Adverse Effects Of Treatment Research Articles

Effects of supervised exercise and self-managed psychosexual therapy on sexual health in men with prostate cancer: A randomized clinical trial.

71 Background: Sexual dysfunction is a common, distressing, and persistent adverse effect of prostate cancer treatment and current management strategies do not adequately address physical and psychological effects. Exercise is emerging as potential therapy in the management of sexual health. The purpose of this study was to investigate the effects of supervised, clinic-based, resistance and aerobic exercise with and without psychosexual therapy self-management on sexual health in men with prostate cancer. Methods: A 3-arm, parallel group, multi-center randomized clinical trial was undertaken between 2014 and 2018. The study was conducted at university-affiliated exercise clinics. Eligible participants were men with prostate cancer who had previously or were currently undergoing treatment and concerned about sexual dysfunction. One-hundred and twelve participants were randomized to: 1) 6 months of supervised, group-based resistance and aerobic exercise (n=39), 2) the same exercise program plus psychosexual therapy (n=36), or 3) usual care (n=37). Exercise was undertaken 3 days per week at university-affiliated exercise clinics. Psychosexual therapy consisted of a brief self-management intervention that addressed psychological and sexual wellbeing. The primary outcome was sexual health assessed with the International Index of Erectile Function. Secondary outcomes included body composition, physical function, and muscle strength. Analyses were undertaken using an intention-to-treat approach. Results: Erectile function increased by 5.1 points (exceeds MICD) with exercise and 1.0 point with usual care (P interaction=.010) while intercourse satisfaction increased by 2.2 points with exercise and 0.2 points with usual care (P interaction=.026). Self-managed psychosexual therapy did not result in additional improvements. Compared with usual care, exercise prevented an increase in fat mass (P interaction=.028) and improved physical function outcomes, as well as upper and lower body muscle strength. Conclusions: Supervised resistance and aerobic exercise improved erectile function and intercourse satisfaction in men with prostate cancer; however, self-managed psychosexual therapy resulted in no additional improvements. Men with prostate cancer concerned about sexual dysfunction should be encouraged to undertake exercise as a potential countermeasure. Clinical trial information: ACTRN12613001179729 .

Efficacy and Safety of Flumatinib in Treatment of Patients with Chronic Myeloid Leukemia

To analyze the efficacy and safety of flumatinib in the treatment of patients with chronic myeloid leukemia (CML). The clinical data of 56 CML patients treated with flumatinib from January 2020 to December 2021 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. Patients were divided into three groups: 35 new diagnosed CML patients treated with flumatinib (group A), 10 patients with imatinib/dasatinib intolerance (group B) and 11 patients with imatinib/dasatinib resistance (group C) switched to flumatinib treatment, respectively. The molecular response and adverse effects of flumatinib treatment were evaluated. In group A, the early molecular response (EMR) at 3 months was 40.0%, and the major molecular response (MMR) at 6 and 12 months was 43.7% and 46.2%, respectively. In group B, the EMR was 50.0% at 3 months, and the MMR was 70.0% and 66.2% at 6 and 12 months, respectively. Among evaluable patients, 6 cases in group B achieved molecular response of 4.5 (MR4.5) at 12 months after switching to flumatinib treatment. In group C, 3 cases who switched from imatinib resistance to flumatinib achieved MR4.5 at 12 months, but 2 cases who switched from dasatinib resistance to flumatinib failed. Subgroup analysis showed significant differences in EUTOS long-term survival (ELTS) scores for patients in the medium-risk/high-risk group compared with those in the low-risk group for 3-month EMR (18.8% vs 57.9%), 6-month MMR (15.4% vs 63.2%) and 12-month MR4.5 (15.4% vs 69.2%) (P =0.036, P =0.012,P =0.015). The most common adverse effect in group A was thrombocytopenia, accounting for 54.5%, and 22.8% (8/35) patients discontinued the drug due to haematological adverse effects. Compared with patients who did not discontinue the drug or whose recovery time from discontinuation due to haematological toxicity was <1 month, patients whose recovery time from discontinuation was ≥1 month had a significantly worse 3-month EMR, 6-month MMR and 12-month MR4.5 (P =0.028, P =0.021, P =0.002). Flumatinib has better molecular response and tolerance in patients with primary, imatinib/dasatinib-intolerant or resistant CML. Medium-risk/high-risk in ELTS score and time to recovery from discontinuation due to haematological toxicity ≥1 month are important factors influencing achievement of better molecular response in flumatinib treatment.

Formulation and evaluation of solid lipid nanoparticles loaded with papaya seed chloroform extract for long-term antifertility effects on the male rat, Bandicota bengalensis

The study is the first to formulate and investigate potential of papaya seed chloroform extract based solid lipid nanoparticles (PSCEN) as antifertility agents on male Bandicota bengalensis. The prepared nanoparticles were spherical of size 300–600 nm. The release kinetics showed a controlled release of the drug with major release over 48 h. To assess the antifertility effects of PSCEN, adult male rats were fed a diet containing two different concentrations of PSCEN (5% and 10%) for 15 days under bi-choice conditions. The mean total active ingredient ingestion of the rats in the two treated groups ranged from 2.13–3.31 and 3.92–5.87 g/100g body weight, respectively. No adverse effects of treatment on body weight were observed. Also, no mortality of rats was observed. The treatment had a significant effect on the weight of the testis and the epididymis, but not on the other organs. Sperm motility (%), sperm viability (%), sperm count (millions/ml), sperm mitochondrial activity (%), sperm nuclear chromatin de-condensation (%) and sperm hypo-osmotic swelling (%) were significantly decreased, and sperm abnormality (%) significantly increased compared to the vehicle control group. The reproductive success rates of male rats treated with 5% and 10% PSCEN and mated with untreated female rats were 20.00–66.67% and 16.67%, respectively, while in untreated female rats mated with male rats of vehicle control group, reproductive success rate was 33.33 to 80%. The study found a maximal antifertility effect of the 10% PSCEN containing bait, which was irreversible up to 105 days after stopping treatment, suggesting long-term efficacy.

Early-life prophylactic antibiotic treatment disturbs the stability of the gut microbiota and increases susceptibility to H9N2 AIV in chicks

BackgroundAntibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment.ResultsUnexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection.ConclusionsOur data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management.Ao91n5eHkkQPyDkUXXsk_bVideo

BDNF/TrkB pathway activation in D1 receptor-expressing striatal projection neurons plays a protective role against L-DOPA-induced dyskinesia

L-DOPA-induced dyskinesia (LID) is a frequent adverse side effect of L-DOPA treatment in Parkinson's disease (PD). Understanding the mechanisms underlying the development of these motor disorders is needed to reduce or prevent them. We investigated the role of TrkB receptor in LID, in hemiparkinsonian mice treated by chronic L-DOPA administration. Repeated L-DOPA treatment for 10 days specifically increased full-length TrkB receptor mRNA and protein levels in the dopamine-depleted dorsal striatum (DS) compared to the contralateral non-lesioned DS or to the DS of sham-operated animals. Dopamine depletion alone or acute L-DOPA treatment did not significantly increase TrkB protein levels. In addition to increasing TrkB protein levels, chronic L-DOPA treatment activated the TrkB receptor as evidenced by its increased tyrosine phosphorylation. Using specific agonists for the D1 or D2 receptors, we found that TrkB increase is D1 receptor-dependent. To determine the consequences of these effects, the TrkB gene was selectively deleted in striatal neurons expressing the D1 receptor. Mice with TrkB floxed gene were injected with Cre-expressing adeno-associated viruses or crossed with Drd1-Cre transgenic mice. After unilateral lesion of dopamine neurons in these mice, we found an aggravation of axial LID compared to the control groups. In contrast, no change was found when TrkB deletion was induced in the indirect pathway D2 receptor-expressing neurons. Our study suggests that BDNF/TrkB signaling plays a protective role against the development of LID and that agonists specifically activating TrkB could reduce the severity of LID.

Medical treatment of eosinophilic esophagitis.

Medical treatment of eosinophilic esophagitis.

The Association of Oxaliplatin-Containing Adjuvant Chemotherapy Duration with Overall and Cancer-Specific Mortality in Individuals with Stage III Colon Cancer: A Population-Based Retrospective Cohort Study.

Few studies have examined the relationship between duration of oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer and mortality in routine practice. We examined the association between treatment with 50% versus >85% of a maximal course of adjuvant therapy (eight cycles of CAPOX, twelve cycles of FOLFOX) and mortality in stage III colon cancer. Using linked databases, we identified Ontarians aged ≥18 years at diagnosis of stage III colon cancer between 2007 and 2019. In the primary comparison, we compared patients who received 50% or >85% of a maximal course of adjuvant therapy; in a secondary comparison, we evaluated a dose effect across patients who received FOLFOX in one-cycle increments from six to ten cycles against >85% (more than ten cycles) of a maximal course of FOLFOX. The main outcomes were overall and cancer-specific mortality. Follow-up began 270 days after adjuvant treatment initiation and terminated at the first of the outcome of interest, loss of eligibility for Ontario's Health Insurance Program, or study end. Overlap propensity score weights accounted for baseline between-group differences. We determined the hazard ratio, estimating the association between mortality and treatment. Non-inferiority was concluded in the primary comparison for either outcome if the upper limit of the two-sided 95% CI was ≤1.11, which is the margin used in the International Duration Evaluation of Adjuvant Chemotherapy Collaboration. We included 3546 patients in the analysis of overall mortality; 486 (13.7%) received 50% and 3060 (86.3%) received >85% of a maximal course of therapy. Median follow-up was 5.4 years, and total follow-up was 20,510 person-years. There were 833 deaths. Treatment with 50% of a maximal course of adjuvant therapy was associated with a hazard ratio of 1.13 (95% CI 0.88 to 1.47) for overall mortality and a subdistribution hazard ratio of 1.31 (95% CI 0.91 to 1.87) for cancer-specific mortality versus >85% of a maximal course of therapy. In the secondary comparison, there was a trend toward higher overall mortality in patients treated with shorter durations of therapy, though confidence intervals overlapped considerably. We could not conclude that treatment with 50% of a maximal course is non-inferior to >85% of a maximal course of adjuvant therapy for mortality in stage III colon cancer. Clinicians and patients engaging in decision-making around treatment duration in this context should carefully consider the trade-off between treatment effectiveness and adverse effects of treatment.

Amiodarone accumulates two cholesterol precursors in myocardium: A controlled clinical study.

Amiodarone is an effective antiarrhythmic drug, which interferes with cholesterol synthesis. In the human body, it inhibits two enzymes in the cholesterol-synthesis pathway, followed by increases especially in serum desmosterol and zymostenol concentrations and a decrease in that of serum lathosterol. We explored whether desmosterol and zymostenol accumulate also in myocardial tissue during amiodarone treatment. Thirty-three patients admitted for cardiac transplantation volunteered for the study. Ten patients were on amiodarone treatment (AD group) and 23 were not (control group). The groups were matched as regards demographic and clinical variables. Myocardial samples were obtained from the removed hearts from 31 patients. Cholesterol, non-cholesterol sterols and squalene were quantified by means of gas-liquid chromatography. In serum and myocardium, desmosterol was 19- and 18-fold higher and zymostenol 4- and 2-fold higher in the AD group versus the control group (p<0.001 for all). In contrast, myocardial cholesterol, squalene and lathosterol levels were lower in the AD group than in the control group (p<0.05 for all). Levels of phytosterols and cholestanol were similar in the serum and myocardium in the two groups. Levels of myocardial and serum desmosterol, zymostenol, lathosterol and phytosterols correlated with each other in both groups (p<0.05 for all). Amiodarone treatment caused the accumulation of desmosterol and zymostenol in myocardium. In particular, myocardial desmosterol concentrations were substantially elevated, which may play a part in some of the therapeutic and adverse effects of amiodarone treatment.

Nanoliposomal oxaliplatin ameliorates chemotherapy-induced neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is an important adverse effect of treatment with oxaliplatin (OXA). We have developed PEGylated nanoliposomal oxaliplatin (OXA-LIP) and tested its activity in an animal model of CIPN. OXA-LIPs were prepared using a combination of egg yolk lecithin, cholesterol, and DSPE-mPEG2000 (at ratios 400, 80, and 27 mg). These liposomes were characterized using several different methods (e.g., polydispersity index (PDI), and zeta potential, FESEM). The in vivo study was performed in 15 male rats comprising three groups: a negative control (normal saline) OXA, and OXA-LIP. These were injected intraperitoneally at a concentration of 4 mg/kg on two consecutive days every week, for 4 weeks. After that, CIPN was assessed using the hotplate and acetonedropmethods. Oxidative stress biomarkers such as SOD, catalase, MDA, and TTG were measured in the serum samples. The functional disturbances of the liver and kidney were assessed by measuring the serum levels of ALT, AST, creatinine, urea, and bilirubin. Furthermore, hematological parameters were determined in the three groups. The OXA-LIP had an average particle size, PDI, and zeta potential of 111.2 ± 1.35 nm, 0.15 ± 0.045, and −52.4 ± 17 mV, respectively. The encapsulation efficiency of OXA-LIP was 52% with low leakage rates at 25 °C.Thermal hyperalgesia changes showed OXA has significant effects in the induction of neuropathy on days 7, 14, and 21 compared to the control group. OXA had a significantly greater sensitivity than the OXA-LIP and control groups in the thermal allodynia test (P < 0.001). OXA-LIP administration did not show significant effects on the changes of oxidative stress, biochemical factors, and cell count. Our findings provide a proof of concept on the potential application of oxaliplatin encapsulated with PEGylated nanoliposome to ameliorate the severity of neuropathy, supporting further studies in clinical phases to explore the value of this agent for Chemotherapy-induced peripheral neuropathy.

Seeking adverse effects in systematic reviews of orthodontic interventions: a cross-sectional study (part 1)

BackgroundSystematic reviews that assess the benefits of interventions often do not completely capture all dimensions of the adverse effects. This cross-sectional study (part 1 of 2 studies) assessed whether adverse effects were sought, whether the findings on these effects were reported, and what types of adverse effects were identified in systematic reviews of orthodontic interventions.MethodsSystematic reviews of orthodontic interventions on human patients of any health status, sex, age, and demographics, and socio-economic status, in any type of setting assessing any type of adverse effect scored at any endpoint or timing were eligible. The Cochrane Database of Systematic Reviews and 5 leading orthodontic journals were manually searched for eligible reviews between August 1 2009 and July 31 2021. Study selection and data extraction was conducted by two researchers independently. Prevalence proportions were calculated for four outcomes on seeking and reporting of adverse effects of orthodontic interventions. Univariable logistic regression models were used to determine the association between each one of these outcomes and the journal in which the systematic review was published using the eligible Cochrane reviews as reference.ResultsNinety-eight eligible systematic reviews were identified. 35.7% (35/98) of reviews defined seeking of adverse effects as a research objective, 85.7% (84/98) sought adverse effects, 84.7% (83/98) reported findings related to adverse effects, and 90.8% (89/98) considered or discussed potential adverse effects in the review. Reviews in the journal Orthodontics and Craniofacial Research compared with Cochrane reviews had approximately 7 times the odds (OR 7.20, 95% CI 1.08 to 47.96) to define seeking of adverse effects in the research objectives. Five of the 12 categories of adverse effects accounted for 83.1% (162/195) of all adverse effects sought and reported.ConclusionsAlthough the majority of included reviews sought and reported adverse effects of orthodontic interventions, end-users of these reviews should beware that these findings do not give the complete spectrum on these effects and that they could be jeopardized by the risk of non-systematically assessing and reporting of adverse effects in these reviews and in the primary studies that feed them. Much research is ahead such as developing core outcome sets on adverse effects of interventions for both primary studies and systematic reviews.

The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment.

Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia. We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority. We identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I2=47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations. Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue. The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Schizophrenia and the COVID-19 pandemic: A narrative review from the biomedical perspective.

The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic in 2020 caused a rapid worsening of global mental health. Patients with severe mental disorders, including schizophrenia, are at higher risk of being infected. The neuroinvasive potential of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed. The aim of this article was to present a narrative and comprehensive review of multidimensional associations between schizophrenia and COVID-19 with special emphasis on common biological pathways. Online searches were performed in the PubMed database and covered the publication period until September 17, 2022. Search terms included "psychosis", "schizophrenia", "inflammation" and "COVID-19". Viewed as a neuroinflammatory state, schizophrenia shares several neurobiological mechanisms with the COVID-19. Environmental stress, common comorbidities of schizophrenia and adverse effects of antipsychotic treatment are associated with the higher severity and mortality of the COVID-19. Additionally, more frequent relapses of psychosis have been observed, and might be related to lower treatment adherence. In the context of clinical manifestation, higher level of negative symptoms has been identified among patients with schizophrenia during the pandemic. Improvements in mental health care policy and treatment adjustment are necessary to protect people with schizophrenia who are the population that is particularly vulnerable to the consequences of the COVID-19 pandemic. Future research will show if prenatal infection with the SARS-CoV-2 increases a risk of psychosis.

EFFICACY AND SAFETY OF "SACHI SAHELI" POLYHERBAL FORMULATIONS IN GYNAECOLOGICAL DISORDERS: A PROSPECTIVE, NON-RANDOMISED, OPEN-LABEL STUDY

Background and aim: Symptoms of gynaecological disorders, including dysmenorrhea, leukorrhea, and premenopausal syndrome (PMS), are a common health concern, particularly among women of reproductive age. Due to the adverse effects of conventional treatments, the use of herbal remedies to treat various gynaecological disorders has increased. This study aimed to assess the efficacy and safety of Sachi Saheli formulations in subjects suffering from dysmenorrhea, leucorrhoea, and PMS. Methods: This was a single-arm, open-label, non-randomised prospective study. Female participants were recruited based on the inclusion and exclusion criteria. Study interventions were given to all participants for 90 days. Changes in blood haemoglobin levels were assessed from the baseline to the end of the study. Subjective symptoms and the investigators' severity assessment on 27 questionnaires were evaluated at baseline and the end of the study. Safety was also assessed by measuring liver and kidney function's haematological and biochemical markers. Results: A total of 120 female subjects were enrolled. After treatment with Sachi Saheli syrup and tablets, blood haemoglobin levels increased significantly compared to baseline (p &lt; 0.0001). All subjects showed significant improvement in anxiety, menstrual pain, depression, and vaginal discharge symptoms. A significant improvement in the severity of physical and affective symptoms across 27 parameters was also observed. There were no significant changes observed in laboratory safety parameters. None of the subjects reported any adverse events during the treatment period. Conclusions: Sachi Saheli syrup and tablet may improve the symptoms of dysmenorrhea, leukorrhea and PMS.

Subchronic exposure to Tamoxifen modulates the hippocampal BDNF/ERK/Akt/CREB pathway and impairs memory in intact female rats

Tamoxifen (TAM), a Selective Estrogen Receptor Modulator (SERM), is commonly used to treat and prevent breast cancer. Memory impairment has been noticed in patients who experience hormone therapy in the case of TAM and other SERMs. Animal studies that mimic the TAM longer exposure effects are needed to better elucidate the adverse effects of continuous treatment in humans. This study evaluated the effects of TAM subchronic administration on the memory performance and hippocampal neural plasticity of intact female Wistar rats. Animals were treated intragastrically with TAM (0.25 and 2.5 mg/kg) for 59 days. The rats were subjected to the Object Location Test (OLT) and Object Recognition Test (ORT) to evaluate memory performance. After euthanasia, the hippocampus samples were excised and the protein levels of the BDNF/ERK/Akt/CREB pathway were evaluated. The rat's locomotor activity and hippocampal TrkB levels were similar among the experimental groups. TAM at both doses reduced the memory performance of female rats in the OLT and short-term memory of ORT, and impaired hippocampal levels of mBDNF, proBDNF, and pCREB/CREB. TAM only at the dose of 2.5 mg/kg reduced the memory performance of rats in the long-term memory of ORT and hippocampal pERK/ERK and pAkt/Akt ratios. TAM subchronic administration induced amnesic effects and modulated the hippocampal BDNF/ERK/Akt/CREB pathway in intact young adult female Wistar rats.

Review on Surface-Modified Electrodes for the Enhanced Electrochemical Detection of Selective Serotonin Reuptake Inhibitors (SSRIs).

Selective serotonin re-uptake inhibitors (SSRIs) are one of the most commonly prescribed classes of antidepressants used for the treatment of moderate to severe depressive disorder, personality disorders and various phobias. This class of antidepressants was created with improved margins of safety. However, genetic polymorphism may be responsible for the high variability in patients' responses to treatment, ranging from failure to delayed therapeutic responses to severe adverse effects of treatment. It is crucial that the appropriate amount of SSRI drugs is administered to ensure the optimum therapeutic efficacy and intervention to minimise severe and toxic effects in patients, which may be the result of accidental and deliberate cases of poisoning. Determining SSRI concentration in human fluids and the environment with high sensitivity, specificity and reproducibility, and at a low cost and real-time monitoring, is imperative. Electrochemical sensors with advanced functional materials have drawn the attention of researchers as a result of these advantages over conventional techniques. This review article aims to present functional materials such as polymers, carbon nanomaterials, metal nanomaterials as well as composites for surface modification of electrodes for sensitive detection and quantification of SSRIs, including fluoxetine, citalopram, paroxetine, fluvoxamine and sertraline. Sensor fabrication, sensor/analyte interactions, design rationale and properties of functional material and the electrocatalytic effect of the modified electrode on SSRI detection are discussed.

Impact of systemic dexamethasone dosage on docetaxel-induced oral mucositis in patients with breast cancer

Oral mucositis (OM) is a common adverse effect of docetaxel-containing treatment. This study aimed to assess whether dexamethasone (DEX) dose-dependently attenuates docetaxel-induced OM and dysgeusia. We retrospectively analyzed medical records of patients with breast cancer receiving docetaxel-containing regimens at Hokkaido University Hospital between June 2015 and June 2022. The patients were divided into low-dose and high-dose groups (DEX 4 or 8 mg/day on days 2–4, respectively), and incidence of OM and dysgeusia, and risk factor(s) for OM incidence were evaluated. The incidence of all-grade OM in the first cycle was 57.8% in the low-dose group and 19.2% in the high-dose group (P = 0.0002), which met our primary endpoint. The incidence of OM in all treatment cycles was also significantly lowered by DEX-dose increase (P = 0.01). In contrast, the incidence of dysgeusia was similar between the two groups in the first and all cycles (P = 0.50 and P = 0.28, respectively). These results were also confirmed in a propensity score-matched population. Multivariate logistic regression analysis also suggested that lower DEX dosage was a singular risk factor for all-grade OM incidence. In conclusion, our study suggests that DEX dose-dependently reduces the incidence of OM in docetaxel-containing regimens for breast cancer treatment.

Spin on adverse effects in abstracts of systematic reviews of orthodontic interventions: a cross-sectional study (part 2)

BackgroundIt is critical that abstracts of systematic reviews transparently report both the beneficial and adverse effects of interventions without misleading the readers. This cross-sectional study assessed whether adverse effects of interventions were reported or considered in abstracts of systematic reviews of orthodontic interventions and whether spin on adverse effects was identified when comparing the abstracts with what was sought and reported in these reviews.MethodsThis cross-sectional study (part 2 of 2) used the same sample of 98 systematic reviews orthodontic interventions as used in part 1. Eligible reviews were retrieved from the Cochrane Database of Systematic Reviews and the 5 leading orthodontic journals between August 1 2009 and July 31 2021. Prevalence proportions were sought for 3 outcomes as defined in the published protocol. Univariable logistic regression models were built to explore associations between the presence of spin in the abstract and a series of predictors. Odds ratios (OR) 95% confidence intervals (95% CI) were used to quantify the strength of associations and their precision.Results76.5% (75/98) of eligible reviews reported or considered (i.e., discussed, weighted etc.) potential adverse effects of orthodontic interventions in the abstract and the proportion of spin on adverse effects was 40.8% (40/98) in the abstract of these reviews. Misleading reporting was the predominant category of spin, i.e., 90% (36/40). Our explorative analyses found that compared to the Cochrane Database of Systematic Reviews all 5 orthodontic journals had similar odds of the presence of spin on adverse effects in abstracts of systematic reviews of orthodontic interventions. The odds of the presence of spin did not change over the sampled years (OR: 1.03, 95% CI: 0.9 to 1.16) and did not depend on the number of authors (OR: 0.93, 95% CI: 0.71 to 1.21), or on the type of orthodontic intervention (OR: 1.1, 95% CI: 0.45 to 2.67), or whether conflicts of interests were reported (OR: 0.74, 95% CI: 0.32 to 1.68).ConclusionEnd users of systematic reviews of orthodontic interventions have to be careful when interpreting results on adverse effects in the abstracts of these reviews, because they could be jeopardized by uncertainties such as not being reported and misleading reporting as a result of spin.

A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial)

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel.MethodsThis clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II–III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute’s Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss.DiscussionThis intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone.Trial registrationClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Dupilumab-associated mycosis fungoides: a cross-sectional study.

Treating atopic dermatitis (AD) with dupilumab, a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), may be associated with the progression of mycosis fungoides (MF).This study aimsto examine the associations between the length of dupilumab treatment, age and sex, and the onset of MF.An institutional data registry and literature search were used for a retrospective cross-sectional study. Only patients with a diagnosis of MF on dupilumab for the treatment of AD and eczematous dermatitis were included.The primary outcome was the length of dupilumab exposure, age, sex, and the onset of MF. Linear correlations (Pearson) and Cox regression analysis were used to assess the correlation and the risk.A total of 25 patients were included in this study. Five eligible patients were identified at our institution. In addition, a PubMed review identified an additional 20 patients. At the time of MF diagnosis, the median age was 58, with 42% female. Disease history was significant for adult-onset AD in most patients (n = 17, 65.4%) or recent flare of AD previously in remission (n = 3, 11.5%). All patients were diagnosed with MF, and one patient progressed to Sézary syndrome while on dupilumab, with an average duration of 13.5months of therapy prior to diagnosis. Tumor stage at diagnosis of MF was described in 19 of the cases and ranged from an early-stage disease (IA) to advanced disease (IV). Treatment strategies included narrow-band UVB therapy, topical corticosteroids, brentuximab, pralatrexate, and acitretin. Male gender, advanced-stage disease, and older age correlated significantly with the hazard of MF onset and a shorter time to onset during dupilumab treatment.Our results suggest a correlation between the duration of dupilumab treatment and the diagnosis of MF, the higher MF stage at diagnosis, and the shorter the duration of using dupilumab to MF onset. Furthermore, elderly male patients appeared to be more at risk as both male gender and older age correlated with a hazard of MF diagnosis. The results raise the question as to whether the patients had MF misdiagnosed as AD that was unmasked by dupilumab or if MF truly is an adverse effect of treatment with dupilumab. Close monitoring of these patients and further investigation of the relationship between dupilumab and MF can shed more light on this question .