Drugs Context. 2022 Oct 21;11:2022-6-3. doi: 10.7573/dic.2022-6-3. eCollection 2022.

ABSTRACT

The differential diagnosis of non-coeliac enteropathies (NCEs) is challenging and includes a wide range of aetiologies. Drug-induced NCEs are relatively common and characterized by duodenal villous atrophy, which resolves upon suspension of the offending drug. Immune-checkpoint inhibitors (ICIs), targeting molecules involved in the activation of cytotoxic T cells by targeting, for example, PD-1, PD-L1 and CTLA4, are increasingly used for many types of cancers. Adverse events occurring in the gastrointestinal tract have been described, predominantly in the form of immune-mediated colitis mimicking inflammatory bowel disease. Small bowel involvement whilst on ICI therapy is also possible, though less well described. Herein, we describe two cases of enteropathy with villous atrophy and negative coeliac serology due to ICIs: a 65-year-old man affected by stage IV pulmonary adenocarcinoma under treatment with pembrolizumab and an 18-year-old woman affected by stage IV auricular melanoma who was treated with nivolumab. We also provide a review of the current literature describing small bowel involvement during therapy with ICIs, alone or in combination, for different types of solid tumours. Implications for clinical practice include considering the possibility of small bowel involvement in oncological patients treated with ICIs and the inclusion of ICIs amongst the iatrogenic causes of NCE with villous atrophy. Enteropathies due to ICIs may also represent a pathogenetic model for the understanding of the molecular mechanisms leading to villous atrophy in NCE.

PMID:36339292 | PMC:PMC9616105 | DOI:10.7573/dic.2022-6-3

Cureus. 2022 Oct 3;14(10):e29857. doi: 10.7759/cureus.29857. eCollection 2022 Oct.

ABSTRACT

Bupropion is one of the most commonly prescribed antidepressant medications by physicians all over the world. Because of its favorable sexual profile, it is used as an alternative to serotonin reuptake inhibitors (SSRIs). Its significance in smoking cessation is also well recognized. However, it is associated with a few side effects, such as dizziness, anxiety, tremors, nausea, and insomnia. We present the case of a 54-year-old chronic smoker who developed acute facial dystonia involving the temporomandibular joint (TMJ) after being prescribed 300 mg of bupropion. The Naranjo scale was used to assess the probability of bupropion-induced dystonia. Following the diagnosis, the drug was stopped, and the dystonia completely resolved within one week. At her follow-ups, the patient was found to have no recurrence of dystonia.

PMID:36337825 | PMC:PMC9627898 | DOI:10.7759/cureus.29857

Cureus. 2022 Oct 1;14(10):e29809. doi: 10.7759/cureus.29809. eCollection 2022 Oct.

ABSTRACT

Beta-blockers are well-known for their wide range of therapeutic applications, particularly in patients with cardiac diseases. Physicians worldwide are aware of their potential side effects, including hypoglycemia, dizziness, slow heart rate, fatigue, and heart block. We report a case of erythrodermic psoriasis caused by beta-blockers in a 61-year-old woman with no prior history of the skin condition. The diagnosis was made based on the characteristic histopathological picture and a Naranjo score of 6. She was administered 15 mg of methotrexate weekly and received supportive care. She recovered completely within two months and exhibited no recurrence of symptoms.

PMID:36337823 | PMC:PMC9621099 | DOI:10.7759/cureus.29809

Crit Care Nurs Clin North Am. 2022 Dec;34(4):361-371. doi: 10.1016/j.cnc.2022.08.005.

ABSTRACT

Medications are a common cause of injury to the kidney and can contribute to the increased progression of disease, poorer outcomes, and increased health care costs. Improved prescribing practices can decrease the risk for the development of acute kidney injury and the progression to end-stage kidney disease. KDIGO Clinical Practice Guidelines recommend the use of caution when prescribing potentially nephrotoxic medications for patients with kidney disease. More than 50-72% of individuals across all stages of kidney disease utilized potentially nephrotoxic medications contributing to poorer outcomes. Annually, 1.5 million adverse drug events causing medication-induced nephrotoxicity occur in the US. Medication-induced nephrotoxicity accounts for 14-26% of cases of AKI in adults and 16% of hospitalized children. It is imperative that nurses and all health care providers are practicing nephrotoxic stewardship to prevent medication-induced nephrotoxicity.

PMID:36336427 | DOI:10.1016/j.cnc.2022.08.005

BMC Cancer. 2022 Nov 5;22(1):1136. doi: 10.1186/s12885-022-10199-x.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC).

METHODS: This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes.

RESULT: Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients.

CONCLUSION: In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

PMID:36335320 | PMC:PMC9636611 | DOI:10.1186/s12885-022-10199-x

Ann Clin Psychiatry. 2022 Nov;34(4):217-219. doi: 10.12788/acp.0084.

NO ABSTRACT

PMID:36331562 | DOI:10.12788/acp.0084

Drug Ther Bull. 2022 Sep 6:dtb-2022-000049. doi: 10.1136/dtb.2022.000049. Online ahead of print.

ABSTRACT

Overview of: Tita AT, Szychowski JM, Boggess K, et al Treatment for mild chronic hypertension during pregnancy. N Engl J Med 2022;386:1781-92.

PMID:36332943 | DOI:10.1136/dtb.2022.000049

J Infect Dev Ctries. 2022 Oct 31;16(10):1660-1663. doi: 10.3855/jidc.16594.

ABSTRACT

INTRODUCTION: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity.

CASE REPORT: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up.

CONCLUSIONS: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population.

PMID:36332223 | DOI:10.3855/jidc.16594

Ann Med. 2022 Dec;54(1):3085-3095. doi: 10.1080/07853890.2022.2139411.

ABSTRACT

OBJECTIVES: Extensive application of anti-HER2 targeted therapy improves significantly the HER2-positive advanced breast cancer (BC) prognosis, however, it is still difficult to treat brain metastasis. In current study, we explored effective approaches via combining pyrotinib to treat brain metastasis in patients with HER2-positive advanced BC based upon clinical data.

MATERIALS AND METHODS: Current study included 61 HER2-positive BC patients with brain metastases (BM) who were treated by pyrotinib-based regimens. The systemic regimens included pyrotinib combined with capecitabine, pyrotinib combined with nab-paclitaxel, and pyrotinib combined with vinorelbine. Patients' progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and objective response rate (ORR), as well as drug-related adverse events (AEs) in regard of each combination regimen were analyzed.

RESULTS: Pyrotinib-based systemic therapy resulted in 8.6 months median PFS (mPFS) and 18.0 months median OS (mOS) among the BM patients. Regarding different regimens, the combination of pyrotinib with nab-paclitaxel was superior to the combination with capecitabine and vinorelbine with respect to PFS and OS. The central nervous system (CNS) ORR did not showcase significant difference among 3 regimens, however, nab-paclitaxel combined regimen obtained the best peripheral ORR (84.6%) (p ≤ .05).

CONCLUSIONS: Pyrotinib-based combination therapy is safe for HER2-positive brain metastasis treatment. Compared with vinorelbine or capecitabine, pyrotinib combined with nab-paclitaxel is more effective with less toxicity, which is the preferable regimen for HER2-positive brain metastasis.KEY MESSAGESPresent investigation investigated effective methods through combining pyrotinib to treat brain metastasis with HER2-positive advanced brain cancer. The outcomes verified that pyrotinib-based combination therapy was safe and efficient to treat HER2-positive brain metastasis. Therefore, it is effective to treat brain metastasis applying anti-HER2 targeted therapies although pyrotinib showcases efficiency regarding its treatments for the metastasis.

PMID:36331291 | DOI:10.1080/07853890.2022.2139411

Rev Esp Salud Publica. 2022 Nov 3;96:e202211085.

ABSTRACT

OBJECTIVE: Energy drinks generally contain caffeine and other stimulants, commercially aimed at young people. Previous research suggests that its effects on adolescents health are dangerous. The aim of the study was to evaluate the effect of taurine and caffeine consumption from energy drinks on adolescent health and to identify patterns of consumption and, their association with physiological symptoms.

METHODS: A cross-sectional study of a convenience sample of students (n=135) aged 16 to 17 years was conducted in the State of Hidalgo, Mexico. A self-administered online questionnaire was used from September to November 2020 to report energy drink consumption patterns, perceived effects, and psychophysiological symptoms. The statistical analysis of questionnaire content was made by interjudges evaluation. A concordance index (Cohen-Fleiss Kappa coefficient) was applied for consumption patterns, bivariate correlation tests, Pearson correlation coefficients for levels (very high, moderate, low) of caffeine and taurine were used in the items applied to the target population and Spearmans rho for physiological and psychological effects.

RESULTS: The participants (mean age: 16 years; 57.8% of women) reported having consumed energy drinks at least once. Only 26.7% of adolescents (n=36) reported that they had never consumed. The average consumption of energy drinks was once per month (24.4%). A statistically significant correlation was found between the consumption of drinks with taurine and the physical effects (tremors and chest pain) and caffeinated beverages with psychophysiological (fatigue, excessive urination, insomnia, and feeling of lack of rest).

CONCLUSIONS: The study findings indicate associations between energy drink consumption and the presence of adverse psychological and physical symptoms in adolescents.

PMID:36325955

Oral Oncol. 2022 Oct 31;135:106231. doi: 10.1016/j.oraloncology.2022.106231. Online ahead of print.

ABSTRACT

OBJECTIVES: Molecular targeted therapies against vascular endothelial growth factor (VEGF) receptor (VEGFR) have been explored in the treatment of recurrent or metastatic nasopharyngeal carcinoma (rmNPC). We conducted a meta-analysis to evaluate the efficacy and safety of VEGF/VEGFR inhibitors for treating rmNPC.

MATERIALS AND METHODS: Electronic databases were searched for eligible literature. Data on the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), PFS rate, OS rate, and drug-related adverse events (AEs) were extracted.

RESULTS: A total of 10 studies (published in 9 articles) that involved 357 patients were included. The pooled ORR was 37 % (95 % confidence interval [CI]: 17-60 %), the DCR was 70 % (95 % CI: 51-85 %), the mPFS was 5.69 months (95 % CI: 4.52-6.86), the mOS was 12.61 months (95 % CI: 10.23-14.99), the 1-year PFS rate was 34 % (95 % CI: 25-44 %), and the 1-year OS rate was 62 % (95 % CI: 38-83 %). The pooled incidence of grade 3/4 drug-related AEs was 27 %, while that of grade 5 AEs was 0.22 %. Further subgroup analysis showed that the pooled ORR and DCR for first-line VEGF inhibitors were 80 % (95 % CI: 74-86 %) and 94 % (CI: 82-100 %), respectively.

CONCLUSION: Our meta-analysis is the first report to demonstrate the efficacy and safety of VEGF/VEGFR inhibitors in patients with rmNPC. Targeting VEGF/VEGFR therapy added to first-line chemotherapy achieved an excellent ORR and DCR, while the improvement in response rates did not translate to a prominent OS benefit.

PMID:36327674 | DOI:10.1016/j.oraloncology.2022.106231

Front Pediatr. 2022 Oct 12;10:982179. doi: 10.3389/fped.2022.982179. eCollection 2022.

ABSTRACT

OBJECTIVES: To assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem.

METHODS: The following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found.

RESULTS: Fifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with β-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99-1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97-1.20) between ertapenem and other carbapenems. Compared with β-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71-1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31-1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59-4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events.

CONCLUSION: Our findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.

PMID:36324821 | PMC:PMC9620802 | DOI:10.3389/fped.2022.982179

BMJ Open. 2022 Nov 2;12(11):e062853. doi: 10.1136/bmjopen-2022-062853.

ABSTRACT

INTRODUCTION: Adverse drug events (ADEs) among hospitalised older adults are common yet often preventable. Efforts to recognise ADEs using pharmacist review and electronic health record adaptations have had mixed results. Our health system developed and implemented a geriatric prescribing context designed to offer age-friendly dose and frequency defaults for hospitalised patients 75 years and older. The impact of this context on ADEs remains unknown. To measure its impact, our team created a list of ADE-related International Classification of Diseases (ICD) codes specific to 10 commonly used medications at our institution. This protocol paper presents the process of designing a screening tool for ADEs, validating the tool with manual chart reviews and measuring the impact of the context on ADEs.

METHODS AND ANALYSIS: This retrospective cross-sectional study will assess our list of ICD-10 codes against manual chart review to determine its accuracy. An electronic health record report for patients aged 75 years and older admitted to the hospital for a minimum of two nights was generated to identify 100 test positives and 100 test negatives. Test positives need at least one code from each level of our ICD-10 code list. The first level of codes identifies any possible ADEs while the second level is more symptom based. Test negatives must not have any code from the list. Two physicians blinded to test status will complete a structured chart review to determine if a patient had an ADE during their hospitalisation. Acceptable inter-rater reliability will need to be met before proceeding with independent chart review. Positive predictive value and negative predictive value will be calculated once all the chart reviews are completed.

ETHICS AND DISSEMINATION: The Oregon Health & Science University Institutional Review Board approved this study (#21385). The results of the study will be disseminated in peer-reviewed journals and conference presentations.

PMID:36323472 | DOI:10.1136/bmjopen-2022-062853

Expert Rev Gastroenterol Hepatol. 2022 Nov 2. doi: 10.1080/17474124.2022.2143346. Online ahead of print.

ABSTRACT

OBJECTIVE: Different classes of medication have been reported in the literature to be associated with an increased risk of gastrointestinal perforation. However, little is known about the risk of drug-induced perforated appendicitis.

METHODS: We analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS), a large national database of reported adverse events associated with post-market FDA-approved medications from Jan 2011 through Oct 2021. Patients of any age group with appendiceal perforation were included. Duplicated reports and other anatomical areas of gastrointestinal tract perforation outside the appendix were excluded.

RESULTS: During the study period, 474 event cases met inclusion criteria, of which 284 were females. Most reports of perforation occurred in patients 40-49 years (n=110) and 50-59 years (n=144). Cases of perforated appendicitis occurred in patients being treated for multiple sclerosis (31.5%) and rheumatoid arthritis (17.1%). Perforation occurred in patients receiving interferon beta 1a (23.6%), adalimumab (17.9%), etanercept (14.1%), natalizumab (12.2%), clozapine (10.1%), infliximab (9.9%), bevacizumab (7.2%), and calcium chloride (4.9%). Sixteen fatal outcomes were reported.

CONCLUSION: Findings from the FAERS database highlight the risk of appendiceal perforation in the context of different classes of drugs. Larger pharmacovigilance studies are needed to confirm these observations as well as overcome inherent reporting biases.

PMID:36322707 | DOI:10.1080/17474124.2022.2143346

Rev Panam Salud Publica. 2022 Oct 25;46:e166. doi: 10.26633/RPSP.2022.166. eCollection 2022.

ABSTRACT

OBJECTIVE: To identify central nervous system (CNS) adverse events potentially associated with prophylaxis or drug treatment for COVID-19, and to describe the characteristic of the individuals affected.

METHODS: A scoping review was performed using a search strategy to retrieve articles from PubMed, EMBASE, SciELO, Scopus, CINAHL and BVS databases. Studies reporting on individuals receiving prophylactic or curative drugs for COVID-19 with at least one CNS adverse event were included. Articles reporting on CNS adverse events associated with medication for other health conditions were excluded.

RESULTS: The search retrieved 1 547 articles, eight of which met the inclusion criteria. Seven studies had an observational design. A total of 3 035 individuals were assessed, of whom 1 701 were health care professionals and 1 978 were women. Curative treatment with hydroxychloroquine, chloroquine, lopinavir/ritonavir, and azithromycin was the most frequent (n = 5). The most common adverse events were headache, dizziness, mood disturbances, and drowsiness. Suicide was the most frequent severe event. Six adverse events were unexpected for hydroxychloroquine, chloroquine, and doxycycline.

CONCLUSION: Potential CNS adverse events were unspecific and in general potentially associated with the use of hydroxychloroquine (monotherapy or associated with antibiotics). The data confirm the unfavorable risk/benefit profile of these drugs for the prevention and management of signs and symptoms of SARS-CoV-2 infection.

PMID:36320207 | PMC:PMC9595226 | DOI:10.26633/RPSP.2022.166

PLoS One. 2022 Nov 1;17(11):e0272022. doi: 10.1371/journal.pone.0272022. eCollection 2022.

ABSTRACT

BACKGROUND: Treatment options for many cancers include immune checkpoint inhibitor (ICI) monotherapy and combination therapy with impressive clinical benefit across cancers. We sought to define the comparative cardiac risks of ICI combination and monotherapy.

METHODS: We used VigiBase, the World Health Organization pharmacovigilance database, to identify cardiac ADRs (cADRs), such as carditis, heart failure, arrhythmia, myocardial infarction, and valvular dysfunction, related to ICI therapy. To explore possible relationships, we used the reporting odds ratio (ROR) as a proxy of relative risk. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more ADRs are observed than expected due to chance.

RESULTS: We found 2278 cADR for ICI monotherapy and 353 for ICI combination therapy. Combination therapy was associated with significantly higher odds of carditis (ROR 6.9, 95% CI: 5.6-8.3) versus ICI monotherapy (ROR 5.0, 95% CI: 4.6-5.4). Carditis in ICI combination therapy was fatal in 23.4% of reported ADRs, compared to 15.8% for ICI monotherapy (P = 0.058).

CONCLUSIONS: Using validated pharmacovigilance methodology, we found increased odds of carditis for all ICI therapies, with the highest odds for combination therapy. Given the substantial risk of severe ADR and death, clinicians should consider these findings when prescribing checkpoint inhibitors.

PMID:36318537 | PMC:PMC9624428 | DOI:10.1371/journal.pone.0272022

Medicine (Baltimore). 2022 Oct 28;101(43):e31296. doi: 10.1097/MD.0000000000031296.

ABSTRACT

BACKGROUND: Nefopam is a non-opioid, non-nonsteroidal anti-imflammatory drug, analgesic drug that inhibits the reuptake of serotonin, norepinephrine, and dopamine. It is widely used as an adjuvant for pain. This study investigated whether the intraoperative, intravenous infusion of nefopam (20 mg) reduces postoperative morphine consumption, pain scores, and alleviates neuropathic pain in patients undergoing cervical spine surgery.

METHODS: A prospective, paralleled design, randomized study was conducted on 50 patients (aged 18-75 years) in a university-based hospital. The patients were assigned to an intervention or a control group (25 patients in each). The intervention group received a 1-hour infusion of nefopam (20 mg) before the end of surgery. The control group received normal saline (NSS). The outcome measures were morphine consumption during the first 24 postoperative hours, numerical rating scale (NRS) pain scores, and scores for the Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T) in patients with neuropathic pain and adverse drug reactions. The NPSI-T scores were assessed on the preoperative day, postoperative day 1, 3, 15, and 30. The outcome assessors were blinded to group allocation.

RESULTS: Fifty patients were analyzed. During the first 24 postoperative hours, morphine consumption was 8 mg (nefopam) and 12 mg (NSS; P = .130). The intervention and control groups demonstrated no significant differences in the median NRS scores or total NPSI-T scores or adverse drug reactions.

CONCLUSIONS: A single, intraoperative infusion of 20 mg of nefopam did not significantly reduce postoperative (24 hours) morphine consumption in patients undergoing anterior cervical spine surgery.

PMID:36316913 | DOI:10.1097/MD.0000000000031296

Respir Res. 2022 Oct 31;23(1):299. doi: 10.1186/s12931-022-02218-z.

ABSTRACT

BACKGROUND: The effect of ambient temperature on respiratory mortality has been consistently observed throughout the world under different climate change scenarios. Countries experiencing greater inter-annual variability in winter temperatures (and may not be lowest winter temperatures) have greater excess winter mortality compared to countries with colder winters. This study investigates the association between temperature and respiratory deaths in Malta which has one of the highest population densities in the world with a climate that is very hot in summer and mild in winter.

METHODS: Daily number of respiratory deaths (7679 deaths) and meteorological data (daily average temperature, daily average humidity) were obtained from January 1992 to December 2017. The hot and cold effects were estimated at different temperatures using distributed lag non-linear models (DLNM) with a Poisson distribution, controlling for time trend, relative humidity and holidays. The reference temperature (MMT) for the minimum response-exposure relationship was estimated and the harvesting effects of daily temperature (0-27 lag days) were investigated for daily respiratory mortality. Effects were also explored for different age groups, gender and time periods.

RESULTS: Cooler temperatures (8-15 °C) were significantly related to higher respiratory mortality. At 8.9 °C (1st percentile), the overall effect of daily mean temperature was related to respiratory deaths (RR 2.24, 95%CI 1.10-4.54). These effects were also found for males (95%CI 1.06-7.77) and males across different age groups (Males Over 65 years: RR 4.85, 95%CI 2.02-11.63 vs Males between 16 and 64 years: RR 5.00, 95%CI 2.08-12.03) but not for females. Interestingly, colder temperatures were related to respiratory deaths in the earliest time period (1992-2000), however, no strong cold effect was observed for later periods (2000-2017). In contrast, no heat effect was observed during the study period and across other groups.

CONCLUSIONS: The higher risk for cold-related respiratory mortality observed in this study could be due to greater inter-annual variability in winter temperatures which needs further exploration after adjusting for potential physical and socio-demographic attributes. The study provides useful evidence for policymakers to improve local warning systems, adaptation, and intervention strategies to reduce the impact of cold temperatures.

PMID:36316676 | DOI:10.1186/s12931-022-02218-z

BMC Gastroenterol. 2022 Oct 31;22(1):441. doi: 10.1186/s12876-022-02542-0.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide every year, and most HCC patients are diagnosed with advanced disease and can only receive systemic treatment. TKIs are the most important components of the systemic treatment of HCC and have both good efficacy and adverse events (AEs). METHODS: This analysis included 207 patients with locally advanced unresectable or metastatic HCC who received oral treatment with apatinib. We analyzed the overall survival (OS) and progression-free survival (PFS) of patients with or without corresponding AEs to evaluate which AEs can predict the efficacy of apatinib.

RESULTS: Patients with hand-foot syndrome (HFS; p = 0.005), proteinuria (p = 0.006) and diarrhea (p < 0.001) had significantly better OS than those without corresponding AEs, and the appearance of HFS (p = 0.006) and proteinuria (p = 0.004) was associated with longer PFS.

CONCLUSION: Among all the AEs induced by apatinib in the treatment of advanced HCC, proteinuria could potentially predict PFS, and diarrhea was a potential predictor of OS.

PMID:36316630 | DOI:10.1186/s12876-022-02542-0

Int J Med Sci. 2022 Oct 9;19(12):1816-1823. doi: 10.7150/ijms.76139. eCollection 2022.

ABSTRACT

Adverse drug events due to drug-drug interactions can be prevented by avoiding concomitant use of causative drugs; therefore, it is important to understand drug combinations that cause drug-drug interactions. Although many attempts to identify drug-drug interactions from real-world databases such as spontaneous reporting systems have been performed, little is known about drug-drug interactions caused by three or more drugs in polypharmacy, i.e., multiple drug-drug interactions. Therefore, we attempted to detect multiple drug-drug interactions using decision tree analysis using the Japanese Adverse Drug Event Report (JADER) database, a Japanese spontaneous reporting system. First, we used decision tree analysis to detect drug combinations that increase the risk of rhabdomyolysis in cases registered in the JADER database that used six statins. Next, the risk of three or more drug combinations that significantly increased the risk of rhabdomyolysis was validated with in vivo experiments in rats. The analysis identified a multiple drug-drug interaction signal only for pitavastatin. The reporting rate of rhabdomyolysis for pitavastatin in the JADER database was 0.09, and it increased to 0.16 in combination with allopurinol. Furthermore, the rate was even higher (0.40) in combination with valsartan. Additionally, necrosis of leg muscles was observed in some rats simultaneously treated with these three drugs, and their creatine kinase and myoglobin levels were elevated. The combination of pitavastatin, allopurinol, and valsartan should be treated with caution as a multiple drug-drug interaction. Since multiple drug-drug interactions were detected with decision tree analysis and the increased risk was verified in animal experiments, decision tree analysis is considered to be an effective method for detecting multiple drug-drug interactions.

PMID:36313225 | PMC:PMC9608045 | DOI:10.7150/ijms.76139