Drug Ther Bull. 2023 Mar 7:dtb-2023-000012. doi: 10.1136/dtb.2023.000012. Online ahead of print.

ABSTRACT

Overview of: Shrestha S, Poudel A, Cardona M, et al Impact of deprescribing dual-purpose medications on patient-related outcomes for older adults near end-of-life: a systematic review and meta-analysis. Ther Adv Drug Saf 2021;12:1-16.

PMID:36882298 | DOI:10.1136/dtb.2023.000012

Drug Ther Bull. 2023 Mar 7:dtb-2023-000016. doi: 10.1136/dtb.2023.000016. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some of the key changes that have been made to BNF content.

PMID:36882297 | DOI:10.1136/dtb.2023.000016

Eur Arch Otorhinolaryngol. 2023 Mar 7. doi: 10.1007/s00405-023-07896-z. Online ahead of print.

ABSTRACT

PURPOSE: Disturbance of cochlear microcirculation is discussed as final common pathway of various inner ear diseases. Hyperfibrinogenemia causing increased plasma viscosity is a possible factor for a critical reduction of cochlear blood flow that might lead to sudden sensorineural hearing loss (SSHL). The aim was to determine the efficacy and safety of drug-induced defibrinogenation by ancrod for SSHL.

METHODS: Double-blind, randomized, placebo-controlled, multicenter, parallel group, phase II (proof-of-concept) study (planned enrollment: 99 patients). Patients received an infusion of ancrod or placebo (day 1) followed by subcutaneous administrations (day 2, 4, 6). Primary outcome was the change in pure tone audiogram air conduction average until day 8.

RESULTS: The study was terminated early due to slow recruiting (31 enrolled patients: 22 ancrod, 9 placebo). A significant improvement of hearing loss was registered in both groups (ancrod: - 14.3 dB ± 20.4 dB, - 39.9% ± 50.4%; placebo: - 22.3 dB ± 13.7 dB, - 59.1% ± 38.0%). A statistically significant group-difference was not detected (p = 0.374). Placebo response of 33.3% complete and 85.7% at least partial recovery was observed. Plasma fibrinogen levels were reduced significantly by ancrod (baseline: 325.2 mg/dL, day 2: 107.2 mg/dL). Ancrod was tolerated well, no adverse drug reaction was of severe intensity, no serious adverse events occurred.

CONCLUSION: Ancrod reduced fibrinogen levels that support its mechanism of action. The safety profile can be rated positively. Since the planned number of patients could not be enrolled, no efficacy conclusion can be drawn. The high rate of placebo response challenges clinical trials for SSHL and needs to be considered in future investigations. Trial registrations This study was registered in the EU Clinical Trials Register, EudraCT-No. 2012-000066-37 at 2012-07-02.

PMID:36881166 | DOI:10.1007/s00405-023-07896-z

JAMA. 2023 Mar 7;329(9):725-734. doi: 10.1001/jama.2023.1084.

ABSTRACT

IMPORTANCE: Olamkicept, a soluble gp130-Fc-fusion-protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 receptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression.

OBJECTIVE: To assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score ≥5, rectal bleeding score ≥1, endoscopy score ≥2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020.

INTERVENTIONS: Eligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks.

MAIN OUTCOMES AND MEASURES: The primary end point was clinical response at week 12 (defined as ≥3 and ≥30% decrease from baseline total Mayo score; range, 0-12 [worst] with ≥1 decrease and ≤1 in rectal bleeding [range, 0-3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12.

RESULTS: Ninety-one patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference vs placebo of 26.6% (90% CI, 6.2% to 47.1%; P = .03) for 600 mg and 8.3% (90% CI, -12.6% to 29.1%; P = .52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperuricemia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo.

CONCLUSIONS AND RELEVANCE: Among patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03235752.

PMID:36881032 | DOI:10.1001/jama.2023.1084

Clin Ophthalmol. 2023 Feb 27;17:657-665. doi: 10.2147/OPTH.S399590. eCollection 2023.

ABSTRACT

PURPOSE: To evaluate real-world experience using intravitreal brolucizumab (IVBr), alone or in combination with aflibercept, in eyes with neovascular age-related macular degeneration (nAMD) treated previously with other inhibitors of VEGF (anti-VEGF).

METHODS: This was a retrospective study of all eyes with nAMD treated with IVBr on a treat-and-extend protocol at a single center. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) at baseline and final visit, and drug-related adverse events were analyzed. Eyes with recurrent macular fluid on IVBr every 8 weeks were treated with a combination therapy alternating between IVBr and aflibercept every month.

RESULTS: Among 52 eyes (40 patients) on IVBr, all had been previously treated with other anti-VEGF therapy, with 73% having persistent macular fluid. After a mean follow-up of 46.2±27.4 weeks on IVBr, the mean treatment interval for intravitreal therapy increased to 8.8±2.1 weeks on IVBr from a baseline of 6.1±3.1 weeks (p<0.001). Macular fluid decreased and BCVA was stable/improved in 61.5% of eyes on IVBr. Ten eyes with increased macular fluid on IVBr monotherapy when extended to every 8 weeks were treated with combination therapy alternating between IVBr and aflibercept every 4 weeks. In these eyes, 80% had improved macular fluid on OCT and 70% stable or improved BCVA after a median follow-up of 53 weeks on combination therapy. Mild intraocular inflammation developed in four eyes, all occurring on IVBr monotherapy, and none had associated vision loss.

CONCLUSION: In the real world, IVBr used to treat eyes with nAMD previously treated with other anti-VEGF therapies appears to be well tolerated and associated with an improvement in macular fluid, stabilization of BCVA, and/or increase in intravitreal treatment interval. Combination therapy alternating between IVBr and aflibercept monthly appears to be well tolerated and can be considered for eyes with macular fluid on IVBr every 8 weeks.

PMID:36880020 | PMC:PMC9984903 | DOI:10.2147/OPTH.S399590

BMC Public Health. 2023 Mar 6;23(1):427. doi: 10.1186/s12889-023-15358-8.

ABSTRACT

BACKGROUND: Sleep apnea exerts adverse health effects due to inflammation and metabolic disruption. It is associated with metabolic diseases. However, the evidence of its relationship with depression is inconsistent. Therefore, this study aimed to investigate the relationship between sleep apnea and depressive symptoms in adults in the United States.

METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), wherein the data from 2005 to 2018 of 9,817 individuals were obtained. Sleep apnea was self-reported by the participants using a questionnaire on sleep disorders. The 9-item Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms. We implemented multivariable logistic regression and stratified analyses to assess the correlation between sleep apnea and depressive symptoms.

RESULTS: A total of 515 (6.6%) participants among 7,853 non-sleep apnea participants and 269 (13.7%) subjects among 1,964 sleep apnea participants had a depression score ≥ 10, they were deemed to have depressive symptoms. The multivariable regression model, showed that individuals with sleep apnea were 1.36-fold more likely to experience depressive symptoms when adjusted for potential covariates (odds ratios [OR] with 95% confidence intervals of 2.36 [1.71-3.25]), and a positive correlation between depressive symptoms and sleep apnea severity was found. The stratified analyses, revealed that sleep apnea was related to an increased incidence of depressive symptoms in most subgroups, except for those with coronary heart disease. Further, there was no interaction between sleep apnea and the covariates.

CONCLUSIONS: Adults with sleep apnea in the US have a relatively high prevalence of depressive symptoms. and the severity of sleep apnea positively correlated with the depressive symptoms.

PMID:36879197 | DOI:10.1186/s12889-023-15358-8

J Immunother Cancer. 2023 Mar;11(3):e005841. doi: 10.1136/jitc-2022-005841.

ABSTRACT

Immune checkpoint inhibitors (ICIs) are associated with a wide range of immune-related adverse events. As oncological indications for ICIs widen, their rare side effects become increasingly visible in clinical practice and impact therapy decisions.Here, we report a rare case of early-onset, mild cytokine release syndrome (CRS) in a patient who received ICIs for a metastasized renal cell carcinoma, which led to treatment discontinuation.We further provide a systematic review of the literature of CRS and related life-threatening side effects of ICI treatment, such as hemophagocytic lymphohistiocytosis (HLH). We searched Medline, Embase and the Web of Science Core Collection from inception to October 2021 for reports on CRS, cytokine storm, macrophage activation syndrome, HLH, and related hyperinflammatory disorders in patients with solid cancers receiving ICIs. We found n=1866 articles, which were assessed for eligibility independently by two examiners. Of those, n=49 articles reporting on n=189 individuals were eligible for review. We found that the median time from last infusion to the occurrence of CRS/HLH was approximately nine days, while the onset of symptoms varied from immediately after infusion to one month after treatment. Most patients were treated with either corticosteroids or the anti-interleukin 6 (IL-6) antibody tocilizumab, and although the majority of patients recovered, a few cases were fatal. Concomitant IL-6 and ICI treatment were reported as beneficial for both the antitumoral effect and for limiting side effects. Data from international pharmacovigilance databases underscored that ICI-related CRS and HLH are rare events, but we identified significant differences in reported frequencies, which might suggest substantial under-reporting.The results from this first systematic review of CRS/HLH due to ICI therapy highlight that life-threatening systemic inflammatory complications of ICIs are rare and might be associated with fatal outcome in approximately 10% of patients. Limited data support the use of IL-6 inhibitors in combination with ICIs to augment the antitumoral effect and reduce hyperinflammation.

PMID:36878533 | PMC:PMC9990684 | DOI:10.1136/jitc-2022-005841

Chin Med J (Engl). 2023 Jan 5;136(1):45-52. doi: 10.1097/CM9.0000000000002259.

ABSTRACT

BACKGROUND: Managing acute postoperative pain is challenging for anesthesiologists, surgeons, and patients, leading to adverse events despite making significant progress. Patient-controlled intravenous analgesia (PCIA) is a recommended solution, where oxycodone has depicted unique advantages in recent years. However, controversy still exists in clinical practice and this study aimed to compare two drugs in PCIA.

METHODS: We performed a literature search in PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases up to December 2020 to select specific randomized controlled trials (RCTs) comparing the efficacy of oxycodone with sufentanil in PCIA. The analgesic effect was the primary outcome and the secondary outcome included PCIA consumption, the Ramsay sedation scale, patients' satisfaction and side effects.

RESULTS: Fifteen RCTs were included in the meta-analysis. Compared with sufentanil, oxycodone showed lower Numerical Rating Scale scores (mean difference [MD] = -0.71, 95% confidence interval [CI]: -1.01 to -0.41; P < 0.001; I2 = 93%), demonstrated better relief from visceral pain (MD = -1.22, 95% CI: -1.58 to -0.85; P < 0.001; I2 = 90%), promoted a deeper sedative level as confirmed by the Ramsay Score (MD = 0.77, 95% CI: 0.35-1.19; P < 0.001; I2 = 97%), and resulted in fewer side effects (odds ratio [OR] = 0.46, 95% CI: 0.35-0.60; P < 0.001; I2 = 11%). There was no statistical difference in the degree of patients' satisfaction (OR = 1.13, 95% CI: 0.88-1.44; P = 0.33; I2 = 72%) and drug consumption (MD = -5.55, 95% CI: -14.18 to 3.08; P = 0.21; I2 = 93%).

CONCLUSION: Oxycodone improves postoperative analgesia and causes fewer adverse effects, and could be recommended for PCIA, especially after abdominal surgeries.

REGISTRATION: PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; CRD42021229973.

PMID:36878002 | DOI:10.1097/CM9.0000000000002259

J Drugs Dermatol. 2023 Mar 1;22(3):288-296. doi: 10.36849/JDD.7253.

ABSTRACT

Managing chronic conditions is an essential aspect of dermatologic care, especially regarding the resolution of inflammatory dermatologic disease and recovery of skin lesions. Short-term complications of healing include infection, edema, dehiscence, hematoma formation, and tissue necrosis. At the same time, longer-term sequelae may consist of scarring and scar widening, hypertrophic scars, keloids, and pigmentary changes. This review will focus on dermatologic complications of chronic wound healing in patients with Fitzpatrick skin type (FPS) IV-VI or skin of color (SOC), with an emphasis on hypertrophy/scarring and dyschromias. It will focus on current treatment protocols and the potential complications specific to patients with FPS IV-VI.&nbsp; Observations: There are multiple complications of wound healing that are more prevalent in SOC, including dyschromias and hypertrophic scarring. These complications are challenging to treat, and current protocols are not without complications and side effects that must be considered when offering therapy to patients with FPS IV-VI.&nbsp; Conclusions and Relevance: When treating pigmentary and scarring disorders in patients with skin types FPS IV-VI, it is essential to implement a stepwise approach to management that is conscious of the side effect profile of current interventions. J Drugs Dermatol. 2023;22(3):288-296. doi:10.36849/JDD.7253.

PMID:36877886 | DOI:10.36849/JDD.7253

Cochrane Database Syst Rev. 2023 Mar 6;3(3):CD012349. doi: 10.1002/14651858.CD012349.pub3.

ABSTRACT

BACKGROUND: Regularly transfused people with sickle cell disease (SCD) and people with thalassaemia are at risk of iron overload. Iron overload can lead to iron toxicity in vulnerable organs such as the heart, liver and endocrine glands, which can be prevented and treated with iron-chelating agents. The intensive demands and uncomfortable side effects of therapy can have a negative impact on daily activities and wellbeing, which may affect adherence.

OBJECTIVES: To identify and assess the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions) and interventions specific to different age groups, to improve adherence to iron chelation therapy compared to another listed intervention, or standard care in people with SCD or thalassaemia.

SEARCH METHODS: We searched CENTRAL (Cochrane Library), MEDLINE, PubMed, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Global Theses, Web of Science & Social Sciences Conference Proceedings Indexes and ongoing trial databases (13 December 2021). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (1 August 2022).

SELECTION CRITERIA: For trials comparing medications or medication changes, only randomised controlled trials (RCTs) were eligible for inclusion. For studies including psychological and psychosocial interventions, educational interventions, or multi-component interventions, non-randomised studies of interventions (NRSIs), controlled before-after studies, and interrupted time series studies with adherence as a primary outcome were also eligible for inclusion.

DATA COLLECTION AND ANALYSIS: For this update, two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE.

MAIN RESULTS: We included 19 RCTs and one NRSI published between 1997 and 2021. One trial assessed medication management, one assessed an education intervention (NRSI) and 18 RCTs were of medication interventions. Medications assessed were subcutaneous deferoxamine, and two oral chelating agents, deferiprone and deferasirox. We rated the certainty of evidence as very low to low across all outcomes identified in this review. Four trials measured quality of life (QoL) with validated instruments, but provided no analysable data and reported no difference in QoL. We identified nine comparisons of interest. 1. Deferiprone versus deferoxamine We are uncertain whether or not deferiprone affects adherence to iron chelation therapy (four RCTs, unpooled, very low-certainty evidence), all-cause mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.18 to 1.21; 3 RCTs, 376 participants; very low-certainty evidence), or serious adverse events (SAEs) (RR 1.43, 95% CI 0.83 to 2.46; 1 RCT, 228 participants; very low-certainty evidence). Adherence was reported as "good", "high" or "excellent" by all seven trials, though the data could not be analysed formally: adherence ranged from 69% to 95% (deferiprone, mean 86.6%), and 71% to 93% (deferoxamine, mean 78.8%), based on five trials (474 participants) only. 2. Deferasirox versus deferoxamine We are uncertain whether or not deferasirox affects adherence to iron chelation therapy (three RCTs, unpooled, very low-certainty evidence), although medication adherence was high in all trials. We are uncertain whether or not there is any difference between the drug therapies in serious adverse events (SAEs) (SCD or thalassaemia) or all-cause mortality (thalassaemia). 3. Deferiprone versus deferasirox We are uncertain if there is a difference between oral deferiprone and deferasirox based on a single trial in children (average age 9 to 10 years) with any hereditary haemoglobinopathy in adherence, SAEs and all-cause mortality. 4. Deferasirox film-coated tablet (FCT) versus deferasirox dispersible tablet (DT) One RCT compared deferasirox in different tablet forms. There may be a preference for FCTs, shown through a trend for greater adherence (RR 1.10, 95% CI 0.99 to 1.22; 1 RCT, 88 participants), although medication adherence was high in both groups (FCT 92.9%; DT 85.3%). We are uncertain if there is a benefit in chelation-related AEs with FCTs. We are uncertain if there is a difference in the incidence of SAEs, all-cause mortality or sustained adherence. 5. Deferiprone and deferoxamine combined versus deferiprone alone We are uncertain if there is a difference in adherence, though reporting was usually narrative as triallists report it was "excellent" in both groups (three RCTs, unpooled). We are uncertain if there is a difference in the incidence of SAEs and all-cause mortality. 6. Deferiprone and deferoxamine combined versus deferoxamine alone We are uncertain if there is a difference in adherence (four RCTs), SAEs (none reported in the trial period) and all-cause mortality (no deaths reported in the trial period). There was high adherence in all trials. 7. Deferiprone and deferoxamine combined versus deferiprone and deferasirox combined There may be a difference in favour of deferiprone and deferasirox (combined) in rates of adherence (RR 0.84, 95% CI 0.72 to 0.99) (one RCT), although it was high (> 80%) in both groups. We are uncertain if there is a difference in SAEs, and no deaths were reported in the trial, so we cannot draw conclusions based on these data (one RCT). 8. Medication management versus standard care We are uncertain if there is a difference in QoL (one RCT), and we could not assess adherence due to a lack of reporting in the control group. 9. Education versus standard care One quasi-experimental (NRSI) study could not be analysed due to the severe baseline confounding.

AUTHORS' CONCLUSIONS: The medication comparisons included in this review had higher than average adherence rates not accounted for by differences in medication administration or side effects, though often follow-up was not good (high dropout over longer trials), with adherence based on a per protocol analysis. Participants may have been selected based on higher adherence to trial medications at baseline. Also, within the clinical trial context, there is increased attention and involvement of clinicians, thus high adherence rates may be an artefact of trial participation. Real-world, pragmatic trials in community and clinic settings are needed that examine both confirmed or unconfirmed adherence strategies that may increase adherence to iron chelation therapy. Due to lack of evidence this review cannot comment on intervention strategies for different age groups.

PMID:36877640 | PMC:PMC9987409 | DOI:10.1002/14651858.CD012349.pub3

Cochrane Database Syst Rev. 2023 Mar 6;3(3):MR000055. doi: 10.1002/14651858.MR000055.pub2.

ABSTRACT

BACKGROUND: An estimated 60% of pharmacological randomised trials use placebo control interventions to blind (i.e. mask) participants. However, standard placebos do not control for perceptible non-therapeutic effects (i.e. side effects) of the experimental drug, which may unblind participants. Trials rarely use active placebo controls, which contain pharmacological compounds designed to mimic the non-therapeutic experimental drug effects in order to reduce the risk of unblinding. A relevant improvement in the estimated effects of active placebo compared with standard placebo would imply that trials with standard placebo may overestimate experimental drug effects.

OBJECTIVES: We aimed to estimate the difference in drug effects when an experimental drug is compared with an active placebo versus a standard placebo control intervention, and to explore causes for heterogeneity. In the context of a randomised trial, this difference in drug effects can be estimated by directly comparing the effect difference between the active placebo and standard placebo intervention.

SEARCH METHODS: We searched PubMed, CENTRAL, Embase, two other databases, and two trial registries up to October 2020. We also searched reference lists and citations and contacted trial authors.

SELECTION CRITERIA: We included randomised trials that compared an active placebo versus a standard placebo intervention. We considered trials both with and without a matching experimental drug arm.

DATA COLLECTION AND ANALYSIS: We extracted data, assessed risk of bias, scored active placebos for adequacy and risk of unintended therapeutic effect, and categorised active placebos as unpleasant, neutral, or pleasant. We requested individual participant data from the authors of four cross-over trials published after 1990 and one unpublished trial registered after 1990. Our primary inverse-variance, random-effects meta-analysis used standardised mean differences (SMDs) of active versus standard placebo for participant-reported outcomes at earliest post-treatment assessment. A negative SMD favoured the active placebo. We stratified analyses by trial type (clinical or preclinical) and supplemented with sensitivity and subgroup analyses and meta-regression. In secondary analyses, we investigated observer-reported outcomes, harms, attrition, and co-intervention outcomes.

MAIN RESULTS: We included 21 trials (1462 participants). We obtained individual participant data from four trials. Our primary analysis of participant-reported outcomes at earliest post-treatment assessment resulted in a pooled SMD of -0.08 (95% confidence interval (CI) -0.20 to 0.04; I2 = 31%; 14 trials), with no clear difference between clinical and preclinical trials. Individual participant data contributed 43% of the weight of this analysis. Two of seven sensitivity analyses found more pronounced and statistically significant differences; for example, in the five trials with low overall risk of bias, the pooled SMD was -0.24 (95% CI -0.34 to -0.13). The pooled SMD of observer-reported outcomes was similar to the primary analysis. The pooled odds ratio (OR) for harms was 3.08 (95% CI 1.56 to 6.07), and for attrition, 1.22 (95% CI 0.74 to 2.03). Co-intervention data were limited. Meta-regression found no statistically significant association with adequacy of the active placebo or risk of unintended therapeutic effect.

AUTHORS' CONCLUSIONS: We did not find a statistically significant difference between active and standard placebo control interventions in our primary analysis, but the result was imprecise and the CI compatible with a difference ranging from important to irrelevant. Furthermore, the result was not robust, because two sensitivity analyses produced a more pronounced and statistically significant difference. We suggest that trialists and users of information from trials carefully consider the type of placebo control intervention in trials with high risk of unblinding, such as those with pronounced non-therapeutic effects and participant-reported outcomes.

PMID:36877132 | PMC:PMC9989326 | DOI:10.1002/14651858.MR000055.pub2

Eur Rev Med Pharmacol Sci. 2023 Feb;27(4):1667-1680. doi: 10.26355/eurrev_202302_31410.

ABSTRACT

OBJECTIVE: Adverse drug reactions (ADRs) are widespread worldwide, and their intervention is critical to patient safety and healthcare quality. Pharmacists are essential in monitoring and reporting ADRs, directly influencing patient care. This study aimed to examine the prevalence of ADRs among pharmacists and their knowledge regarding ADRs, including the factors affecting ADR reporting.

SUBJECTS AND METHODS: From September 2021 to November 2021, a cross-sectional survey among pharmacists in the Asir area of Saudi Arabia was planned. This study involved contacting 97 pharmacists using a cluster sampling method. The study's goals were met using a 25-item self-administered questionnaire. Data analysis was done using SPSS version 25 (IBM Corp., Armonk, NY, USA).

RESULTS: Ninety-seven pharmacists (male 53.6% and female 46.4%) completed the survey. More than three-fourths of the participants (78.4%) know the ADR reporting system. The survey was completed by 97 pharmacists (male 53.6% and female 46.4%). More than three-quarters of the participants (78.4%) were aware of the ADR reporting system, and the majority (70.8%) were aware that it is done using an online system. Still, only 56.7% knew that the Saudi FDA is the regulatory agency collecting ADR data in Saudi Arabia. Furthermore, 73.2% cited stress in the workplace as a critical deterrent to reporting. Most respondents (76.3%) had an unfavorable attitude about reporting ADRs.

CONCLUSIONS: Pharmacists understand ADR reporting, but most lack the mentality to report the incidents. As a result, comprehensive and ongoing training for pharmacists is required to raise awareness of the need for ADR reporting.

PMID:36876701 | DOI:10.26355/eurrev_202302_31410

Eur Rev Med Pharmacol Sci. 2023 Feb;27(4):1322-1335. doi: 10.26355/eurrev_202302_31366.

ABSTRACT

OBJECTIVE: Myoclonus is one of the main complications of etomidate anesthesia, which would develop into serious consequences during surgery. The present analysis was performed to evaluate systematically the effect of propofol on preventing etomidate-induced myoclonus in adult patients.

MATERIALS AND METHODS: Systematic electronic literature search was performed in the databases PubMed, Cochrane Library, OVID, Wanfang and China National Knowledge Infrastructure (CNKI) from inception to May 20, 2021, without any language restrictions. All randomized controlled trials evaluating the efficacy of propofol on preventing etomidate-induced myoclonus were enrolled. The primary outcome included the incidence and degree of etomidate-induced myoclonus.

RESULTS: 1,420 patients (with 602 received etomidate anesthesia and 818 received propofol plus etomidate anesthesia) from 13 studies were eventually included. Whatever the intravenous propofol dose for anesthesia induction 0.8-2 mg/kg (RR:4.04, 95% CI [2.42,6.74] p<0.0001, I2=56.5%), or the dose of propofol for anesthesia induction 0.5-0.8 mg/kg (RR:3.26, 95% CI [2.03,5.22] p<0.0001, I2=0%), or the dose of propofol for anesthesia induction 0.25-0.5mg/kg (RR:1.68, 95% CI [1.1,2.56] p=0.0160, I2=0%), combination of propofol and etomidate could significantly decrease the occurrence of etomidate-related myoclonus (RR=2.99, 95% CI [2.40, 3.71] p<0.0001, I2=43.4%), compared with etomidate alone. In addition, propofol plus etomidate attenuated the incidence of mild (RR:3.40, 95% CI [1.7,6.82] p=0.0010, I2=54.3%), moderate (RR:5.4, 95% CI [3.01, 9.67] p<0.0001, I2=12.6%), severe (RR:4.15, 95% CI [2.11, 8.13] p<0.0001, I2=0%) of etomidate-induced myoclonus without adverse effects except for the increased incidence of pain on injection (RR:0.47, 95% CI [0.26, 0.83] p=0.0100, I2=41.5%) compared with etomidate alone.

CONCLUSIONS: The meta-analysis currently generates the evidence of combination of propofol with the dosage of 0.25-2 mg/kg and etomidate can alleviate the occurrence and severity of etomidate-induced myoclonus, with decreased incidence of postoperative nausea and vomiting (PONV) and comparative side effects of hemodynamic and respiratory depression of patients in comparison with etomidate alone.

PMID:36876671 | DOI:10.26355/eurrev_202302_31366

Front Endocrinol (Lausanne). 2023 Feb 16;14:1087614. doi: 10.3389/fendo.2023.1087614. eCollection 2023.

ABSTRACT

BACKGROUND AND AIMS: Some studies have reported that the topical forms with aminophylline as the active ingredient appear to be relatively effective on local fat burning while having no/minimal side effects. This systematic review accumulates all of the data on the local fat-burning potency of aminophylline topical formulation.

METHODS: Documents were retrieved from PubMed, Web of Science, and Scopus databases until Aug 2022. Data were extracted from clinical trials reporting the reduction in thigh or waist circumference as a result of using topical forms containing aminophylline. Screening of included studies was performed independently by two authors and the quality assessment of included studies was performed based on the Cochrane Collaboration's approach.

RESULTS: Of the 802 initial studies, 5 studies were included in the systematic review. Several concentrations of aminophylline were used in different studies. Most studies administred the topical formulation on participants' one thigh, and the other thigh was considered to be the control for comparing the fat reduction amount. Except for one study, all other studies reported that all participants lost more fat on the treated area than the control groups. The amount of fat reduction differed in studies regarding their different aminophylline concentrations and administration routines. In the case of side effects, except for some studies reporting skin rashes, other studies reported no significant side effects at all.

CONCLUSIONS: Aminophylline topical formulation offers a safe, effective, and much less invasive alternative to cosmetic surgery for localized fat reduction. It seems that the 0.5% concentration, administered five times a week for five weeks is the most potent concentration. However, more high-quality clinical trials are needed to verify this conclusion.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353578.

PMID:36875487 | PMC:PMC9978326 | DOI:10.3389/fendo.2023.1087614

Front Endocrinol (Lausanne). 2023 Feb 15;14:1044782. doi: 10.3389/fendo.2023.1044782. eCollection 2023.

ABSTRACT

OBJECTIVE: To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy (IMN).

METHODS: A total of 77 patients with IMN diagnosed in both our hospital and other hospitals were included in this study; the patients were divided into two groups: a treatment-naïve group (n = 19) and a refractory/relapsed group (n = 58). The clinical data of the patients, including urine examination, blood test, safety evaluation and efficacy evaluation results, were analysed retrospectively. The changes in clinical biochemical indexes and adverse reactions were compared between the two groups before and after treatment, and the clinical efficacy of rituximab (RTX) in the treatment of primary IMN and refractory recurrent membranous nephropathy was evaluated.

RESULTS: Of the 77 patients included in this study, the average age was 48 years, and there was a male-to-female ratio of 61:16. There were 19 cases in the initial treatment group and 58 cases in the refractory/relapse group. The 24-hour urine protein quantification, cholesterol, B cell count and M-type phospholipase A2 receptor (PLA2R) results in the 77 patients with IMN after treatment were all lower than those before treatment, and the differences were statistically significant (P < 0.05). Serum albumin was higher than before treatment, and the difference was statistically significant (P < 0.05). The total remission rate in the initial and refractory/relapsed treatment groups was 84.21% and 82.76%, respectively. There was no statistical difference in the total remission rate between the two groups (P > 0.05). During treatment, nine patients (11.69%) experienced infusion-related adverse reactions, which were relieved rapidly after symptomatic treatment. The anti-PLA2R antibody titre of the refractory/relapsed group was significantly negatively correlated with serum creatinine (r = -0.187, P = 0.045) and significantly correlated with 24-hour urine protein (r = -0.490, P < 0.001). There was a positive correlation and a significant negative correlation with serum albumin (r = -0.558, P < 0.001).

CONCLUSIONS: Regardless of whether RTX is used as an initial therapy or refractory/relapsed membranous nephropathy, most patients with IMN have complete or partial remission after RTX treatment, with mild adverse reactions.

PMID:36875477 | PMC:PMC9974647 | DOI:10.3389/fendo.2023.1044782

Front Immunol. 2023 Feb 16;14:1115083. doi: 10.3389/fimmu.2023.1115083. eCollection 2023.

ABSTRACT

Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP is mainly based on the systemic use of corticosteroids, but long-term use of corticosteroids results in a series of side effects. Type 2 inflammation is an immune response largely mediated by group 2 innate lymphoid cells, type 2 T helper cells, eosinophils, and inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13. Among patients with BP, the levels of immunoglobulin E and eosinophils are significantly increased in the peripheral blood and skin lesions, suggesting that the pathogenesis is tightly related to type 2 inflammation. To date, various targeted drugs have been developed to treat type 2 inflammatory diseases. In this review, we summarize the general process of type 2 inflammation, its role in the pathogenesis of BP and potential therapeutic targets and medications related to type 2 inflammation. The content of this review may contribute to the development of more effective drugs with fewer side effects for the treatment of BP.

PMID:36875098 | PMC:PMC9978795 | DOI:10.3389/fimmu.2023.1115083

World J Clin Cases. 2023 Feb 16;11(5):1115-1121. doi: 10.12998/wjcc.v11.i5.1115.

ABSTRACT

BACKGROUND: Combined small cell lung cancer (C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.

CASE SUMMARY: We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.

CONCLUSION: Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.

PMID:36874434 | PMC:PMC9979283 | DOI:10.12998/wjcc.v11.i5.1115

Curr Drug Saf. 2023 Mar 3. doi: 10.2174/1574886318666230303085538. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Adverse drug reactions (ADR) are considered any harmful and unintended side effects associated with the use of a drug at the usual therapeutic dose, in which skin is involved in most cases. Therefore, the availability of epidemiological information on reactions, reaction patterns, and their causative drugs can be helpful in timely diagnosis and necessary measures, such as caution in prescribing causative drugs to prevent these types of reactions.

METHODS: In this retrospective descriptive study, the archived files of patients with dermatoses due to ADR referred to Taleghani University Hospital, Urmia, Iran, during 2015-2020 were studied. Patterns and frequency of skin reactions, demographic data, and the frequency of chronic comorbidities were identified.

RESULTS: A total of 50 patients with drug-induced skin rash were found, of which 14 were male (28%) and 36 were female (72%). Skin rashes were most frequently found in patients aged 31-40 years. In 76% of patients, there was at least one chronic underlying disease. The most common reaction pattern was maculopapular rash (44%), and the most common causative drugs were antiepileptic drugs (34%) and antibiotics (22%). Mortality was found in 4 cases, which was due to antibiotics and antiepileptic drugs that caused toxic SJS/TEN and erythroderma. The hospital stays were highest in SJS and lowest in a maculopapular rash.

CONCLUSION: Knowledge about the epidemiology and the frequency of adverse drug reactions may be helpful in increasing the awareness of physicians for correct and rational drug prescriptions, which can reduce unnecessary hospital referrals and treatment costs.

PMID:36872363 | DOI:10.2174/1574886318666230303085538

J Med Case Rep. 2023 Mar 5;17(1):79. doi: 10.1186/s13256-023-03806-3.

ABSTRACT

BACKGROUND: Smartwatches offering electrocardiogram recordings advertise the benefits of supporting an active and healthy lifestyle. More often, medical professionals are faced with privately acquired electrocardiogram data of undetermined quality recorded by smartwatches. This is boasted by results and suggestions for medical benefits, based on industry-sponsored trials and potentially biased case reports. Yet potential risks and adverse effects have been widely overlooked.

CASE PRESENTATION: This case report describes an emergency consultation of a 27-year-old Swiss-German man lacking known previous medical conditions who developed an episode of anxiety and panic due to pain in the left chest prompted by over-interpretation of unremarkable electrocardiogram readings of his smartwatch. Fearing acute coronary syndrome, he presented at the emergency department. His smartwatch electrocardiograms, as well as a 12-lead electrocardiogram, appeared normal. After extensive calming and reassuring, as well as symptomatic therapy with paracetamol and lorazepam, the patient was discharged with no indications for further treatment.

CONCLUSIONS: This case demonstrates the potential risks of anxiety from nonprofessional electrocardiogram recordings by smartwatches. Medico-legal and practical aspects of electrocardiogram recordings by smartwatches need to be further considered. The case shows the potential side effects of pseudo-medical recommendations for the untrained consumer, and may add to the discussion on the ethics of how to evaluate smartwatch electrocardiogram data as a medical professional.

PMID:36871070 | PMC:PMC9985850 | DOI:10.1186/s13256-023-03806-3

J Transl Med. 2023 Mar 3;21(1):169. doi: 10.1186/s12967-023-03935-9.

ABSTRACT

BACKGROUND: Chemotherapy (CT) is central to the treatment of triple negative breast cancer (TNBC), but drug toxicity and resistance place strong restrictions on treatment regimes. Fasting sensitizes cancer cells to a range of chemotherapeutic agents and also ameliorates CT-associated adverse effects. However, the molecular mechanism(s) by which fasting, or short-term starvation (STS), improves the efficacy of CT is poorly characterized.

METHODS: The differential responses of breast cancer or near normal cell lines to combined STS and CT were assessed by cellular viability and integrity assays (Hoechst and PI staining, MTT or H2DCFDA staining, immunofluorescence), metabolic profiling (Seahorse analysis, metabolomics), gene expression (quantitative real-time PCR) and iRNA-mediated silencing. The clinical significance of the in vitro data was evaluated by bioinformatical integration of transcriptomic data from patient data bases: The Cancer Genome Atlas (TCGA), European Genome-phenome Archive (EGA), Gene Expression Omnibus (GEO) and a TNBC cohort. We further examined the translatability of our findings in vivo by establishing a murine syngeneic orthotopic mammary tumor-bearing model.

RESULTS: We provide mechanistic insights into how preconditioning with STS enhances the susceptibility of breast cancer cells to CT. We showed that combined STS and CT enhanced cell death and increased reactive oxygen species (ROS) levels, in association with higher levels of DNA damage and decreased mRNA levels for the NRF2 targets genes NQO1 and TXNRD1 in TNBC cells compared to near normal cells. ROS enhancement was associated with compromised mitochondrial respiration and changes in the metabolic profile, which have a significant clinical prognostic and predictive value. Furthermore, we validate the safety and efficacy of combined periodic hypocaloric diet and CT in a TNBC mouse model.

CONCLUSIONS: Our in vitro, in vivo and clinical findings provide a robust rationale for clinical trials on the therapeutic benefit of short-term caloric restriction as an adjuvant to CT in triple breast cancer treatment.

PMID:36869333 | PMC:PMC9983166 | DOI:10.1186/s12967-023-03935-9