Common hand and wrist conditions: creation of UK research priorities defined by a James Lind Alliance Priority Setting Partnership

ObjectivePrioritisation of important treatment uncertainties for ‘Common Conditions Affecting the Hand and Wrist’ via a UK-based James Lind Alliance Priority Setting Partnership.SettingThis process was funded by a national charitable organisation and based in the UK.ParticipantsAnyone with experience of common conditions affecting the adult hand and wrist, including patients, carers and healthcare professionals. All treatment modalities delivered by a hand specialist, including therapists, surgeons or other allied professionals, were considered.InterventionsEstablished James Lind Alliance Priority Setting Partnership methods were employed.Electronic and paper questionnaires identified potential uncertainties. These were subsequently confirmed using relevant, up-to-date systematic reviews. A final list of top 10 research uncertainties was developed via a face-to-face workshop with representation from patients and clinicians. Impact of research was sought by surveying hand clinicians electronically.Outcome measuresThe survey responses and prioritisation—both survey and workshop based.ResultsThere were 889 individually submitted questions from the initial survey, refined to 59 uncertainties across 32 themes. Eight additional uncertainties were added from published literature before prioritisation by 261 participants and the workshop allowed the final top 10 list to be finalised. The top 10 has so far contributed to the award of over £3.8 million of competitively awarded funding.ConclusionsThe Common Conditions in the Hand and Wrist Priority Setting Partnership identified important research questions and has allowed research funders to identify grant applications which are important to both patients and clinicians

Exposure to DDT and HCH congeners and associated potential health risks through khat (Catha edulis) consumption among adults in South Wollo, Ethiopia

Khat (Catha edulis) chewing is widespread in the region of East Africa. Even low levels of organochlorine pesticides (OCPs) in khat could induce public health concern. In a market-based study, from five popular khat varieties, a total of 35 composite khat samples were analyzed for dichlorodiphenyltrichloroethane (DDT) and its main transformation products, and four hexachlorocyclohexane (HCH) isomers. Extraction was carried out by quick, easy, cheap, effective, rugged and safe method (QuEChERS). OCP concentrations were determined by head space solid phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME–GC–MS). Every sample contained β-HCH above the maximum residue limit set by the European Commission. For total DDT, this was the case for 25.7% of the samples. The ratios of (p,p′-DDD + p,p′-DDE) to p,p′-DDT were less than one for 85% of khat samples, demonstrating recent use of DDT in khat farmlands. Conversely, the ratio of β-HCH to total HCH varied from 0.56 to 0.96, implying historical input of technical HCH. Assuming a daily chewable portion of 100 g, dietary intakes of p,p′-DDT, total DDT and total HCH by adults ranged from 3.12 to 57.9, 6.49 to 80.2 and 39.2 to 51.9 ng (kg body weight)−1 day−1, respectively. These levels are below acceptable levels suggested by international organizations. Chewing khat showed lower non-cancer health risk, but showed relatively higher cancer risk in terms of OCPs. Because khat is chewed without being subjected to any treatment, uncertainties associated with estimated intakes and health risks should be low. Therefore, this practice is of great concern.

Guidelines of the Italian Society of Videosurgery in Infancy (SIVI) for the minimally invasive treatment of fetal and neonatal ovarian cysts

In the last three decades, fetal ovarian cysts were diagnosed more frequently, due to technological improvement and the increasing use of prenatal screening ultrasound. Nonetheless, treatment uncertainties are still present, either prenatally or postnatally. Recently, significant innovations on diagnosis and treatment have been proposed and a more conservative, minimally invasive approach may be offered to the Pediatrician or the Surgeon who face with this condition during prenatal or neonatal age. (...)

SARS-CoV-2 and COVID-19: From the Bench to the Bedside

First isolated in China in early 2020, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of Coronavirus Disease 2019 (COVID-19). The disease has been spreading rapidly across the globe, with the largest burden falling on China, Europe, and the United States. COVID-19 is a new clinical syndrome, characterized by respiratory symptoms with varying degrees of severity, from mild upper respiratory illness to severe interstitial pneumonia and acute respiratory distress syndrome, aggravated by thrombosis in the pulmonary microcirculation. Three main phases of disease progression have been proposed for COVID-19: an early infection phase, a pulmonary phase, and a hyperinflammation phase. Although current understanding of COVID-19 treatment is mainly derived from small uncontrolled trials that are affected by a number of biases, strong background noise, and a litany of confounding factors, emerging awareness suggests that drugs currently used to treat COVID-19 (antiviral drugs, antimalarial drugs, immunomodulators, anticoagulants, and antibodies) should be evaluated in relation to the pathophysiology of disease progression. Drawing upon the dramatic experiences taking place in Italy and around the world, here we review the changes in the evolution of the disease and focus on current treatment uncertainties and promising new therapies.

Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review

IntroductionCystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF.MethodsWe searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps.ResultsThere were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation—most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1).ConclusionsWe have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials.PROSPERO registration numberPre-results; CRD42015030111.

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders.