Generating health technology assessment evidence for rare diseases

Objectives: Rare diseases are often heterogeneous in their progression and response to treatment, with only a small population for study. This provides challenges for evidence generation to support HTA, so novel research methods are required. Methods: Discussion with an expert panel was augmented with references and case studies to explore robust approaches for HTA evidence generation for rare disease treatments. Results: Traditional RCTs can be modified using sequential, three-stage or adaptive designs to gain more power from a small patient population or to focus trial design. However, such designs need to maintain important design aspects such as randomization and blinding and be analyzed to take account of the multiple analyses performed. N-of-1 trials use within-patient randomization to test repeat periods of treatment and control until a response is clear. Such trials could be particularly valuable for rare diseases and when prospectively planned across several patients and analyzed using Bayesian techniques, a population effect can be estimated that might be of value to HTA. When the optimal outcome is unclear in a rare disease, disease specific patient reported outcomes can elucidate impacts on patients’ functioning and wellbeing. Likewise, qualitative research can be used to elicit patients’ perspectives, with just a small number of patients. Conclusions: International consensus is needed on ways to improve evidence collection and assessment of technologies for rare diseases, which recognize the value of novel study designs and analyses in a setting where the outcomes and effects of importance are yet to be agreed.</p

A review of the effectiveness of lower limb orthoses used in cerebral palsy

To produce this review, a systematic literature search was conducted for relevant articles published in the period between the date of the previous ISPO consensus conference report on cerebral palsy (1994) and April 2008. The search terms were 'cerebral and pals* (palsy, palsies), 'hemiplegia', 'diplegia', 'orthos*' (orthoses, orthosis) orthot* (orthotic, orthotics), brace or AFO

Recommendations for Using Real-Time Continuous Glucose Monitoring (rtCGM) Data for Insulin Adjustments in Type 1 Diabetes.

The clinical benefits of real time continuous glucose monitoring (rtCGM) use have been well demonstrated in both CSII- and MDI-treated individuals in large clinical trials. However, recommendations for patient use of rtCGM in everyday life situations are lacking. This article provides guidance to clinicians and patients with type 1 diabetes (T1D) in effective use of rtCGM data, including glucose rate of change (ROC) arrows, for insulin dosing adjustments and other treatment decisions. The recommendations presented here are based on our own clinical experiences as endocrinologists, our personal experiences living with T1D using rtCGM, and findings from a recent survey of T1D patients who have successfully used rtCGM in their self-management. It is important that both clinicians and people with diabetes understand the utility and limitations of rtCGM. Maintaining a collaborative clinician-user relationship remains an important factor in safe, successful rtCGM use

Catheter-associated urinary infections and consequences of using coated versus non-coated urethral catheters-outcomes of a systematic review and meta-analysis of randomized trials

Coated urethral catheters were introduced in clinical practice to reduce the risk of catheter-acquired urinary tract infection (CAUTI). We aimed to systematically review the incidence of CAUTI and adverse effects in randomized clinical trials of patients requiring indwelling bladder catheterization by comparing coated vs. non-coated catheters. This review was performed according to the 2020 PRISMA framework. The incidence of CAUTI and catheter-related adverse events was evaluated using the Cochran-Mantel-Haenszel method with a random-effects model and reported as the risk ratio (RR), 95% CI, and p-values. Significance was set at p 14 days) (RR 0.82 95% CI 0.68-0.99, p = 0.04). There was no difference between the two groups in the incidence of the need for catheter exchange or the incidence of lower urinary tract symptoms after catheter removal. The benefit of coated catheters in reducing CAUTI risk among patients requiring long-term catheterization should be balanced against the increased direct costs to health care systems when compared to non-coated catheters

Systematic Review of The Effect of High Pressure Ventilation Compared to Low Pressure Ventilation in Chronic Obstructive Pulmonary Disease Patients

Background: Chronic Obstructive Lung disease (COPD) is a progressive lung condition made from a group of diseases. It is characterised by productive cough, dyspnoea and reduced exercise tolerance. Exacerbations often lead to hospital admission, reduced QOL (QOL), a decline in lung function (LF) and inefficient ventilation. The disease currently challenges the NHS. Hypercapnic respiratory failure is treated with Non-Invasive Ventilation (NIV), domiciliary NIV is provided by a nasal or face mask and improves gaseous exchange. Pressure pre-set mode involves setting an Inspiratory Positive Airway Pressure (IPAP), there is debate regarding support of high inspiratory pressure ventilation being the effective at reducing partial pressure of carbon dioxide (PaCO2), however despite this low inspiratory positive pressures are recorded in primary studies the results have suggested although an improvement in hypercapnia, results on clinical outcomes are not significant. Objective: This systematic review explored the effects of low-pressure ventilation compared to high pressure ventilation on Lung Function, Arterial Blood Gas, Quality Of life , exercise tolerance, adherence, and identify any risks in patients with COPD on domiciliary NIV. Methods Information Sources: Bibliographic databases were searched using keywords. CINHAL, MEDLINE, AMED via EBSCO Host and The Cochrane Library. Dates were search for English language studies between 1990 and 2017. Systematic reviews and meta-analysis reference lists were hand searched to assess for additional studies. Eligibility criteria: English language, randomised control trials. Excluded were observational studies, case studies, quasi experimental, narrative literature reviews and expert commentaries. Risk of bias was assessed using the Cochrane risk bias tool and the Critical Appraisal tool for RCT’s were used to critically appraise the methods completed by one reviewer. Results: 1613 articles were assessed following deduplication. Titles and abstracts were screened against inclusion and exclusion criteria. 3 randomised control crossover trials were included in the systematic review and meta-analysis. 48 patients were Identified in total a meta-analysis was completed on the following outcomes, PaCO2, FEV1 and HRQOL. There was no significant difference in the effect of High-IPAP compared to low-IPAP in the reduction of PaCO2 (p=0.19) with a mean difference of -0.39Kpa (95% CI [-0.96, 0.19]) and results were homogenous (I2=0%, p=0.83). There was no significant difference in High-IPAP compared to low-IPAP in FEV1 (p=0.49) (95% CI 0.38 [-0.69,1.45]). Results favoured high IPAP for improvement of HRQOL however there was no significant difference between the effect of High-IPAP compared to Low-IPAP with a mean difference of 0.11 (95%CI [-1.17,0.95] p=0.77) there was no heterogeneity in results (I2=0%, P=0.59). A meta-analysis could not be completed on adherence, exacerbation and exercise tolerance as there was little or no data provided to complete a meta-analysis. Conclusion: There was no significant difference in the effect of High-IPAP compared to lowIPAP in the reduction of PaCO2, FEV1, adherence and HRQOL. Further studies are required to assess the effects on exacerbation, adverse effects and exercise tolerance as there was little or no data available on these outcomes to perform a meta-analysis and explore further. The study has implications as it demonstrates that randomised control trials are required to investigate the effect of pressure to ensure patients are provided with effective treatment of and improve patient outcomes

Effectiveness and efficiency of methods of dialysis therapy for end-stage renal disease : a review

Peer reviewedPublisher PD

Lost in Knowledge Translation: Moving Towards a Clearer Picture? Mapping the conceptualisation of knowledge translation, transfer and exchange across public health in the North East

Over recent decades the concept of evidence-based practice in health care has become part of the language of practitioners, policymakers and researchers. However, a gap between the production of research evidence and use of this evidence in practice has been identified, leading to repeated calls for solutions which will render the process more effective and efficient. It is increasingly acknowledged that getting evidence into, or out of, policy and practice arenas is not a straightforward or a linear process and to view it as such may be both misleading and overly simplistic. The term knowledge translation (KT) is used to describe the work required to close or bridge this gap and is becoming common vocabulary. However, as a concept KT (and related terms) are not yet clearly defined, nor are there agreed meanings in many areas including public health. While there is a growing body of literature exploring these concepts, using this evidence to inform public health practice, strategy, research and education is often difficult given the diverse range of sources, the worldviews upon which they are based and the need for local ‘contextual fit’. This study was commissioned by Fuse to explore how various stakeholder groups (e.g. practitioners, commissioners, academics, researchers, local authority/government) make sense of and experience the concepts and processes of knowledge translation, transfer and exchange. The study aims were to: Undertake a rapid review of recent literature syntheses pertaining to knowledge translation, exchange and transfer in public health, Explore and articulate (map) stakeholder conceptualisations and interpretations of knowledge translation, exchange and transfer in public health

Communication interventions in adult and pediatric oncology: A scoping review and analysis of behavioral targets

BackgroundImproving communication requires that clinicians and patients change their behaviors. Interventions might be more successful if they incorporate principles from behavioral change theories. We aimed to determine which behavioral domains are targeted by communication interventions in oncology.MethodsSystematic search of literature indexed in Ovid Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov (2000-October 2018) for intervention studies targeting communication behaviors of clinicians and/or patients in oncology. Two authors extracted the following information: population, number of participants, country, number of sites, intervention target, type and context, study design. All included studies were coded based on which behavioral domains were targeted, as defined by Theoretical Domains Framework.FindingsEighty-eight studies met inclusion criteria. Interventions varied widely in which behavioral domains were engaged. Knowledge and skills were engaged most frequently (85%, 75/88 and 73%, 64/88, respectively). Fewer than 5% of studies engaged social influences (3%, 3/88) or environmental context/resources (5%, 4/88). No studies engaged reinforcement. Overall, 7/12 behavioral domains were engaged by fewer than 30% of included studies. We identified methodological concerns in many studies. These 88 studies reported 188 different outcome measures, of which 156 measures were reported by individual studies.ConclusionsMost communication interventions target few behavioral domains. Increased engagement of behavioral domains in future studies could support communication needs in feasible, specific, and sustainable ways. This study is limited by only including interventions that directly facilitated communication interactions, which excluded stand-alone educational interventions and decision-aids. Also, we applied stringent coding criteria to allow for reproducible, consistent coding, potentially leading to underrepresentation of behavioral domains