Review Of Clinical Effectiveness Research Articles

Regorafenib and glioblastoma: a literature review of preclinical studies, molecular mechanisms and clinical effectiveness.

Glioblastoma IDH wild type (GBM) is a very aggressive brain tumour, characterised by an infiltrative growth pattern and by a prominent neoangiogenesis. Its prognosis is unfortunately dismal, and the median overall survival of GBM patients is short (15 months). Clinical management is based on bulk tumour removal and standard chemoradiation with the alkylating drug temozolomide, but the tumour invariably recurs leading to patient's death. Clinical options for GBM patients remained unaltered for almost two decades until the encouraging results obtained by the phase II REGOMA trial allowed the introduction of the multikinase inhibitor regorafenib as a preferred regimen in relapsed GBM treatment by the National Comprehensive Cancer Network (NCCN) 2020 Guideline. Regorafenib, a sorafenib derivative, targets kinases associated with angiogenesis (VEGFR 1-3), as well as oncogenesis (c-KIT, RET, FGFR) and stromal kinases (FGFR, PDGFR-b). It was already approved for metastatic colorectal cancers and hepatocellular carcinomas. The aim of the present review is to focus on both the molecular and clinical knowledge collected in these first three years of regorafenib use in GBM.

P059 A review of intra-articular corticosteroid injection safety and clinical effectiveness during COVID-19

Abstract Background/Aims Intraarticular corticosteroid injections (CSI) are used as a short-term treatment for inflammatory arthritis and osteoarthritis. At the outset of the COVID-19 pandemic there was concern regarding the immunosuppressive effect of steroids and the potential risk of COVID-19 infection in patients treated with CSI. There is no universal evidence-based consensus on the optimum dosing of CSI. Nationally there was a mixed response to CSI use during the COVID-19 pandemic. Early during the pandemic, our Trust advised using only the lowest BNF indicated steroid dose to minimize any potential side effects. Large joints (knees and shoulders) were injected with 40mg of Kenalog compared to 80mg pre pandemic. No previous survey has reported the incidence of covid infection post CSI. The primary aim of this project was to address this gap. A secondary aim was to review the clinical effectiveness of a ‘larger’ versus ‘smaller’ steroid dose in CSI. Methods Retrospective data collection was carried out for 107 patients who received CSI during the pandemic. All patients who received CSI within the Trust rheumatology department were followed up with a six-week phone call. During this consultation the effectiveness of the CSI was considered by asking them to score the effectiveness of the CSI out of 10 (10 being maximum improvement). The incidence of COVID-19 infection was also recorded. This data was compared to the same data from a group of patients injected with a larger dose of CSI pre-pandemic (n = 114). Results The patient reported incidence of COVID-19 infection within 6 weeks of CSI was 1.87%. Patient reported outcomes showed a mean improvement in joint symptoms of 6.97 using 80mg of kenalog, versus 5.02 improvement using the smaller 40mg dose at six week follow up. Interestingly 56% of people injected with a larger dose reported a minimum 8/10 improvement compared to 22% of patients injected with a smaller dose. Conclusion The low incidence of COVID-19 infections following CSI indicates that there is no significant correlation with increased in risk of contracting COVID-19. This study did not collect any data on outcomes of infection but at the time of the phone calls no patients had been hospitalized or died. The incidence of COVID-19 infection was below the national average. Some of the Rheumatology patients injected may have been advised to shield which may have contributed to the lower-than-expected figure. The significantly increased benefit consistently reported by patients supports the use of a higher dose steroid (Kenalog 80mg) versus lower dose (40mg) when injecting large joints in patients with arthritis. It is important to weight up the risks and benefits of CSI but this suggests that we should use the higher dose in clinical practice. Disclosure G.J. McCall: None.

Reforming the World Health Organization’s Essential Medicines List

This Viewpoint proposes restructuring the WHO Essential Medicines List to remove consideration of cost and cost-effectiveness from the expert committee reviews of clinical effectiveness, safety, and public health value, and chartering a new framework for pooled global negotiation and procurement of costly medicines included in the list.

Internet-Delivered Cognitive Behavioural Therapy for the Management of Chronic Non-Cancer Pain


 This Health Technology Assessment (HTA) was conducted to inform decision-makers about whether internet-delivered cognitive behavioural therapy (iCBT) should be offered as a treatment option for chronic non-cancer pain as part of a multidisciplinary approach when in-person cognitive behavioural therapy (CBT) would otherwise be offered. This HTA consists of a systematic review of clinical effectiveness and safety, an interview study, and an Environmental Scan.
 In this HTA, iCBT is defined as psychotherapy based on CBT principles delivered through the internet, including self-directed app-based programs (with or without therapist support) and CBT delivered through the internet in real time by a therapist (e.g., videoconference).
 The Clinical Review found there was little to no difference between iCBT and in-person CBT for most outcomes, but the evidence was very uncertain because of risk of bias, inconsistency, indirectness, and imprecision. The uncertain clinical evidence prevents a strong conclusion about the safety and effectiveness of iCBT as a treatment option when in-person CBT would otherwise be offered for chronic non-cancer pain.
 Five women living with chronic non-cancer pain were interviewed regarding their experiences with, or perspectives on, the use of iCBT for chronic pain. All the women interviewed felt iCBT has the potential to be a supportive treatment option if offered as part of comprehensive, multidisciplinary pain care. Based on their experiences, the women interviewed reported that multidisciplinary pain care does not always happen in practice, and they described potential concerns of offering iCBT in the absence of other treatments. They also indicated that determining a patient’s readiness for iCBT is important. If iCBT is determined to be appropriate, the women emphasized that a tailored treatment approach and a strong therapeutic relationship between the patient and iCBT provider might improve the success of iCBT treatment for chronic pain.
 The Environmental Scan identified 16 iCBT programs for chronic pain that are available in Canada. Many potential facilitators (e.g., improving access, improving treatment experience, efficiency, and convenience) and barriers (preference for in-person treatment, privacy concerns, technology issues, and no access to a device or internet connection) for iCBT programs in Canada were identified.
 If decision-makers decide to implement an iCBT program for chronic pain as part of their multidisciplinary pain care approach, they may wish to consider offering programs that:
 
 are guided by therapists specifically trained in chronic pain
 foster strong therapeutic relationships, encourage shared decision-making practices, and can be tailored to the needs of the person living with chronic pain
 consider the readiness and suitability of the person living with chronic pain before offering iCBT
 consider privacy and technological concerns or challenges.
 
 

Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.

ObjectiveTo conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.MethodsDatabases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for ‘HIV’ were combined with terms for ‘PrEP’ or ‘tenofovir/emtricitabine’. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.ResultsOf 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) −0.03, 95% CI −0.01 to −0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD −0.01, 95% CI −0.01 to −0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD −0.00, 95% CI −0.00 to −0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.ConclusionsPrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.PROSPERO registration numberCRD42017065937.

Systematic review and meta-analysis of clinical effectiveness of self-management interventions in Parkinson\u2019s disease

BackgroundParkinson’s disease is a complex neurodegenerative condition with significant impact on quality of life (QoL), wellbeing and function. The objective of this review is to evaluate the clinical effectiveness of self-management interventions for people with Parkinson’s disease, taking a broad view of self-management and considering effects on QoL, wellbeing and function.MethodsSystematic searches of four databases (MEDLINE, Embase, PsycINFO, Web of Science) were conducted for studies evaluating self-management interventions for people with Parkinson’s disease published up to 16th November 2020. Original quantitative studies of adults with idiopathic Parkinson’s disease were included, whilst studies of atypical Parkinsonism were excluded. Full-text articles were independently assessed by two reviewers, with data extracted by one reviewer and reliability checked by a second reviewer, then synthesised through a narrative approach and, for sufficiently similar studies, a meta-analysis of effect size was conducted (using a random-effects meta-analysis with restricted maximum likelihood method pooled estimate). Interventions were subdivided into self-management components according to PRISMS Taxonomy. Risk of bias was examined with the Cochrane Risk of Bias 2 (RoB2) tool or ROBIN-I tool as appropriate.ResultsThirty-six studies were included, evaluating a diverse array of interventions and encompassing a range of study designs (RCT n = 19; non-randomised CT n = five; within subject pre- and post-intervention comparisons n = 12). A total of 2884 participants were assessed in studies across ten countries, with greatest output from North America (14 studies) and UK (six studies). Risk of bias was moderate to high for the majority of studies, mostly due to lack of participant blinding, which is not often practical for interventions of this nature. Only four studies reported statistically significant improvements in QoL, wellbeing or functional outcomes for the intervention compared to controls. These interventions were group-based self-management education and training programmes, either alone, combined with multi-disciplinary rehabilitation, or combined with Cognitive Behaviour Therapy; and a self-guided community-based exercise programme. Four of the RCTs evaluated sufficiently similar interventions and outcomes for meta-analysis: these were studies of self-management education and training programmes evaluating QoL (n = 478). Meta-analysis demonstrated no significant difference between the self-management and the control groups with a standardised mean difference (Hedges g) of − 0.17 (− 0.56, 0.21) p = 0.38. By the GRADE approach, the quality of this evidence was deemed “very low” and the effect of the intervention is therefore uncertain.Components more frequently observed in effective interventions, as per PRISMS taxonomy analysis, were: information about resources; training or rehearsing psychological strategies; social support; and lifestyle advice and support. The applicability of these findings is weakened by the ambiguous and at times overlapping nature of self-management components.ConclusionApproaches and outcomes to self-management interventions in Parkinson’s disease are heterogenous. There are insufficient high quality RCTs in this field to show effectiveness of self-management interventions in Parkinson’s disease. Whilst it is not possible to draw conclusions on specific intervention components that convey effectiveness, there are promising findings from some studies, which could be targeted in future evaluations.

Robot-Assisted Upper Limb Training for Patients with Multiple Sclerosis: An Evidence-Based Review of Clinical Applications and Effectiveness

Upper extremities limitation is a common functional impairment in patients with Multiple Sclerosis (PwMS). Novel technological devices are increasingly used in neurorehabilitation to support motor function improvement and the quantitative assessment of motor performance during training in patients with neurological diseases. In this review, we systematically report the evidence on clinical applications and robotic-assisted arm training (RAT) in functional recovery in PwMS. PubMed/MEDLINE, the Cochrane Library, and the Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to March 2021. The 10-item PEDro scale assessed the study quality for the RCT, and the AMSTAR-2 was used to assess the quality of the systematic review. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 10 studies (161 subjects) were included. The selected studies included one systematic review, four RCTs, one randomized crossover, and four case series. The RCTs were scored as high-quality studies, while the systematic review was determined to be of low quality. Shoulder range of motion, handgrip strength, and proximal arm impairment improved after RAT. Manual dexterity, arm function, and use in daily life also ameliorated arm function. The high clinical heterogeneity of treatment programs and the variety of robot devices affects the generalizability of the study results; therefore, we emphasize the need to standardize the intervention type in future studies that evaluate the role of robotic-assisted training in PwMS. Robot-assisted treatment seems safe and useful to increase manual dexterity and the quality of movement execution in PwMS with moderate to severe disability. Additional studies with an adequate sample size and methodological rigour are warranted to drive definite conclusions.

P-P21 Endoscopic bipolar radiofrequency ablation for treating biliary obstruction caused by unresectable cancer: systematic review of clinical and cost effectiveness

Abstract Background Early evidence suggests using radiofrequency ablation (RFA) as an adjunct to stenting may improve outcomes in patients with malignant biliary obstruction. RFA can be deployed either at the initial stent insertion or to clear tumour ingrowth in a previously placed stent. Methods To assess the clinical and cost effectiveness and potential risks of RFA for malignant biliary obstruction. MEDLINE, EMBASE, Cochrane Library, Scopus, CINAHL, HTA and DARE, 3 websites and 7 trial registers were searched from 2008 to 2021. Study inclusion criteria were: malignant biliary obstruction; intervention as endoscopic RFA, either to fit a stent (primary RFA) or to clear a blocked stent (secondary RFA); primary outcomes were survival, quality of life or procedure-related adverse events. Risk of bias was assessed using the RoB 2.0 and ROBINS-I tools. Primary analysis was meta-analysis of the hazard ratio of mortality. Results 68 studies (1742 patients) were identified but only 2 randomised trials, 1 retrospective case-control study and 3 retrospective cohort studies reported a hazard ratio of death for primary RFA compared to stent-only control. The pooled hazard ratio of mortality for primary RFA compared to stent-only was 0.34 (95% confidence interval (CI) 0.21 to 0.55). There was moderate heterogeneity (I2 = 53%) however studies were consistently in favour of primary RFA. There was insufficient evidence available to analyse effectiveness in secondary RFA. No evidence relating to quality of life. There was no evidence of increased risk of cholangitis (risk ratio 1.15, 95% CI 0.63 to 2.12) or pancreatitis (risk ratio 1.34, 95% CI 0.55 to 3.25), but there was an increase in cholecystitis (risk ratio 11.47, 95% CI 2.28 to 57.66). Inconsistencies in standard reporting and study design were noted e.g. adverse outcomes and lack of standardised comparator groups. RFA was estimated to cost £2,659 and produced 0.18 QALYs more than no RFA on average. With an ICER of £14,392/QALY, RFA was likely to be cost-effective at a threshold of £20,000/QALY. The source of the vast majority of decision uncertainty lay in the effect of RFA on stent patency. Conclusions Primary RFA is associated with increased survival and appears cost-effective. The evidence for the impact of secondary RFA on survival and of quality of life is limited. There was no increase in the risk of post-ERCP cholangitis or pancreatitis but increased risk of cholecystitis. High quality RCTs to investigate primary and secondary RFA are needed with accurate documentation of quality of life, adverse event rates and survival.

Interventions Using Heart Age for Cardiovascular Disease Risk Communication: Systematic Review of Psychological, Behavioral, and Clinical Effects.

BackgroundCardiovascular disease (CVD) risk communication is a challenge for clinical practice, where physicians find it difficult to explain the absolute risk of a CVD event to patients with varying health literacy. Converting the probability to heart age is increasingly used to promote lifestyle change, but a rapid review of biological age interventions found no clear evidence that they motivate behavior change.ObjectiveIn this review, we aim to identify the content and effects of heart age interventions.MethodsWe conducted a systematic review of studies presenting heart age interventions to adults for CVD risk communication in April 2020 (later updated in March 2021). The Johanna Briggs risk of bias assessment tool was applied to randomized studies. Behavior change techniques described in the intervention methods were coded.ResultsFrom a total of 7926 results, 16 eligible studies were identified; these included 5 randomized web-based experiments, 5 randomized clinical trials, 2 mixed methods studies with quantitative outcomes, and 4 studies with qualitative analysis. Direct comparisons between heart age and absolute risk in the 5 web-based experiments, comprising 5514 consumers, found that heart age increased positive or negative emotional responses (4/5 studies), increased risk perception (4/5 studies; but not necessarily more accurate) and recall (4/4 studies), reduced credibility (2/3 studies), and generally had no effect on lifestyle intentions (4/5 studies). One study compared heart age and absolute risk to fitness age and found reduced lifestyle intentions for fitness age. Heart age combined with additional strategies (eg, in-person or phone counseling) in applied settings for 9582 patients improved risk control (eg, reduced cholesterol levels and absolute risk) compared with usual care in most trials (4/5 studies) up to 1 year. However, clinical outcomes were no different when directly compared with absolute risk (1/1 study). Mixed methods studies identified consultation time and content as important outcomes in actual consultations using heart age tools. There were differences between people receiving an older heart age result and those receiving a younger or equal to current heart age result. The heart age interventions included a wide range of behavior change techniques, and conclusions were sometimes biased in favor of heart age with insufficient supporting evidence. The risk of bias assessment indicated issues with all randomized clinical trials.ConclusionsThe findings of this review provide little evidence that heart age motivates lifestyle behavior change more than absolute risk, but either format can improve clinical outcomes when combined with other behavior change strategies. The label for the heart age concept can affect outcomes and should be pretested with the intended audience. Future research should consider consultation time and differentiate between results of older and younger heart age.International Registered Report Identifier (IRRID)NPRR2-10.1101/2020.05.03.20089938

Retrospective Review of Clinical Effects, Tolerability and Outcomes of Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) in Patients Aged 23 and Younger

Retrospective Review of Clinical Effects, Tolerability and Outcomes of Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) in Patients Aged 23 and Younger

Tumescent liposuction for lipoedema: A systematic review of clinical effectiveness and safety

Abstract Background Tumescent liposuction is an established method for surgical therapy of lipoedema - a chronic, progressive, and painful fat distribution disorder. We aimed to assess the clinical effectiveness and safety of liposuction in patients with lipoedema (stage I-III) compared to any conservative treatment, concerning patient-relevant outcomes, such as reduction of pain, reduction in the size of extremities, improvement in quality of life (QoL), and safety events. Methods A systematic review was conducted, and five databases were searched. In-/exclusion criteria were predefined according to the PICOS scheme. The internal validity of the included studies was assessed using the IHE checklist; strength of evidence for safety outcomes by the GRADE approach. Results Six prospective uncontrolled trials (467 patients) were included for assessment of clinical effectiveness. Pain outcomes (patient-reported) statistically significantly improved at six-months follow-up and up to 12 years after liposuction (six studies). Reduced sizes of patients' extremities before-and-after liposuction were reported in three studies regarding reduced leg volume and circumference of lower extremities. Statistically significant improvements in lipoedema-related QoL outcomes were reported in four studies. Seventeen post-operative adverse events occurred overall (492 patients, one additional retrospective study), including five serious adverse events. Other reported procedure-related adverse events comprise, e.g., post-operative wound infections and bleedings. Studies were judged with moderate/high risk of bias. Strength of evidence for safety outcomes was judged to be very low. Conclusions The current evidence is insufficient to prove that tumescent liposuction as safe as und more effective than conservative therapy for lipoedema. However, based on the limited evidence of the included uncontrolled studies, liposuction may potentially reduce lipoedema-associated clinical symptoms and improve the QoL. Key messages Based on the limited evidence of identified uncontrolled studies, liposuction may potentially reduce lipoedema-associated clinical symptoms and improve the quality of life of affected females. High-quality comparative studies need to be awaited. The results may support and influence the effect estimates considerably.

CONSPIRATORS: AN OLD RESPIRATORY PATHOGEN UNLEASHED BY A NEW ONE

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: There is emerging, albeit still limited data, on the interaction between COVID-19 and tuberculosis (TB). Both infections can cause dysregulation of the immune system, suggesting a biological plausibility for one disease but also for COVID-19 infection leading to TB progression. A meta-analysis recently found an increased risk of severe COVID-19 disease in the setting of tuberculosis, although this wasn't statistically significant. The second suggested biological plausibility for tuberculosis worsening or predisposing to COVID-19 infection but concluded that not enough evidence exists to understand the relationship between tuberculosis and COVID-19. Since the relationship remains uncertain, special attention should be paid to how infections from COVID-19 and tuberculosis interact, especially in endemic areas. CASE PRESENTATION: We present a 21 year-old female who presented to the emergency department (ED) with a chief complaint of shortness of breath. She had no medical history besides recent diagnosis of COVID-19 four months prior to admission, which did not require hospitalization. Since then, she reported persistent cough, and suddenly presented with shortness of breath one day prior to admission and eventually prompted ED presentation. She had no other significant symptoms nor sick contacts. In the ED, she presented with a fever of 39.3 C, tachycardia, hypoxia and tachypnea. Computed Tomography of the chest revealed bilateral pulmonary consolidation and no evidence of pulmonary embolism. An extensive autoimmune and infectious workup was unrevealing. Despite broad-spectrum antibiotics, she progressed rapidly to multi-organ failure requiring mechanical ventilation, vasopressor support, and continuous renal replacement therapy, culminating in death. Autopsy revealed alveolar hyalinization with necrotizing granulomatous infection of bilateral lungs, pleura, and pericardium, positive for acid fast bacilli. Cause of death was acute respiratory distress syndrome (ARDS) secondary to pulmonary tuberculosis. DISCUSSION: In this report, we highlight a case of a young, immunocompetent patient with no underlying risk factors who died from multi-organ failure and ARDS secondary to pulmonary and possibly disseminated tuberculosis. We suspect that her recent COVID-19 infection may have allowed latent tuberculosis to reactivate and rapidly progress to severe disease, which ultimately led to multi-organ failure and death. CONCLUSIONS: This case highlights the need for further studies to be completed on the deleterious effects of even mild COVID-19 infections, and its ability to exacerbate other types of pulmonary infections. The significance between COVID-19 and tuberculosis should be evaluated further. REFERENCE #1: Gao Y, Liu M, Chen Y, Shi S, Geng J, Tian J. Association between tuberculosis and COVID-19 severity and mortality: A rapid systematic review and meta-analysis. J Med Virol. 2021;93(1):194-196. doi:10.1002/jmv.26311 REFERENCE #2: Visca D, Ong CWM, Tiberi S, et al. Tuberculosis and COVID-19 interaction: A review of biological, clinical and public health effects. Pulmonology. 2021;27(2):151-165. doi:10.1016/j.pulmoe.2020.12.012 DISCLOSURES: No relevant relationships by Stephanie Guo, source=Web Response No relevant relationships by Florence Kan, source=Web Response No relevant relationships by Stephanie Pyskir, source=Web Response No relevant relationships by Brent Tatsuno, source=Web Response

Review of Clinical Effects and Presumed Mechanism of Action of the French Oak Wood Extract Robuvit.

Since ancient times, oak wood polyphenols are consumed concomitantly with beverages that are stored and aged in oak wood barrels. Among these polyphenols are roburins, which belong to the class of ellagitannins and only occur in oak. To date, water-extracted standardized French Quercus robur wood extract, commercially known as Robuvit®, has been investigated in 1172 subjects in over 20 published clinical trials. The results of the clinical studies are consistent with reported effects of urolithins regarding increased mitophagy, pointing to enhanced energy capacity. The Robuvit metabolite urolithin A, B, and C levels and the number of urolithin producers were found to be increased after intake of the extract. Mitophagy is a process, which assigns energy inefficient mitochondria to disassembly, followed by reconstruction to new and more efficient replacements. This effect of Robuvit was observed in different study groups. Supplementation of Robuvit is ascribed to aid chronically fatigued or burnt-out individuals to regain higher energy and activity levels. Robuvit has been further shown to improve conditions such as renal insufficiency, liver insufficiency, mild heart failure, posttraumatic stress disorder and fatigue after surgery and facilitate recovery from mild health impairments such as flu or hangover. There are also indications that Robuvit helps improve erectile function and general loss of vigor in elderly men. Ex vivo gene expression experiments using metabolites collected from Robuvit consumers point to increased ribosomal biogenesis in endothelial, neuronal, and keratinocyte cells. Higher ribosome density accelerates the peptide production to meet protein demand, making Robuvit a potential enhancer of physical endurance and performance. A study with recreational athletes, supplemented with Robuvit daily, reported significantly increased performance in triathlon.

Robot-assisted coronary artery bypass surgery: a systematic review and meta-analysis of comparative studies

Robot-assisted coronary bypass (RCAB) surgery has been proposed as an alternative to conventional coronary artery bypass grafting (C-CABG) for managing coronary heart disease, but the evidence on its performance compared to other existing treatments is unclear. The aim of this study was to assess, through a systematic review of comparative studies, the safety and clinical effectiveness of RCAB compared to C-CABG and other minimally invasive approaches for the treatment of coronary heart disease. We conducted a systematic review of primary studies in the English-language literature comparing RCAB to existing treatment options (C-CABG, minimally invasive direct coronary artery bypass [MIDCAB] and port-access coronary artery bypass [PA-CAB]) following Cochrane Collaboration guidelines. Meta-analyses were performed where appropriate. We reviewed 13 studies: 11 primary studies of RCAB (v. C-CABG in 7, v. MIDCAB in 3 and v. PA-CAB in 1) and 2 multicentre database studies (RCAB v. non-RCAB). The overall quality of the evidence was low. Most studies showed no significant benefit of RCAB over other treatments in a majority of outcome variables. Meta-analyses showed that RCAB had lower rates of pneumonia or wound infection than C-CABG, and shorter intensive care unit length of stay than C-CABG or MIDCAB. Individual studies showed that RCAB had some better outcomes than C-CABG (ventilation time, transfusion, postoperative pain, hospital length of stay) or MIDCAB (transfusion, postoperative pain, time to return to normal activities, physical functioning and hospital length of stay). The review of the database studies showed that RCAB was statistically superior to non-RCAB approaches in postoperative pain, renal failure, transfusion, reoperation for bleeding, stroke and hospital length of stay; however, the difference between the 2 groups in several of these outcomes was small. Although the findings from this review of comparative studies of RCAB appear promising and suggest that RCAB may offer some benefits to patients, in the absence of randomized controlled trials, these results should be interpreted cautiously.

Current status and perspective of CAD/CAM-produced resin composite crowns: a review of clinical effectiveness.

The purpose of the present review was to survey the available literature on computer-aided design/computer-aided manufacturing (CAD/CAM)-produced resin composite materials to provide clinicians with a current overview of the key components necessary for daily clinical use. An electronic search was conducted in the PubMed database. Peer-reviewed articles in English language on the use of resin composites in CAD/CAM dental crowns were included. A total of 122 full-text articles were identified, 15 of which were selected during the initial review. Two additional articles were also discovered through a manual search, to obtain a final total of 17 articles included in the present review. Of these, 16 were to in vitro studies, and one was an in vivo study. Findings from the in vitro studies indicate that resin composite block materials for CAD/CAM applications demonstrate excellent physical properties and are appropriate for the clinical restoration of premolars and molars. However, the in vivo study reported a low 3-year success rate, but high survival rate for resin composite CAD/CAM crowns placed in the premolar region. The key to ensuring the successful prognosis of a resin composite CAD/CAM crown is to ensure that all steps—such as proper case selection, abutment tooth preparation, occlusal adjustment, and bonding—are accurately performed.

Cancer diagnostic tools to aid decision-making in primary care: mixed-methods systematic reviews and cost-effectiveness analysis.

Tools based on diagnostic prediction models are available to help general practitioners diagnose cancer. It is unclear whether or not tools expedite diagnosis or affect patient quality of life and/or survival. The objectives were to evaluate the evidence on the validation, clinical effectiveness, cost-effectiveness, and availability and use of cancer diagnostic tools in primary care. Two systematic reviews were conducted to examine the clinical effectiveness (review 1) and the development, validation and accuracy (review 2) of diagnostic prediction models for aiding general practitioners in cancer diagnosis. Bibliographic searches were conducted on MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Library and Web of Science) in May 2017, with updated searches conducted in November 2018. A decision-analytic model explored the tools' clinical effectiveness and cost-effectiveness in colorectal cancer. The model compared patient outcomes and costs between strategies that included the use of the tools and those that did not, using the NHS perspective. We surveyed 4600 general practitioners in randomly selected UK practices to determine the proportions of general practices and general practitioners with access to, and using, cancer decision support tools. Association between access to these tools and practice-level cancer diagnostic indicators was explored. Systematic review 1 - five studies, of different design and quality, reporting on three diagnostic tools, were included. We found no evidence that using the tools was associated with better outcomes. Systematic review 2 - 43 studies were included, reporting on prediction models, in various stages of development, for 14 cancer sites (including multiple cancers). Most studies relate to QCancer® (ClinRisk Ltd, Leeds, UK) and risk assessment tools. In the absence of studies reporting their clinical outcomes, QCancer and risk assessment tools were evaluated against faecal immunochemical testing. A linked data approach was used, which translates diagnostic accuracy into time to diagnosis and treatment, and stage at diagnosis. Given the current lack of evidence, the model showed that the cost-effectiveness of diagnostic tools in colorectal cancer relies on demonstrating patient survival benefits. Sensitivity of faecal immunochemical testing and specificity of QCancer and risk assessment tools in a low-risk population were the key uncertain parameters. Practitioner- and practice-level response rates were 10.3% (476/4600) and 23.3% (227/975), respectively. Cancer decision support tools were available in 83 out of 227 practices (36.6%, 95% confidence interval 30.3% to 43.1%), and were likely to be used in 38 out of 227 practices (16.7%, 95% confidence interval 12.1% to 22.2%). The mean 2-week-wait referral rate did not differ between practices that do and practices that do not have access to QCancer or risk assessment tools (mean difference of 1.8 referrals per 100,000 referrals, 95% confidence interval -6.7 to 10.3 referrals per 100,000 referrals). There is little good-quality evidence on the clinical effectiveness and cost-effectiveness of diagnostic tools. Many diagnostic prediction models are limited by a lack of external validation. There are limited data on current UK practice and clinical outcomes of diagnostic strategies, and there is no evidence on the quality-of-life outcomes of diagnostic results. The survey was limited by low response rates. The evidence base on the tools is limited. Research on how general practitioners interact with the tools may help to identify barriers to implementation and uptake, and the potential for clinical effectiveness. Continued model validation is recommended, especially for risk assessment tools. Assessment of the tools' impact on time to diagnosis and treatment, stage at diagnosis, and health outcomes is also recommended, as is further work to understand how tools are used in general practitioner consultations. This study is registered as PROSPERO CRD42017068373 and CRD42017068375. This project was funded by the National Institute for Health Research (NIHR) Health Technology programme and will be published in full in Health Technology Assessment; Vol. 24, No. 66. See the NIHR Journals Library website for further project information.

Selective internal radiation therapies for unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma: systematic review, network meta-analysis and economic evaluation.

Hepatocellular carcinoma is the most common type of primary liver cancer. Treatment choice is dependent on underlying liver dysfunction and cancer stage. Treatment options include conventional transarterial therapies for patients with intermediate-stage disease and systemic therapy [e.g. sorafenib (Nexavar®; Bayer plc, Leverkusen, Germany)] for patients with advanced-stage disease. Selective internal radiation therapies deliver radiation to liver tumours via microspheres that are injected into the hepatic artery. There are three selective internal radiation therapies: TheraSphere™ [BTG Ltd, London, UK (now Boston Scientific, Marlborough, MA, USA)], SIR-Spheres® (Sirtex Medical Ltd, Woburn, MA, USA) and QuiremSpheres® (Quirem Medical BV, Deventer, the Netherlands). To assess the clinical effectiveness and cost-effectiveness of selective internal radiation therapies for treating patients with unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma. A search was undertaken to identify clinical effectiveness literature relating to selective internal radiation therapies and relevant comparators for the treatment of hepatocellular carcinoma. Studies were critically appraised and summarised. The network of evidence was mapped to estimate the relative effectiveness of the different selective internal radiation therapies and comparator treatments. An economic analysis evaluated the cost-effectiveness. Twenty studies were included in the clinical effectiveness review. Two large randomised controlled trials rated as having a low risk of bias [SARAH: Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled Phase 3 trial. Lancet Oncol 2017;18:1624-36; and SIRveNIB: Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018;36:1913-21] found no significant difference in overall survival or progression-free survival between SIR-Spheres and sorafenib (systemic therapy) in an advanced population, despite greater tumour response in the SIR-Spheres arm of both trials. There were some concerns regarding generalisability of the SARAH and SIRveNIB trials to UK practice. All other studies of SIR-Spheres, TheraSphere or QuiremSpheres were either rated as being at a high risk of bias or caused some concerns regarding bias. A network meta-analysis was conducted in adults with unresectable hepatocellular carcinoma who had Child-Pugh class A liver cirrhosis and were ineligible for conventional transarterial therapies. The analysis included the SARAH and SIRveNIB trials as well as a trial comparing lenvatinib (Kisplyx®; Eisai Ltd, Tokyo, Japan) (systemic therapy) with sorafenib. There were no meaningful differences in overall survival between any of the treatments. The base-case economic analysis suggested that TheraSphere may be cost-saving relative to both SIR-Spheres and QuiremSpheres. However, incremental cost differences between TheraSphere and SIR-Spheres were small. In a fully incremental analysis, which included confidential Patient Access Scheme discounts, lenvatinib was the most cost-effective treatment and dominated all selective internal radiation therapies. In pairwise comparisons of sorafenib with each selective internal radiation therapy, sorafenib also dominated all selective internal radiation therapies. The existing evidence cannot provide decision-makers with clear guidance on the comparative effectiveness of treatments in early- and intermediate-stage hepatocellular carcinoma or on the efficacy of TheraSphere or QuiremSpheres. In the advanced-stage hepatocellular carcinoma population, two large randomised trials have shown that SIR-Spheres have similar clinical effectiveness to sorafenib. None of the selective internal radiation therapies was cost-effective, being more costly and less effective than lenvatinib, both at list price and with Patient Access Scheme discounts. Future studies may wish to include early- and intermediate-stage hepatocellular carcinoma patients and the low tumour burden/albumin-bilirubin 1 subgroup of advanced-stage patients. Future high-quality studies evaluating alternative selective internal radiation therapies would be beneficial. This study is registered as PROSPERO CRD42019128383. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 48. See the NIHR Journals Library website for further project information.

The importance of oral hygiene for patients on mechanical ventilation.

The importance of oral hygiene for patients on mechanical ventilation.

A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology.

Methotrexate (MTX) is a folate analog widely used against a range of diseases including malignancies and autoimmune disorders. Its high effectiveness-price ratio also won extensive application in ophthalmology. On the other hand, although MTX has an excellent pharmacological efficacy, MTX associated side effects in clinical use, which vary from patient to patient, are nonnegligible. There is no comparatively systematic review on MTX associated side effects and its risk factors. This review aimed to reveal novel clinical approaches of MTX and its adverse effects in order to provide a reference for ophthalmic scholars in clinical application of MTX.

Economic evaluation of surgical treatments for women with stress urinary incontinence: a cost-utility and value of information analysis

ObjectivesStress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI) are common conditions that can have a negative impact on the quality of life of patients and serious cost implications...