 2023 Feb 15;29(1). doi: 10.5070/D329160211.

ABSTRACT

Pretibial myxedema, more generally thyroid dermopathy, results from mucopolysaccharide accumulation in the dermis, typically between the knee and dorsal foot. Thyroid dermopathy presents in Graves disease, but can occur in Hashimoto thyroiditis, primary hypothyroidism, and euthyroid patients. Treatment of thyroid eye disease with teprotumumab is established in the literature, with few case reports also showing improvement in pretibial myxedema. Reported is a 76-year-old man with thyroid eye disease and pretibial myxedema treated with teprotumumab; improvement was demonstrated in both conditions. He developed "muffled" hearing as an adverse effect, a complication not widely published in the dermatology literature. At 18 months post-treatment, his symptoms are stable without recurrence, but hypoacusis persists. Given the long-term efficacy and side-effects, dermatologists should recognize the potential benefits and risks of using teprotumumab for thyroid dermopathy. A baseline audiogram may be considered prior to therapy. Additionally, longitudinal data is needed to document the benefits and risks of this novel therapy.

PMID:37040908 | DOI:10.5070/D329160211

Dermatol Online J. 2023 Feb 15;29(1). doi: 10.5070/D329160209.

ABSTRACT

Nirmatrelvir-ritonivir (Paxlovid) recently received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19). Literature has linked numerous cutaneous adverse effects to nirmatrelvir and ritonavir, the copackaged tablets within Paxlovid. A review and comparison of these adverse effects to the common cutaneous manifestations of COVID-19 is provided. Numerous drug-to-drug interactions exist between nirmatrelvir-ritonivir and commonly-used medications within dermatology.

PMID:37040906 | DOI:10.5070/D329160209

Indian J Med Res. 2023 Jan;157(1):30-36. doi: 10.4103/ijmr.IJMR_1273_19.

ABSTRACT

BACKGROUND & OBJECTIVES: The information available regarding delayed adverse donor reactions (D-ADRs) is limited. Proactive follow up of donors for delayed reactions is not done routinely. This study was undertaken to analyze frequency and type of D-ADRs in whole blood donors as also the contributory factors.

METHODS: In this prospective observational study, all eligible whole blood donors were contacted telephonically twice (24 h and 2 wks after donation) and asked about general health and ADR specific questions. The International Society of Blood Transfusion standard guidelines were used to categorize ADRs.

RESULTS: The ADR data of 3514 donors were analyzed in the study. D-ADRs were more common as compared to immediate delayed adverse donor reactions (I-ADRs) (13.7 vs. 2.9%, P<0.001). The most common D-ADRs were bruises (4.98%), fatigue or generalized weakness (4.24%) and sore arms (2.25%). D-ADRs were more common in first time donors as compared to the repeat blood donors (16.1 vs. 12.5%, P=0.002). Females were more prone to D-ADRs (17 vs. 13.6%). Localized D-ADRs were more frequent as compared to systemic D-ADRs (P<0.001). Repeat donors had a lower incidence of systemic D-ADRs (4.11% vs. 7.37%, P<0.001).

INTERPRETATION & CONCLUSIONS: D-ADRs were more common than I-ADRs with a different profile. First time, female and young donors were more prone to D-ADRs. These categories need special care at the time of blood donation. Active follow up of blood donors should be done from time to time to strengthen donor safety.

PMID:37040224 | DOI:10.4103/ijmr.IJMR_1273_19

Drug Ther Bull. 2023 Apr 11:dtb-2023-000019. doi: 10.1136/dtb.2023.000019. Online ahead of print.

ABSTRACT

Overview of: Medicines and Healthcare products Regulatory Agency. Pholcodine-containing cough and cold medicines: withdrawal from UK market as a precautionary measure. Drug Safety Update 2023;16:1.

PMID:37041073 | DOI:10.1136/dtb.2023.000019

Infect Drug Resist. 2023 Apr 4;16:2019-2028. doi: 10.2147/IDR.S404855. eCollection 2023.

ABSTRACT

PURPOSE: To assess the impact of targeted antibiotic therapy on clinical outcomes of patients with lower respiratory tract (LRT) infection with Corynebacterium striatum (C. striatum).

METHODS: A new propensity score-inverse probability of treatment weighting (IPTW) cohort study was conducted by using 10-year data. The study included LRT infection patients with respiratory secretions cultured positive for C. striatum simultaneously. The primary outcome was all-cause hospital mortality; the secondary outcomes included hospital stay, ICU stay and ventilation time. The safety outcomes were drug-related serum creatinine (Cr) increase and thrombocytopenia.

RESULTS: A total of 339 patients were included in the cohort, and 84 (24.78%) initiated vancomycin or linezolid therapy. In the new IPTW cohort, targeted antibiotic therapy did not improve all-cause hospital mortality (P=0.632), and the OR (95% CI) was 0.879 (0.519-1.488). Moreover, targeted antibiotic therapy was not associated with hospital stay (P=0.415), ICU stay (P=0.945) or ventilation time (P=0.885). The side effects of drug-related higher serum Cr (P=0.044) and thrombocytopenic levels (P=0.038) cannot be ignored.

CONCLUSION: Clinical benefits by vancomycin or linezolid targeted against LRT infection with C. striatum were limited and with drug-related side effects. A prospectively designed study is needed to further confirm the results.

PMID:37038476 | PMC:PMC10082571 | DOI:10.2147/IDR.S404855

Ther Adv Cardiovasc Dis. 2023 Jan-Dec;17:17539447231160319. doi: 10.1177/17539447231160319.

ABSTRACT

BACKGROUND: Despite the use of safe and effective conventional drugs, drug therapy problems (DTPs) pose a threat to the successful management of hypertension. DTPs are of a great concern in health care because of their serious consequences such as poor quality of life, increased health care costs, morbidity and mortality. However, there is no published information regarding the prevalence of DTPs and associated factors among hypertensive patients in Uganda.

OBJECTIVE: The aim of the study was to determine the prevalence and factors associated with DTPs among hypertensive patients at the hypertension clinic of Mbarara Regional Referral Hospital (MRRH).

METHOD: A cross-sectional study was conducted at the hypertension clinic, MRRH, Uganda among 228 hypertensive patients. Data were collected from medical records using a data abstraction tool and patients were interviewed using a structured questionnaire. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 22.0. Descriptive analysis was used to determine the prevalence of DTPs. Logistic regression was used to determine the association between the independent and dependent variables. Variables were considered statistically significant at p-value <0.05.

RESULTS: A total of 178 DTPs were identified among 141 hypertensive patients. The prevalence of antihypertensive-related DTPs was 61.8% (95% confidence interval [CI]: 55.3-67.5) with an average of 1.26 ± 0.52 DTPs per patient. Out of 141 participants with DTPs, 109 (77.3%) had one DTP, 27 (19.1%) had 2 DTPs, and 5 (3.5%) had 3 DTPs. The most common types of antihypertensive-related DTPs were 'dosage too low' which accounted for 53 (29.8%), followed by 'adverse drug reactions' which accounted for 48 (27%). Uncontrolled blood pressure (BP; adjusted odds ratio [AOR]: 4.17; 95% CI: 2.33-7.45, p < 0.001) and routine laboratory test results (AOR: 1.87; 95% CI: 1.04-3.36, p = 0.036) were significantly associated with antihypertensive-related DTPs among hypertensive patients.

CONCLUSION: Almost two-thirds of study participants had antihypertensive-related DTPs. The most common DTPs were 'dosage too low' and 'adverse drug reactions' which both accounted for almost a third of the total DTPs each. Uncontrolled BP and routine laboratory test results were significantly associated with antihypertensive-related DTPs among the study participants. Our study emphasizes the need for improved patient care by clinical pharmacists to identify and prevent DTPs among hypertensive patients.

PMID:37036058 | DOI:10.1177/17539447231160319