Evidence-Based Medicine Reviews Research Articles

A systematic literature review and indirect treatment comparison of PARP inhibitors in combination with next-generation hormonal agents in BRCA-mutated metastatic castration-resistant prostate cancer.

e17029 Background: In the USA, several poly(ADP-ribose) polymerase inhibitors (PARPi) are approved in combination with next-generation hormonal agents (NHAs) for metastatic castration resistant-prostate cancer (mCRPC), including olaparib plus abiraterone acetate with prednisone/prednisolone (OLA+AA/P) and niraparib plus AA/P (NIRA+AA/P) for mCRPC with BRCA1 and/or BRCA2 mutations (BRCAm), and talazoparib plus enzalutamide (TALA+ENZ) for mCRPC with homologous recombination repair mutations, including BRCAm. All approvals were based on placebo (PBO)-controlled Phase III trials. To support clinical decision-making, we performed a systematic literature review and indirect treatment comparison (ITC) to assess the comparative efficacy and safety of regimens. Methods: Published clinical trials were identified by searching Embase, MEDLINE, Evidence-Based Medicine Reviews database, conferences and registries up to September 2023. Studies reporting radiographic progression-free survival (rPFS), overall survival (OS), and/or safety outcomes for mCRPC were included. The feasibility of performing anchored or unanchored ITCs using BRCAm subgroup data was assessed. Where feasible, Bayesian ITCs were performed using BRCAm subgroup hazard ratios (HRs) for investigator-assessed rPFS, blinded independent central review (BICR) rPFS, and OS. Safety ITCs were performed using overall study data and reported as risk differences (RD) for adverse events (AEs). Results: Thirty-nine studies were identified, of which three reported BRCAm-specific data, including PBO-controlled studies for OLA+AA/P, NIRA+AA/P, and TALA+ENZ. An anchored ITC was feasible for OLA+AA/P and NIRA+AA/P using PBO+AA/P as a common comparator. ITC results showed a significant improvement in rPFS and OS, and a numerical reduction in AE risk for OLA+AA/P vs NIRA+AA/P (Table). TALA+ENZ was excluded from the ITC as it was not possible to form a network with OLA+AA/P or NIRA+AA/P due to differences in NHA use (ENZ vs AA/P) in PBO-control arms, whilst data limitations prevented unanchored ITCs. Conclusions: In BRCAm mCRPC, ITC results suggest that OLA+AA/P has improved efficacy and a favorable safety profile vs NIRA+AA/P. Current evidence does not allow for a robust comparison of OLA+AA/P or NIRA+AA/P with TALA+ENZ in BRCAm mCRPC. [Table: see text]

A systematic literature review and indirect treatment comparison of PARP inhibitors in combination with next-generation hormonal agents in BRCA-mutated metastatic castration-resistant prostate cancer.

e17029 Background: In the USA, several poly(ADP-ribose) polymerase inhibitors (PARPi) are approved in combination with next-generation hormonal agents (NHAs) for metastatic castration resistant-prostate cancer (mCRPC), including olaparib plus abiraterone acetate with prednisone/prednisolone (OLA+AA/P) and niraparib plus AA/P (NIRA+AA/P) for mCRPC with BRCA1 and/or BRCA2 mutations (BRCAm), and talazoparib plus enzalutamide (TALA+ENZ) for mCRPC with homologous recombination repair mutations, including BRCAm. All approvals were based on placebo (PBO)-controlled Phase III trials. To support clinical decision-making, we performed a systematic literature review and indirect treatment comparison (ITC) to assess the comparative efficacy and safety of regimens. Methods: Published clinical trials were identified by searching Embase, MEDLINE, Evidence-Based Medicine Reviews database, conferences and registries up to September 2023. Studies reporting radiographic progression-free survival (rPFS), overall survival (OS), and/or safety outcomes for mCRPC were included. The feasibility of performing anchored or unanchored ITCs using BRCAm subgroup data was assessed. Where feasible, Bayesian ITCs were performed using BRCAm subgroup hazard ratios (HRs) for investigator-assessed rPFS, blinded independent central review (BICR) rPFS, and OS. Safety ITCs were performed using overall study data and reported as risk differences (RD) for adverse events (AEs). Results: Thirty-nine studies were identified, of which three reported BRCAm-specific data, including PBO-controlled studies for OLA+AA/P, NIRA+AA/P, and TALA+ENZ. An anchored ITC was feasible for OLA+AA/P and NIRA+AA/P using PBO+AA/P as a common comparator. ITC results showed a significant improvement in rPFS and OS, and a numerical reduction in AE risk for OLA+AA/P vs NIRA+AA/P (Table). TALA+ENZ was excluded from the ITC as it was not possible to form a network with OLA+AA/P or NIRA+AA/P due to differences in NHA use (ENZ vs AA/P) in PBO-control arms, whilst data limitations prevented unanchored ITCs. Conclusions: In BRCAm mCRPC, ITC results suggest that OLA+AA/P has improved efficacy and a favorable safety profile vs NIRA+AA/P. Current evidence does not allow for a robust comparison of OLA+AA/P or NIRA+AA/P with TALA+ENZ in BRCAm mCRPC. [Table: see text]

The Efficacy of Fat Grafting on Treating Post-Mastectomy Pain with and without Breast Reconstruction: A Systematic Review and Meta-Analysis.

Post-mastectomy pain syndrome (PMPS), characterized by persistent pain lasting at least three months following mastectomy, affects 20-50% of breast surgery patients, lacking effective treatment options. A review was conducted utilizing EMBASE, MEDLINE, and all evidence-based medicine reviews to evaluate the effect of fat grafting as a treatment option for PMPS from database inception to 29 April 2023 (PROSPERO ID: CRD42023422627). Nine studies and 812 patients in total were included in the review. The overall mean change in visual analog scale (VAS) was -3.6 in 285 patients following fat grafting and 0.5 in 147 control group patients. There was a significant reduction in VAS from baseline in the fat grafting group compared to the control group, n = 395, mean difference = -2.17 (95% CI, -2.95 to -1.39). This significant improvement was also noted in patients who underwent mastectomy without reconstruction. Common complications related to fat grafting include capsular contracture, seroma, hematoma, and infection. Surgeons should consider fat grafting as a treatment option for PMPS. However, future research is needed to substantiate this evidence and to identify timing, volume of fat grafting, and which patient cohort will benefit the most.

Insulin Use During Gestational and Pre-existing Diabetes in Pregnancy: A Systematic Review of Study Design.

Insulin is the first-line pharmacologic therapy for women with diabetes in pregnancy. However, conducting well-designed randomized clinical trials (RCTs) and achieving recommended glycemic targets remains a challenge for this unique population. This systematic literature review (SLR) aimed to understand the evidence for insulin use in pregnancy and the outcome metrics most often used to characterize its effect on glycemic, maternal and fetal outcomes in gestational diabetes mellitus (GDM) and in pregnant women with diabetes. An SLR was conducted using electronic databases in Medline, EMBASE via Ovid platform, evidence-based medicine reviews (2010-2020) and conference proceedings (2018-2019). Studies were included if they assessed the effect of insulin treatment on glycemic, maternal or fetal outcomes in women with diabetes in pregnancy. Studies on any type of diabetes other than gestational or pre-existing diabetes as well as non-human studies were excluded. In women diagnosed with GDM or pre-existing diabetes, most studies compared treatment of insulin with metformin (n = 35) followed by diet along with lifestyle intervention (n = 24) and glibenclamide (n = 12). Most studies reporting on glycemic outcomes compared insulin with metformin (n = 22) and glibenclamide (n = 4). Fasting blood glucose was the most reported clinical outcome of interest. Among the studies reporting maternal outcomes, method of delivery and delivery complications were most commonly reported. Large for gestational age, stillbirth and perinatal mortality were the most common fetal outcomes reported. This SLR included a total of 108 clinical trials and observational studies with diverse populations and treatment arms. Outcomes varied across the studies, and a lack of consistent outcome measures to manage diabetes in pregnant women was observed. This elucidates a need for global consensus on study design and standardized clinical, maternal and fetal outcomes metrics.

Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice. The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models. Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework. Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n=52), with the remaining studies being cost-effectiveness analyses (n=4) and a cost-minimization analysis (n=1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking. Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

Evidence for clinician underprescription of and patient non-adherence to guideline-recommended cardiovascular medications among adults with peripheral artery disease: protocol for a systematic review and meta-analysis

IntroductionInternational guidelines recommend that adults with peripheral artery disease (PAD) be prescribed antiplatelet, statin and antihypertensive medications. However, it is unclear how often people with PAD are underprescribed these drugs,...

A78 VALIDITY EVIDENCE FOR OBSERVATIONAL EUS COMPETENCY ASSESSMENT: A SYSTEMATIC REVIEW

Abstract Background Endoscopic ultrasound (EUS) encompasses a range of diagnostic and therapeutic procedures that require technical, cognitive, and non-technical skills. The implementation of competency-based frameworks in endoscopic education has emphasized trainee assessment based on predefined milestones, rather than procedure volume. Observational assessment tools with strong validity evidence are needed to achieve this goal. Aims To systematically identify and evaluate observational competency assessment tools employed in EUS using an established validity framework. The secondary aim is to evaluate the educational utility of assessment tools. Methods We searched three databases (MEDLINE, EMBASE, and Evidence-Based Medicine Reviews) and the grey literature from inception to May 2023. Messick’s unified framework was used to evaluate validity evidence based on content, response process, internal structure, relations to other variables, and consequences. Each domain was scored from 0 to 3 with a maximum score of 15 points. Educational utility was evaluated using the Accreditation Council for Graduate Medical Education Standards considering ease of use, ease of interpretation, resources required, and educational impact. Study quality was assessed using the Medical Education Research Quality Instrument. Results Our search identified 2081 records. We screened 44 full texts and included 5 observational EUS assessment tools from 10 studies. All 5 tools are formative assessments, with 4 employed in clinical settings and one in a simulated setting. All tools use Likert rating scales and are rater-based, with 2 having additional self-assessment components. Validity evidence scores ranged from 3 to 13, with the EUS Assessment Tool (EUSAT), Global Assessment of Performance and Skills in EUS (GAPS-EUS), and The EUS and ERCP Skills Assessment Tool (TEESAT) scoring highest, with 10, 11, and 13 points, respectively. Overall educational utility was high across studies given ease of tool use. The TEESAT had the strongest educational impact considering its influence on credentialing and competence thresholds. Study quality was high overall, with scores ranging from 9.5 to 12 (maximum 13.5 points). Inter-rater agreement for validity evidence and educational utility scoring was substantial (k=0.73, raw agreement 80%) and almost perfect (k=0.92, raw agreement 96%), respectively. Conclusions The EUSAT, GAPS-EUS, and TEESAT demonstrate the strongest validity evidence for observational competency assessment of EUS and are easy to implement in educational settings. Future work should investigate barriers to implementation and evaluate utility of these tools for summative assessment. EUS Observational Competency Assessment Tool Validity Evidence Scores Funding Agencies None

Efficacy and safety of autologous platelet-rich plasma for diabetic foot ulcers: a systematic review and meta-analysis

Objective: To investigate the efficacy and safety of autologous platelet-rich plasma (au-PRP) for diabetic foot ulcer (DFU) treatment. Method: We conducted database searches (MEDLINE, EMBASE, evidence-based medicine reviews: CENTRAL, PubMed, and Web of Science) and reference mining for randomised controlled trials from inception to 23 January 2022. Results were scrutinised, data were extracted and research quality was investigated by two independent authors. Primary outcome was the proportion of complete ulcer healing. Secondary outcomes included both the mean time to complete healing and the incidence of adverse events. Statistical analyses were performed in RevMan 5.4 (Cochrane, UK). Kaplan–Meier curves for time to complete healing were pooled in R software (version 4.1.2) (R Foundation, Austria). Results: Of the 231 records identified, 17 studies with a total of 1303 participants (649 randomised to the au-PRP group and 654 to a standard of care (SOC) group) met the eligibility criteria and were included in our study. Compared with SOC, au-PRP appeared to promote the complete healing rate (odds ratio (OR): 2.11; 95% Confidence Interval: 1.55–2.86). Au-PRP also appeared to significantly shorten complete healing time (mean duration: –19.04 days; 95%CI: –20.46––17.61]). There was no significant difference on adverse events. Results were robust on sensitivity analyses. Conclusion: Based on the findings of this review and meta-analysis, Au-PRP is an effective and safe adjuvant therapy for DFUs.

Have interventions aimed at assisting general practitioners in facilitating earlier diagnosis of type 1 diabetes in children been successful? A systematic review protocol

BackgroundEarly diagnosis of type 1 diabetes in children is critical to prevent deterioration to diabetic ketoacidosis (DKA), a state where the body’s insulin levels are critically low resulting in the...

OGC P20 A Systematic Mapping Review of Core Outcome Reporting in Surgical Research for Oesophageal Cancer

Abstract Background The UK has one of the highest rates of oesophageal adenocarcinoma worldwide. Surgical resection, with peri-operative chemotherapy, is the cornerstone of curative treatment. The evidence base for which surgical approach is best (including open, hybrid, totally laparoscopic/thoracoscopic, and robotic surgery) is negatively affected by heterogeneous reporting of outcomes. This study examines the degree to which outcomes deemed critically important to patients and healthcare professionals (a core outcome set - COS) are reported by studies in this field. Methods We undertook a mapping review of prospective cohort studies, randomized controlled trials (RCTs), and published protocols in the field of oesophageal cancer surgery. Evidence Based Medicine Reviews, MEDLINE, EMBASE, and CINAHL were searched for relevant studies conducted over a 10-year period (2011-2021). We mapped the reporting of 10 core outcomes during this period as described by a COS for oesophagectomy trials (overall survival; in-hospital mortality; inoperability; the need for additional intervention; respiratory complications; conduit necrosis and anastomotic leak; severe nutritional problems; the ability to eat and drink; problems with acid indigestion or heartburn and overall quality of life). Results Initial searches identified 8944 potentially eligible records, which, after exclusion of duplicates, abstract screening and full paper reviews, yielded 57 eligible studies that recruited 10,561 patients (36 prospective cohort studies, 16 RCT’s and 5 published protocols). No study reported all core outcomes. The median number of outcomes reported was 4 (IQR 3). ‘In-hospital mortality’ (86%), ‘conduit necrosis/leak’ (81%) and ‘respiratory complications’ (79%) were reported by most studies. ‘Quality of life’ (26%), reflux symptoms’ (21%) and 'severe nutritional effects' (19%) were rarely reported alongside ‘need for reintervention’ (16%). No improvement in reporting rates was seen during the study period. Conclusions The reporting of core outcomes in surgical research for oesophageal cancer does not adequately reflect the priorities of patients and healthcare professionals. Further work is therefore needed to significantly improve the reporting of these core outcomes and increase the methodological quality of studies in this field. The results from this study suggest that there is a need for further high-quality prospective studies and RCTs which encompass the reporting of core outcomes.

Is post-traumatic stress disorder a risk factor for development of opioid use disorder among individuals with chronic non-cancer pain? A systematic review.

There is emerging evidence that posttraumatic-stress disorder may have mediating effects in development of chronic-non-cancer-pain and opioid-use-disorder independently, but its impact on the development of opioid-use-disorder in people with chronic-non-cancer pain is still unclear. (i) Estimate the risk of opioid-use-disorder among individuals with chronic-non-cancer-pain and posttraumatic-stress disorder, relative to those with chronic-non-cancer-pain only, and (ii) identify potential correlates of opioid-use-disorder among people with chronic-non-cancer-pain and posttraumatic-stress disorder. This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Longitudinal, epidemiological, cohort, follow-up, retrospective, prospective and cross-sectional studies reporting measures of variance on the likelihood of developing opioid-use-disorder with posttraumatic-stress disorder among individuals with chronic-non-cancer-pain were identified from six-electronic databases (Medline, Embase, Evidence-based Medicine reviews, PsycINFO, Scopus and Web of Science) until December 2022. Three out of the four studies, which met the selection criteria for this analysis reported statistically significant positive association between risk of developing opioid-use-disorder with posttraumatic-stress disorder among chronic-non-cancer-pain cohort (unadjusted Relative-Risk range: 1.51-5.27) but this association was not evident in the fourth study (adjusted Relative-Risk: 0.96; statistically non-significant), when adjusted for sociodemographic variables. The increased risk was noted particularly with females and chronic musculoskeletal pain conditions. Posttraumatic-stress disorder can increase the risk of development of opioid-use-disorder among people with chronic-non-cancer-pain and a better understanding of this relationship will help to predict and prevent the development of opioid-use-disorder and may also help in reducing the disability and burden associated with chronic-non-cancer-pain. This review quantifies the risk of developing opioid-use-disorder in the context of posttraumatic-stress disorder among individuals with chronic-non-cancer-pain. Awareness and subsequent practice change will reduce the increasing global burden associated with the chronic-non-cancer-pain.

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis.

Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

#5534 HIFS AND BUTS: A NETWORK META-ANALYSIS OF HIF-PH INHIBITORS AND ESAS IN NDD-CKD PATIENTS WITH ANEMIA COMPARING THEIR SAFETY AND EFFICACY

Abstract Background and Aims Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of oral medicines for the management of anemia in CKD patients. These agents are found to be efficacious in the management of renal anemia, however safety is still under scrutiny. While, ESAs (Erythropoietin stimulating agents) are available since long with a well-established clinical profile. This network meta-analysis aimed to compare the safety and efficacy of HIF-PHI vs ESA in CKD patients with anemia not undergoing dialysis. Method An electronic database search was carried out in EBM (Evidence Based Medicine) Reviews, Cochrane Library and PubMed from inception to July 2022 for phase III clinical trials comparing six different HIF-PHIs and ESA for treating anemia in non-dialysis-dependent (NDD) CKD patients. The outcomes included the serious adverse events (SAEs) and change in hemoglobin (Hb) levels. Results Total 163 records were identified out of which 6 studies involving a total of 6847 patients were eligible for analysis. Compared to ESA, all HIF-PHIs increased risk for SAEs (daprodustat of RR, 1.21[95% CI, 0.825–1.77]; desidustat, 1.38[95% CI, 0.695–2.76]; enarodustat, 1.29[95% CI, 0.568–3.02]; molidustat, 1.02[95% CI, 0.585–1.74]; roxadustat, 1.29[95% CI, 0.674–2.57] and vadadustat, 1.01[95% CI, 0.693–1.47]) although these differences were statistically non-significant. When change in Hb was analyzed, there was no statistically significant difference between the two groups. The mean difference in change in HB with various HIFs as compared to ESA were: daprodustat (MD: 0.0796, 95% CI −0.676–0.838), desidustat (MD: 0.120, 95% CI: −0.626–0.883), enarodustat (MD: -0.600, 95% CI: −1.36–0.157), molidustat (MD: -0.309, 95% CI: −1.07–0.449), roxadustat (MD: -0.0702, 95% CI: −0.831–0.692) and vadadustat (MD: -0.0402, 95% CI: −0.802–0.720). Conclusion In terms of safety, HIF PHIs were associated with more SAEs compared to ESA although these differences are not statistically significant. Comparing efficacy, HIF-PHIs and ESA both effectively increase Hb level in NDD-CKD patients without any significant difference. Results of our network meta-analysis suggest the need for larger and long-term studies comparing HIF-PHIs with ESAs to have better understanding of their comparative efficacy and safety profiles.

Visual skills essential for rugby.

Keen vision is one of the most important qualities required of athletes. It enables players to perform sports-related drills and apply decision-making skills. To accurately measure the visual ability of athletes, it is important to first identify the variety of visual skills involved in the particular sport. The objectives of this novel review are to identify the most important visual skills required for rugby, and to create a reference point for further studies to include visual skills essential to rugby players. We conducted an electronic search with various combinations of relevant keywords using the following databases: Sport Discuss, Ovid's Evidence-Based Medicine Reviews, PubMed/MEDLINE, Current Contents, Science Direct, the National Research Council's Canada Institute for Scientific and Technical Information, Cochrane Database of Systematic Reviews, Google Scholar, and international electronic catalogues to assess the scientific literature related to the visual skills required for rugby. Only the records published in English were included. We extracted data on the relationship between vision and match performance, the defined problem or purpose of the study, and the inclusion of theoretical definitions of tactical behaviors. Our search yielded 80 records, 51 of which fulfilled the inclusion criteria. The most important visual skills in rugby are classified based on whether they meet the requirements for visual hardware or visual software skills. Visual hardware skills include visual acuity, depth perception, fusion flexibility, and contrast sensitivity; visual software skills include eye tracking, hand-eye coordination, eye focusing, peripheral vision, speed and span of recognition, visual response time, and visual memory. Rugby players must use both visual hardware and software skills to reliably observe their teammates' positions, understand their opponents' actions and tactics, handle the ball, analyze the immediate circumstances, and anticipate what will occur. Further studies are needed to verify the significance of each visual skill in actual competition to determine a relationship between vision and the results of a championship.

Diclofenac Sodium for Fever Control in Neurocritical Care: A Systematic Review.

Fever is extremely common in neurocritical care patients and is independently associated with a worse outcome. Non-steroidal anti-inflammatory drugs (NSAIDs) lower the hypothalamic set point temperature through the inhibition of prostaglandin E2 synthesis, and they constitute a second line of pharmacological treatment for temperature control. This systematic review aims to evaluate the effectiveness of DCF in reducing body temperature and its effects on brain parameters. A comprehensive search of several databases was run in November 2022 in Ovid EBM (Evidence Based Medicine) Reviews, Cochrane library, Ovid Medline and Scopus (1980 onward). The outcome of interest included DCF control of body temperature and its impact on cerebral parameters. A total of 113 titles were identified as potentially relevant. Six articles met eligible criteria and were reviewed. DCF induce a reduction in body temperature (MD, 1.10 [0.72, 1.49], p < 0.00001), a slight decrease in ICP (MD, 2.22 [-0.25, 4.68] IC 95%; p < 0.08) as well as in CPP and MAP (MD, 5.58 [0.43, 10.74] IC 95%; p < 0.03). The significant heterogeneity and possibility of publication bias reduces the strength of the available evidence. Diclofenac sodium is effective in reducing body temperature in patients with brain injury, but data in the literature are scarce and further studies are needed to evaluate the benefits of DCF.

Evaluation of health utility in trial-based cost–utility analyses for major cardiovascular disease: protocol for a systematic review

IntroductionThe global incidence of cardiovascular disease (CVD) is high, and the medical costs associated with its management have been increasing. Cost–utility analyses (CUAs) are essential for understanding the value of...

Efficacy of Strategies Intended to Prevent Surgical Site Infection After Lower Limb Revascularization Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The objective of this study is to evaluate the efficacy of strategies intended to prevent surgical site infection (SSI) after lower limb revascularization surgery. SSIs are common, costly complications of lower limb revascularization surgery associated with significant morbidity and mortality. We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (inception to April 28, 2022). Two investigators independently screened abstracts and full-text articles, extracted data, and assessed the risk of bias. We included randomized controlled trials (RCTs) that evaluated strategies intended to prevent SSI after lower limb revascularization surgery for peripheral artery disease. We used random-effects models to pool data and GRADE to assess certainty. Among 6258 identified citations, we included 26 RCTs (n=4752 patients) that evaluated 12 strategies to prevent SSI. Preincision antibiotics [risk ratio (RR)=0.25; 95% CI, 0.11-0.57; n=4 studies; I2 statistic=7.1%; high certainty] and incisional negative-pressure wound therapy (iNPWT) (RR=0.54; 95% CI, 0.38-0.78; n=5 studies; I2 statistic=7.2%; high certainty) reduced pooled risk of early (≤30 days) SSI. iNPWT also reduced the risk of longer-term (>30 days) SSI (pooled-RR=0.44; 95% CI, 0.26-0.73; n=2 studies; I2 =0%; low certainty). Strategies with uncertain effects on risk of SSI included preincision ultrasound vein mapping (RR=0.58; 95% CI, 0.33-1.01; n=1 study); transverse groin incisions (RR=0.33; 95% CI, 0.097-1.15; n=1 study), antibiotic-bonded prosthetic bypass grafts (RR=0.74; 95% CI, 0.44-1.25; n=1 study; n=257 patients), and postoperative oxygen administration (RR=0.66; 95% CI, 0.42-1.03; n=1 study) (low certainty for all). Preincision antibiotics and iNPWT reduce the risk of early SSI after lower limb revascularization surgery. Confirmatory trials are required to determine whether other promising strategies also reduce SSI risk.

Expansion sphincter pharyngoplasty in OSA: a 15year review.

A 15year review of the outcomes and success rates of the Expansion Sphincter Pharyngoplasty (ESP) in the treatment of patients with obstructive sleep apnea (OSA). A systemic review with two independent searches of MEDLINE, Google Scholar, Cochrane Library and Evidence-Based Medicine Reviews to identify publications relevant to OSA and Expansion Pharyngoplasty. All relevant studies published before 31 December 2021 were included. Sixteen studies were included in this strict systematic review with a total of 747 patients who had the ESP procedure were included. The mean age was 41.3years, mean BMI 28.2, the mean pre-op AHI was 32.3 and post-op AHI was 10.0 (p < 0.05), the mean pre-op ESS was 11.4, had reduced to post-op 5.3 (p < 0.05), and the mean pre-op snore VAS decreased from 8.7 to 2.9 (p < 0.05), with a mean follow-up time of 9.5months. The overall pooled success rate for all the 747 patients was 80.0%. There were no significant reported complications noted in these studies. After 15years of presence, the expansion sphincter pharyngoplasty has shown to be reliably effective in the management of patients with OSA.

Effect of Pharmacotherapy for Overactive Bladder on the Incidence of and Factors Related to Urinary Tract Infection: A Systematic Review and Meta-analysis.

The aim of this meta-analysis was to investigate the effect of pharmacotherapy for overactive bladder on the pathogenesis of urinary tract infection. A comprehensive search was performed in MEDLINE and the Cochrane Library using terms for overactive bladder, antimuscarinic agents, and beta 3-adrenoceptor agonists. The primary end point was the emergence of urinary tract infection after pharmacotherapy for overactive bladder. The secondary end point was the emergence of urinary retention, dysuria, and/or increased residual urine volume after overactive bladder treatment. Meta-analyses were conducted using random-effects models. A total of 35,939 patients in 33 trials (29 trials of antimuscarinic agents vs placebo, and 9 trials of beta 3-adrenoceptor agonists vs placebo) that included patients with overactive bladder were identified. At 1-3 months after treatment, the incidence of urinary tract infections was statistically significantly higher in the patients treated with antimuscarinic agents (RR: 1.23, 95% CI: 1.04, 1.45; P = .013) than in the placebo control group. The incidence of urinary tract infections was not increased in the patients treated with beta 3-adrenoceptor agonists (RR: 1.04, 95% CI: 0.76, 1.42; P = .796). Antimuscarinic agents also statistically significantly increased the risks of urinary retention, dysuria, and/or increased residual urine volume (RR: 2.88, 95% CI: 1.79, 4.63; P < .001), whereas beta 3-adrenoceptor agonists did not (RR: 1.26, 95% CI: 0.38, 4.14; P = .708). This meta-analysis showed that antimuscarinic agents statistically significantly increased the incidences of urinary tract infection and lower urinary tract symptoms and dysfunction, but beta 3-adrenoceptor agonists did not. To prevent urinary tract infection emergence, beta 3-adrenoceptor agonists might be safer than antimuscarinic agents.

Music, movement and mood in Parkinson’s: A transdisciplinary study to develop a new protocol to measure functional mobility in people with Parkinson’s by integrating motion capture with a pressure sensitive gait mat

Background&#x0D; Parkinson’s disease (PD) is a neurodegenerative brain disorder associated with early-onset functional motor impairments (Rana et al., 2012). There are several assessment scales for the evaluation of PD, but many motor measurement protocols lack reference to the qualitative assessment of functional mobility in everyday life (Opara et al., 2017). Moreover, previous studies have shown that pharmaceutical treatments in combination with physical therapy play an important role in improving motor symptoms, but the benefits do not seem to extend to mental well-being (Fox et al., 2018). Growing evidence suggest that an interdisciplinary approach by integrating musical activity with exercises may have the potential to improve both functional mobility and psychological wellbeing (Barnish &amp; Barran, 2020).&#x0D; Methods&#x0D; The first phase of this mixed methods study includes a Patient and Public Involvement (PPI) consultation process (workshops and interviews; Rose et al., 2022) to develop a context-appropriate new group-based intervention program for and with PwP and health professionals. The focus will lie on music activity and the use music imagery to develop individual jukeboxes of musical cues to combat motor symptoms such as rigidity and freeze of gait. To evaluate the efficacy and the generalisability of the program, a 12-week within-subject repeated measures controlled trial will be conducted in Switzerland and the UK. An accurate and reliable quantitative measurement protocol will be developed to enable assessment of disease progression, and evaluation of interventions alongside qualitative observations of mobility in PwP. Moreover, we aim to provide fine-grained assessment of clinical measures (such as the Timed Up and Go) using an integrated motion capture (MoCap) and gait mat analysis system.&#x0D; Expected Outcomes and Perspectives&#x0D; This project lays the foundation for the development of non-pharmaceutical and low-cost intervention programs. Our PPI approach will provide better individualised and targeted prevention strategies to counteract the increasing financial and personal burden of PD worldwide. A unique aspect of the study is to develop a new quantitative functional mobility measurement protocol to assess PwP over time. This research approach will contribute to our understanding of functional mobility symptoms and the use of music in PD to reduce symptom severity and improve quality of life.&#x0D; References&#x0D; Barnish, M. S., &amp; Barran, S. M. (2020). A systematic review of active group-based dance, singing, music therapy and theatrical interventions for quality of life, functional communication, speech, motor function and cognitive status in people with Parkinson’s disease. BMC Neurology, 20(1), Article 371. https://doi.org/10.1186/s12883-020-01938-3&#x0D; Fox, S. H., Katzenschlager, R., Lim, S. Y., Barton, B., de Bie, R. M. A., Seppi, K., Coelho, M., &amp; Sampaio, C. (2018). International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson’s disease. Movement Disorders, 33(8),1248-1266. https://doi.org/10.1002/mds.27372&#x0D; Opara, J., Małecki, A., Małecka, E., &amp; Socha, T. (2017). Motor assessment in Parkinson’s disease. Annals of Agricultural and Environment Medicine, 24(3), 411-415. https://doi.org/10.5604/12321966.1232774&#x0D; Rana, A. Q., Siddiqui, I., &amp; Yousuf, M. S. (2012). Challenges in diagnosis of young onset Parkinson’s disease. Journal of the Neurological Sciences, 323(1-2), 113-116. https://doi.org/10.1016/j.jns.2012.08.029&#x0D; Rose, D. C., Poliakoff, E., Hadley, R., Guérin, S. M. R., Phillips, M., &amp; Young, W. R. (2022) Levelling the playing field: The role of workshops to explore how people with Parkinson’s use music for mood and movement management as part of a patient and public involvement strategy. Frontiers in Rehabilitation Sciences, 3, Article 873216. https://doi.org/10.3389/fresc.2022.873216