Low-grade Evidence Research Articles

Preventing deformities in paediatric cerebral palsy in poorly-resourced areas: A scoping review.

Managing children with cerebral palsy (CP) in poorly-resourced contexts, especially those with greater functional limitations, is challenging. Unmitigated orthopaedic complications can further restrict already compromised functional capacity. Where rehabilitation skills and knowledge are scarce, primary healthcare worker- and caregiver-implemented routines are warranted. The essential elements of a home-based routine to mitigate musculoskeletal (MSK) complications in children with severe CP in resource-limited settings (RLSs) have not been determined. To summarise the evidence for programmes and interventions that mitigate MSK complications in children with severe CP and make recommendations for a programme suited to RLSs. Scientific databases and professional websites were searched for studies and reports describing guidelines, interventions or programmes for children aged 0-18 years with severe, partially- or non-ambulant CP, that included aims for the prevention of MSK complications. Articles reporting on surgical, pharmacological and advanced or expensive technological interventions were excluded. A total of 57 studies or reports were included in the review. Low-grade evidence exists for 24-hour postural management (24-h PM), supported standing, sustained stretching and splinting to mitigate MSK complications in children with CP. Caregiver training and support, and integration of the programme into daily routines were identified as important components for successful implementation. Clinical guidelines and evidence that support caregiver-delivered interventions to reduce MSK complications in children with severe CP are limited, and only weak recommendations can be made. There is a need for context-specific, home-based intervention programmes to prevent MSK complications in children with CP in RLSs.

Impact of Medical Trainees on Efficiency and Productivity in the Emergency Department: Systematic Review and Narrative Synthesis.

Effective medical education must balance clinical service demands for institutions and learning needs of trainees. The question of whether these are competing demands or can serve complementary roles has profound impacts on graduate medical education, ranging from funding decisions to the willingness of community-based hospitals and physicians to include learners at their clinical sites. Our objective in this article was to systematically review the evidence on the impact of medical trainees on productivity and efficiency in the emergency department (ED). We queried PubMed, Embase, Scopus, and Web of Science from earliest available dates to March 2023. We identified all studies evaluating the impact of medical students and/or residents in the ED on commonly used productivity and efficiency metrics. Only studies in EDs in the United States were included. No additional filters were used. We assessed the risk of bias of included studies using the Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) tool. Certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Study findings were combined in a narrative synthesis and reported according to PRISMA guidelines. The literature search yielded 3,390 unique articles for abstract screening. Eighty-one abstracts were identified as relevant to our PICO question (population, intervention, control, and outcomes), 76 of which had retrievable full-text articles and the themes of which were discussed in a narrative synthesis. We selected 13 of the full-text articles for final inclusion in a systematic review. Studies were roughly split between observational (6) and quasi-experimental (7) designs. The majority of studies (11) were single-site studies. Only two studies could be graded as low risk of bias per the ROBINS-I tool. Low-GRADE evidence suggests that students and residents decrease ED efficiency by a statistically small effect size of debatable clinical importance. Residents provide a moderate boost to ED productivity. Students do not produce a statistically or clinically significant impact on ED productivity. Residents increase emergency department relative value units revenue by $26.30 an hour, while students have no impact. Both types of learners decrease efficiency.

Core training for pain management and functional improvement in patients with patellofemoral pain syndrome: a systematic review and meta-analysis.

To investigate the effects of core strengthening exercises on pain, mobility, and lower extremity muscle strength in patients with Patellofemoral Pain Syndrome (PFP). Six databases were searched from inception until August 11, 2023. Pain, function and muscle strength related outcomes were extracted and the quality of the studies was assessed using the PEDro scale and the level of evidence was assessed using the GRADE. Nineteen studies involving 1138 patients were included. Very low-grade evidence supported the short-term pain-relieving effect of core training (SMD = -0.60 95% CI [-0.95, -0.25]), high-grade evidence supported the short-term functional improvement effects of core training (WMD = 3.61 95% CI [1.44, 5.78]), which was similarly significant within 3-12 months of follow-up. The results of the subgroup analyses suggested that hip-knee training was most advantageous in relieving pain and enhancing motor function. Although training that includes trunk core is clearly superior to knee strengthening alone, the effectiveness of hip-knee training, which is also a core training program for pain and function, is more pronounced. The available evidence supports that hip-knee training is the most valuable treatment option for patients with PFP.

Pediatric Odontogenic Sinusitis: A Systematic Review.

Background: Pediatric odontogenic sinusitis (PODS) is a rare condition with limited research on its clinical features, diagnostic criteria, and treatment options. The current guidelines on pediatric rhinosinusitis do not mention a possible dental origin of the disease. This systematic review aims to summarize and analyze the existing literature on PODS, focusing on epidemiology, etiology, diagnostic tools, complications, treatment options, and outcomes. Methods: A systematic review was conducted following PRISMA reporting guidelines. Electronic searches were performed in multiple databases using keywords related to PODS and therapeutic strategies. Original articles reporting data on treatment outcomes for PODS were included. Results: The review highlighted the scarcity of high-quality evidence on PODS. The literature mainly consists of case reports and low-grade evidence studies. Limited data on the epidemiology, etiology, diagnostic tools, complications, and treatment outcomes of PODS in children are available. Conclusions: Further research is needed to better understand the clinical features, diagnosis, and treatment of PODS in pediatric patients. High-quality studies are required to establish evidence-based guidelines for the management of this condition, especially given the apparently high rate of complications when compared to adult ODS.

Management & surveillance of rectal neuroendocrine tumours: a single-centre retrospective analysis.

Rectal neuroendocrine tumours (rNETs) are rare but are increasing in incidence. Current management and surveillance recommendations are based on low-grade evidence. Follow-up practices are often inconsistent and costly. This retrospective study analyses a single-centre's experience with rNETs to assess incidence, management practices, outcomes, and guideline adherence. This is a single-centre retrospective study from Queensland Australia, spanning from 2012 to 2023. Twenty-eight rNET cases met inclusion criteria. Examined parameters included incidence, management, outcomes and adherence to European Neuroendocrine Tumour Society (ENETS) guidelines. R1 resection rate was analysed for associations with resection technique and lesion recognition and recurrence rate was assessed in all patients. This study shows an increasing incidence of rNETs during the study period, reflecting a global trend. R1 resection rate at initial endoscopy was 75%. There was a general lack of advanced endoscopic techniques utilized and poor lesion recognition, however a statistically significant correlation was not established between these factors and an R1 result (P < 0.05). Most patients with an R1 result had subsequent re-resection to render the result R0, however five patients (33%) underwent surveillance with no reports of recurrence on follow-up. Overall, follow-up practices in our cohort were inconsistent and did not adhere to guidelines. rNETs are increasing in incidence, emphasizing the need for standardized management and surveillance. Further training is required for rNET recognition and advanced endoscopic resection techniques. Further research is required to assess long-term outcomes in surveilled R1 cases, understand optimal endoscopic resection techniques and further develop local surveillance guidelines.

Novel drug treatments for pain in advanced cancer and serious illness: a focus on neuropathic pain and chemotherapy-induced peripheral neuropathy.

Drugs that are commercially available but have novel mechanisms of action should be explored as analgesics. This review will discuss haloperidol, miragabalin, palmitoylethanolamide (PEA), and clonidine as adjuvant analgesics or analgesics. Haloperidol is a sigma-1 receptor antagonist. Under stress and neuropathic injury, sigma-1 receptors act as a chaperone protein, which downmodulates opioid receptor activities and opens several ion channels. Clinically, there is only low-grade evidence that haloperidol improves pain when combined with morphine, methadone, or tramadol in patients who have cancer, pain from fibrosis, radiation necrosis, or neuropathic pain. Miragabalin is a gabapentinoid approved for the treatment of neuropathic pain in Japan since 2019. In randomized trials, patients with diabetic neuropathy have responded to miragabalin. Its long binding half-life on the calcium channel subunit may provide an advantage over other gabapentinoids. PEA belongs to a group of endogenous bioactive lipids called ALIAmides (autocoid local injury antagonist amides), which have a sense role in modulating numerous biological processes in particular non-neuronal neuroinflammatory responses to neuropathic injury and systemic inflammation. Multiple randomized trials and meta-analyses have demonstrated PEA's effectiveness in reducing pain severity arising from diverse pain phenotypes. Clonidine is an alpha2 adrenoceptor agonist and an imidazoline2 receptor agonist, which is U.S. Federal Drug Administration approved for attention deficit hyperactivity disorder in children, Tourette's syndrome, adjunctive therapy for cancer-related pain, and hypertension. Clonidine activation at alpha2 adrenoceptors causes downstream activation of inhibitory G-proteins (Gi/Go), which inhibits cyclic Adenosine monophosphate (AMP) production and hyperpolarizes neuron membranes, thus reducing allodynia. Intravenous clonidine has been used in terminally ill patients with poorly controlled symptoms, in particular pain and agitation.

Effects of Vitamin D on Migraine: A Meta-Analysis.

The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo. Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3). Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)]. although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence). Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.

External Ankle Support and Ankle Biomechanics in Chronic Ankle Instability: Systematic Review and Meta-Analysis.

To systematically review the literature to determine whether external ankle supports influence ankle biomechanics in participants with chronic ankle instability (CAI) during sport-related tasks. A literature search of MEDLINE, SPORTDiscus, and CINAHL databases was conducted in November 2021. Included studies were randomized crossover or parallel-group controlled trials in which researchers assessed ankle biomechanics during landing, running, or change of direction in participants with CAI using external ankle supports compared with no support. Two authors independently identified studies, extracted data, and assessed risk of bias (Cochrane risk-of-bias tool version 2) and quality of evidence (Grading of Recommendations Assessment, Development and Evaluation). Random-effects meta-analysis was used to compare between-groups mean differences with 95% CIs. Grading of Recommendations Assessment, Development and Evaluation recommendations were used to determine the certainty of findings. A total of 13 studies of low to moderate risk of bias were included. During landing, very low-grade evidence indicated external ankle supports reduce frontal-plane excursion (mean difference [95% CI] = -1.83° [-2.97°, -0.69°], P = .002), plantar-flexion angle at initial contact (-3.86° [-6.18°, -1.54°], P = .001), and sagittal-plane excursion (-3.45° [-5.00°, -1.90°], P < .001) but not inversion angle at initial contact (-1.00° [-3.59°, 1.59°], P = .45). During running, very low- to low-grade evidence indicated external ankle supports reduce sagittal-plane excursion (-5.21° [-8.59°, -1.83°], P = .003) but not inversion angle at initial contact (0.32° [-2.11°, 1.47°], P = .73), frontal-plane excursion (-1.31° [-3.24°, 0.63°], P = .19), or plantar-flexion angle at initial contact (-0.12° [-3.54°, 3.29°], P = .94). Studies investigating changes of direction were insufficient. Very low-grade evidence indicated external ankle supports reduce frontal-plane excursion but not inversion angle at initial contact in participants with CAI during landing. Limiting frontal-plane excursion may reduce ankle-sprain risk. Frontal-plane ankle kinematics were not influenced by external ankle supports during running. Sagittal-plane reductions were observed with external ankle supports during landing and running with low to very low certainty, but their influence on ankle-sprain risk is undetermined.

Sustainability in anaesthesia and intensive care - an obligation to turn danger into opportunity.

Sustainability in anaesthesia and intensive care - an obligation to turn danger into opportunity.

Efficacy and Safety of Clonidine in the Treatment of Acute Mania in Bipolar Disorder: A Systematic Review.

Clonidine, an alpha-2 adrenergic agonist, has been proposed as an antimanic agent that acts by reducing noradrenergic transmission. We conducted a systematic review to examine the efficacy and safety of clonidine for acute mania/hypomania. A comprehensive literature search was performed to identify randomized controlled trials (RCT) and non-randomized studies investigating the efficacy and safety of monotherapy/adjuvant treatment with clonidine for acute mania/hypomania in patients with bipolar disorder (BD). Nine studies (n = 222) met our inclusion criteria, including five RCTs (n = 159) and four non-randomized studies (n = 63). Non-randomized studies showed clonidine to help reduce symptoms of mania. However, data from placebo controlled RCTs were inconsistent. One RCT showed adjuvant clonidine as superior to placebo, whereas another RCT reported that clonidine was not better than placebo. In individual RCTs, lithium and valproate offered better antimanic effects compared to clonidine. Studies reported hypotension, depression, and somnolence as common adverse effects. Significant differences in study design and sample size contributed to high heterogeneity. This systematic review suggests low-grade evidence for clonidine as an adjuvant treatment for acute mania with mood stabilizers and inconclusive efficacy as monotherapy, warranting further well-designed RCTs.

Simvastatin as a topical anti-inflammatory: Effect on airway epithelial cell homeostasis.

Despite the significant morbidity associated with chronic rhinosinusitis in individuals with asthma (CRSwA) there is a paucity of codified, evidence-based management strategies for CRS in this population. Using PubMed, EMBASE, and Cochrane Review Databases, a systematic review was performed covering management strategies for CRSwA. 5,903 articles were screened; 70 were included for full-text analysis. After application of exclusion criteria, 53 articles comprised the qualitative synthesis. The level of evidence was graded, and benefit-harm assessments, as well as value judgment and recommendations were provided RESULTS: : Strong evidence confirms the benefit of oral and topical medications on sinonasal-specific outcomes in individuals with CRSwA; there is low-grade evidence demonstrating that these agents improve lung function and/or asthma control. Moderate-to-strong evidence suggests that endoscopic sinus surgery (ESS) improves both sinonasal- and asthma-specific quality of life. Although there is insufficient-to-low evidence to indicate that ESS improves pulmonary function in this population, data indicate a positive impact of this intervention on asthma control. Biologic medications strongly improve both subjective and objective sinonasal- and asthma-specific outcomes. Evidence supports managing CRS in individuals with CRSwA in a stepwise fashion, starting with traditional non-biologic oral and topical medication, and escalating to second-line treatments, such as ESS and biologics. Optimal treatment of individuals who suffer from CRSwA often requires concurrent, directed management of asthma, as not all CRS interventions impact asthma status. This article is protected by copyright. All rights reserved.

Revised Swedish guidelines on intravenous iodine contrast medium-induced acute kidney injury 2022: A summary.

The Swedish Society of Uroradiology has revised their computed tomography (CT) guidelines regarding iodine contrast media-induced acute kidney injury (CI-AKI). They are more cautious compared to the European Society of Urogenital Radiology and the American College of Radiology since the actual risk of CI-AKI remains uncertain in patients with moderate to severe kidney damage due to a lack of prospective controlled studies and mainly based on retrospective propensity score-matched studies with low-grade evidence. Another source of uncertainty is the imprecision of glomerular filtration rate (GFR) estimating equations. However, randomized hydration studies indictae an upper limit risk of CI-AKI of about 5% for outpatients with a GFR in the range of 30-44 or 45-59 mL/min/1.73m2 combined with multiple risk factors. Apart from GFR limits, the guideline also includes limits for systemic contrast medium exposure expressed in gram-iodine/GFR ratio.

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Centric versus eccentric engine-driven endodontic instrument design for microbial load reduction-A systematic review and meta-analysis of randomised clinical trials.

This systematic review assessed the clinical influence of centric and eccentric engine-driven instrument design for reduction in microbial load in infected root canal system. The literature search was conducted in electronic databases (PubMed, Cochrane Library, Scopus, Lilacs and Google Scholar) and grey literature till June 2022. The search strategy followed the PRISMA 2020 guidelines. Qualitative and quantitative synthesis was conducted based on the guidelines of the Cochrane Handbook. The risk of bias was assessed using the revised Cochrane criteria and quality of evidence was conducted using the Grading of Recommendation Assessment, Development and Evaluation tool. Out of 28 papers, only five papers met the inclusion criteria of this review. Studies showed reduction in microbial load after instrumentation using centric or eccentric instruments with no statistically significant difference in the meta-analysis. In conclusion, there is low-grade evidence suggesting that microbial reduction is similar using centric and eccentric instruments.

Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression.

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. In the absence of targeted therapies, it invariably progresses to advanced chronic kidney disease. To date, the only approved treatment is tolvaptan, a vasopressin V2 receptor antagonist that has been demonstrated to reduce cyst growth and attenuate the decline in kidney function. However, it has various side effects, the most frequent of which is aquaresis, leading to a significant discontinuation rate. The strategies proposed to combat aquaresis include the use of thiazides or metformin and a reduction in the dietary osmotic load. Beyond the prescription of tolvaptan, which is limited to those with a rapid and progressive decline in kidney function, dietary interventions have been suggested to protect against disease progression. Moderate sodium restriction, moderate protein intake (up to 0.8 g/kg/day), avoidance of being overweight, and increased water consumption are recommended in ADPKD guidelines, though all with low-grade evidence. The aim of the present review is to critically summarize the evidence on the effect of dietary modification on ADPKD and to offer some strategies to mitigate the adverse aquaretic effects of tolvaptan.

Multidisciplinary Approach to Treating Chronic Pain in Patients with Ehlers-Danlos Syndrome: Critically Appraised Topic.

The Ehlers–Danlos syndromes (EDS) are a group of 13 related connective tissue disorders with a combined prevalence of 1 in 5000 people, with the most common noted as hypermobile EDS (hEDS). The EDS genetic condition is thought to affect both males and females equally, although most symptomatic patients are female. EDS causes a myriad of symptoms, including skin hyperextensibility and fragility, easy bruising and bleeding, joint hypermobility, subluxation, dislocation, and chronic pain. Pain is one of the most common symptoms of EDS, leading to disability and decreased quality of life. Current guidelines for treating chronic pain in EDS are lacking. Clinicians focus on a conservative multidisciplinary approach in patients with EDS, which avoids surgical interventions and its accompanying risks of morbidity and mortality. The multidisciplinary approach includes physiotherapy, occupational therapy, cognitive behavioral therapy, and pharmacologic interventions to decrease pain. This review identifies literature examining the components of this conservative multidisciplinary approach and their effectiveness across the PubMed, EMBASE, CINAHL, Web of Science, and Trip databases, using the terms “Ehlers-Danlos Syndrome AND Pain Management” that was then subsequently evaluated. The evaluation of this current literature provides weak evidence to support the efficacy of the individual components of the conservative multidisciplinary approach. Lack of alternative approaches leaves medical providers with little choice but to suggest these pain control methods, despite low-grade evidence of weak evidence of their efficacy. More research into the pathophysiology of chronic pain in EDS could help identify additional modes and rationales for therapy.

Efficacy and safety of high versus standard dose ibuprofen for patent ductus arteriosus treatment in preterm infants: A systematic review and meta-analysis.

Several small randomized controlled trials (RCTs) and observational studies have compared high (15-20/7.5-10/7.5-10 mg/kg/dose) versus standard dose (10/5/5 mg/kg/dose) ibuprofen for patent ductus arteriosus (PDA) closure, with limited evidence on efficacy and safety. To systematically review and meta-analyze studies of high versus standard dose ibuprofen for the closure of PDA in preterm infants. Databases were searched for RCTs and observational studies assessing high compared to standard dose of ibuprofen for PDA closure for preterm infants until August 2021. The primary outcome was failure of PDA closure after the first course of ibuprofen. The secondary outcomes were the failure of PDA closure after a second course of ibuprofen, rates of PDA ligation, all-cause mortality prior to hospital discharge, bronchopulmonary dysplasia, necrotizing enterocolitis, bleeding disorders, oliguria, and serum creatinine after treatment. There were 6 studies with 369 patients (3 RCT, N = 190; 3 observational studies, N = 179). Compared to standard dose, high dose ibuprofen did not significantly decrease the failure rate of PDA closure in preterm infants after the first course (Relative risk (RR) 0.74, 95% confidence interval (CI) 0.53 -1.03, 6 studies, N = 369). High dose ibuprofen significantly decreased the rates of PDA ligation compared to standard dose (RR 0.33, 95% CI 0.16 -0.70, 5 studies, N = 309). Based on low-grade evidence, high dose ibuprofen may more effectively reduce rates of PDA ligation compared to standard dose with no increase in adverse effects, neonatal morbidities and mortality.

Surgery versus conservative treatment for traumatic acute subdural haematoma: a prospective, multicentre, observational, comparative effectiveness study

Despite being well established, acute surgery in traumatic acute subdural haematoma is based on low-grade evidence. We aimed to compare the effectiveness of a strategy preferring acute surgical evacuation with one preferring initial conservative treatment in acute subdural haematoma. We did a prospective, observational, comparative effectiveness study using data from participants enrolled in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We included patients with no pre-existing severe neurological disorders who presented with acute subdural haematoma within 24 h of traumatic brain injury. Using an instrumental variable analysis, we compared outcomes between centres according to treatment preference for acute subdural haematoma (acute surgical evacuation or initial conservative treatment), measured by the case-mix-adjusted percentage of acute surgery per centre. The primary endpoint was functional outcome at 6 months as rated with the Glasgow Outcome Scale Extended, which was estimated with ordinal regression as a common odds ratio (OR) and adjusted for prespecified confounders. Variation in centre preference was quantified with the median OR (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Between Dec 19, 2014 and Dec 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI, of whom 1407 (31%) presented with acute subdural haematoma and were included in our study. Acute surgical evacuation was done in 336 (24%) patients, by craniotomy in 245 (73%) of those patients and by decompressive craniectomy in 91 (27%). Delayed decompressive craniectomy or craniotomy after initial conservative treatment (n=982) occurred in 107 (11%) patients. The percentage of patients who underwent acute surgery ranged from 5·6% to 51·5% (IQR 12·3-35·9) between centres, with a two-times higher probability of receiving acute surgery for an identical patient in one centre versus another centre at random (adjusted MOR for acute surgery 1·8; p<0·0001]). Centre preference for acute surgery over initial conservative treatment was not associated with improvements in functional outcome (common OR per 23·6% [IQR increase] more acute surgery in a centre 0·92, 95% CI 0·77-1·09). Our findings show that treatment for patients with acute subdural haematoma with similar characteristics differed depending on the treating centre, because of variation in the preferred approach. A treatment strategy preferring an aggressive approach of acute surgical evacuation over initial conservative treatment was not associated with better functional outcome. Therefore, in a patient with acute subdural haematoma for whom a neurosurgeon sees no clear superiority for acute surgery over conservative treatment, initial conservative treatment might be considered. The Hersenstichting Nederland (also known as the Dutch Brain Foundation), the European Commission Seventh Framework Programme, the Hannelore Kohl Stiftung (Germany), OneMind (USA), Integra LifeSciences Corporation (USA), and NeuroTrauma Sciences (USA).

Impact of pharmacological interventions on biochemical hyperandrogenemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials.

Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD:-0.33; 95% CI -0.49 to -0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86nmol/L; 95% CI -1.34 to -0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD: -0.47; 95% CI -0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD: -0.37µg/dL; 95% CI -0.05 to -0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD: -1.67; 95% CI -2.27 to -1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35µg Ethinyl Estradiol (EE)/2mg cyproterone acetate (CPA)) vs placebo (MD: 103.30nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to their side effects. CRD42020178783.

Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: a systematic review and meta-analysis

Breast cancer survival rates have markedly improved. Consequently, survivorship issues have received increased attention. One common sequel of treatment is chemotherapy-induced cognitive impairment (CICI). CICI causes a range of impairments that can have a significant negative impact on quality of life. Knowledge of the prevalence of this condition is required to inform survivorship plans, and ensure adequate resource allocation and support is available for sufferers, hence a systematic review of prevalence data was performed. Medline, Scopus, CINAHL and PSYCHInfo were searched for eligible studies which included prevalence data on CICI, as ascertained though the use of self-report, or neuropsychological tests. Methodological quality of included studies was assessed. Findings were synthesised narratively, with meta-analyses being used to calculate pooled prevalence when impairment was assessed by neuropsychological tests. The review included 52 studies. Time-points considered ranged from the chemotherapy treatment period to greater than 10 years after treatment cessation. Summary prevalence figures (across time-points) using self-report, short cognitive screening tools and neuropsychological test batteries were 44%, 16% and 21–34% respectively (very low GRADE evidence). Synthesised findings demonstrate that 1 in 3 breast cancer survivors may have clinically significant cognitive impairment. Prevalence is higher when self-report based on patient experience is considered. This review highlights a number of study design issues that may have contributed to the low certainty rating of the evidence. Future studies should take a more consistent approach to the criteria used to assess impairment. Larger studies are urgently needed.