Royal United Hospital Bath NHS Trust

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

BACKGROUND: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. METHODS: ). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. FINDINGS: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). INTERPRETATION: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. FUNDING: Cancer Research UK.

Severe acute respiratory syndrome-corona virus-2, which causes coronavirus disease 2019 (COVID-19), is highly contagious. Airway management of patients with COVID-19 is high risk to staff and patients. We aimed to develop principles for airway management of patients with COVID-19 to encourage safe, accurate and swift performance. This consensus statement has been brought together at short notice to advise on airway management for patients with COVID-19, drawing on published literature and immediately available information from clinicians and experts. Recommendations on the prevention of contamination of healthcare workers, the choice of staff involved in airway management, the training required and the selection of equipment are discussed. The fundamental principles of airway management in these settings are described for: emergency tracheal intubation; predicted or unexpected difficult tracheal intubation; cardiac arrest; anaesthetic care; and tracheal extubation. We provide figures to support clinicians in safe airway management of patients with COVID-19. The advice in this document is designed to be adapted in line with local workplace policies.

INTRODUCTION: In 2008, the UK National Osteoporosis Guideline Group (NOGG) produced a guideline on the prevention and treatment of osteoporosis, with an update in 2013. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women and men age 50 years or over. METHODS: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment, lifestyle measures and pharmacological interventions, duration and monitoring of bisphosphonate therapy, glucocorticoid-induced osteoporosis, osteoporosis in men, postfracture care and intervention thresholds. CONCLUSION: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals who are involved in its management.

Personal protective equipment has become an important and emotive subject during the current coronavirus disease 2019 epidemic. Coronavirus disease 2019 is predominantly caused by contact or droplet transmission attributed to relatively large respiratory particles which are subject to gravitational forces and travel only approximately 1 metre from the patient. Airborne transmission may occur if patient respiratory activity or medical procedures generate respiratory aerosols. These aerosols contain particles that may travel much longer distances and remain airborne longer, but their infective potential is uncertain. Contact, droplet and airborne transmission are each relevant during airway manoeuvres in infected patients, particularly during tracheal intubation. Personal protective equipment is an important component, but only one part, of a system protecting staff and other patients from coronavirus disease 2019 cross-infection. Appropriate use significantly reduces risk of viral transmission. Personal protective equipment should logically be matched to the potential mode of viral transmission occurring during patient care - contact, droplet or airborne. Recommendations from international organisations are broadly consistent, but equipment use is not. Only airborne precautions include a fitted high-filtration mask, and this should be reserved for aerosol generating procedures. Uncertainty remains around certain details of personal protective equipment including use of hoods, mask type and the potential for re-use of equipment.

Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. Our findings suggest that the number of new cases annually will rise from 1·4 million in 2020 to 2·9 million by 2040. This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it. We have projected trends in the incidence of prostate cancer and related mortality (assuming no changes in treatment) in the next 10–15 years, and make recommendations on how to deal with these issues.
\nFor the Commission, we established four working groups, each of which examined a different aspect of prostate cancer: epidemiology and future projected trends in cases, the diagnostic pathway, treatment, and management of advanced disease, the main problem for most men diagnosed with prostate cancer worldwide. Throughout we have separated problems in high-income countries (HICs) from those in low-income and middle-income countries (LMICs), although we acknowledge that this distinction can be an oversimplification (some rich patients in LMICs can access high-quality care, whereas many patients in HICs, especially the USA, cannot because of inadequate insurance coverage). The burden of disease globally is already substantial, but options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented. For men diagnosed with advanced disease, optimal use of available technologies, adjusted to the resource levels available, could produce improved outcomes. We also found that demographic changes (ie, changing age structures and increasing life expectancy) in LMICs will drive big increases in prostate cancer, and cases are also projected to rise in high-income countries. This projected rise in cases has driven the main thrust of our recommendations throughout. Dealing with this rise in cases will require urgent and radical interventions, particularly in LMICs, including an emphasis on education (both of health professionals and the general population) linked to outreach programmes to increase awareness. If implemented, these interventions would shift the case mix from advanced to earlier-stage disease, which in turn would necessitate different treatment approaches: earlier diagnosis would prompt a shift from palliative to curative therapies based around surgery and radiotherapy. Although age-adjusted mortality from prostate cancer is falling in HICs, it is rising in LMICs. And, despite large, well known differences in disease incidence and mortality by ethnicity (eg, incidence in men of African heritage is roughly double that in men of European heritage), most prostate cancer research has disproportionally focused on men of European heritage. Without urgent action, these trends will cause global deaths from prostate cancer to rise rapidly.

PURPOSE: To estimate prevalence and severity of patients' self-perceived supportive care needs in the immediate post-treatment phase and identify predictors of unmet need. PATIENTS AND METHODS: A multicenter, prospective, longitudinal survey was conducted. Sixty-six centers recruited patients for 12 weeks. Patients receiving treatment for the following cancers were recruited: breast, prostate, colorectal, and gynecologic cancer and non-Hodgkin's lymphoma. Measures of supportive care needs, anxiety and depression, fear of recurrence, and positive and negative affect were completed at the end of treatment (T0) and 6 months later (T1). RESULTS: Of 1,850 patients given questionnaire packs, 1,425 (79%) returned questionnaires at T0, and 1,152 (62%) returned questionnaires at T1. Mean age was 61 years; and most respondents were female (69%) and had breast cancer (57%). Most patients had no or few moderate or severe unmet supportive care needs. However, 30% reported more than five unmet needs at baseline, and for 60% of these patients, the situation did not improve. At both assessments, the most frequently endorsed unmet needs were psychological needs and fear of recurrence. Logistic regression revealed several statistically significant predictors of unmet need, including receipt of hormone treatment, negative affect, and experiencing an unrelated significant event between assessments. CONCLUSION: Most patients do not express unmet needs for supportive care after treatment. Thirty percent reported more than five moderate or severe unmet needs at both assessments. Unmet needs were predicted by hormone treatment, negative mood, and experiencing a significant event. Our results suggest that there is a proportion of survivors with unmet needs who might benefit from the targeted application of psychosocial resources.

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management. INTRODUCTION: The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. METHODS: Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS: Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement. CONCLUSION: The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases.

Summary The emergence of coronavirus disease 2019 (COVID‐19) has led to high demand for intensive care services worldwide. However, the mortality of patients admitted to the intensive care unit (ICU) with COVID‐19 is unclear. Here, we perform a systematic review and meta‐analysis, in line with PRISMA guidelines, to assess the reported ICU mortality for patients with confirmed COVID‐19. We searched MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with COVID‐19. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from the ICU or death. The definition thus did not include patients still alive on ICU. Twenty‐four observational studies including 10,150 patients were identified from centres across Asia, Europe and North America. In‐ICU mortality in reported studies ranged from 0 to 84.6%. Seven studies reported outcome data for all patients. In the remaining studies, the proportion of patients discharged from ICU at the point of reporting varied from 24.5 to 97.2%. In patients with completed ICU admissions with COVID‐19 infection, combined ICU mortality (95%CI) was 41.6% (34.0–49.7%), I 2 = 93.2%). Sub‐group analysis by continent showed that mortality is broadly consistent across the globe. As the pandemic has progressed, the reported mortality rates have fallen from above 50% to close to 40%. The in‐ICU mortality from COVID‐19 is higher than usually seen in ICU admissions with other viral pneumonias. Importantly, the mortality from completed episodes of ICU differs considerably from the crude mortality rates in some early reports.

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.

BACKGROUND: Successful tracheal intubation during general anaesthesia traditionally requires a line of sight to the larynx attained by positioning the head and neck and using a laryngoscope to retract the tongue and soft tissues of the floor of the mouth. Difficulties with intubation commonly arise, and alternative laryngoscopes that use digital and/or fibreoptic technology have been designed to improve visibility when airway difficulty is predicted or encountered. Among these devices, a rigid videolaryngoscope (VLS) uses a blade to retract the soft tissues and transmits a lighted video image to a screen. OBJECTIVES: Our primary objective was to assess whether use of videolaryngoscopy for tracheal intubation in adults requiring general anaesthesia reduces risks of complications and failure compared with direct laryngoscopy. Our secondary aim was to assess the benefits and risks of these devices in selected population groups, such as adults with obesity and those with a known or predicted difficult airway. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 10 February 2015. Our search terms were relevant to the review question and were not limited by outcomes. We carried out clinical trials register searches and forward and backward citation tracking. We reran the search on 12 January 2016; we added potential new studies of interest from the 2016 search to a list of 'Studies awaiting classification', and we will incorporate these studies into the formal review during the review update. SELECTION CRITERIA: We considered all randomized controlled trials and quasi-randomized studies with adult patients undergoing laryngoscopy performed with a VLS or a Macintosh laryngoscope in a clinical, emergency or out-of-hospital setting. We included parallel and cross-over study designs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data, consulting a third review author to resolve disagreements. We used standard Cochrane methodological procedures, including assessment of risk of bias. MAIN RESULTS: = 96%). AUTHORS' CONCLUSIONS: Videolaryngoscopes may reduce the number of failed intubations, particularly among patients presenting with a difficult airway. They improve the glottic view and may reduce laryngeal/airway trauma. Currently, no evidence indicates that use of a VLS reduces the number of intubation attempts or the incidence of hypoxia or respiratory complications, and no evidence indicates that use of a VLS affects time required for intubation.

Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram.

BACKGROUND: Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of the effectiveness of these tests in a real-world setting. We therefore aimed to determine whether knowledge of the circulating concentration of placental growth factor (PlGF), an angiogenic factor, integrated with a clinical management algorithm, decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia, and whether this approach reduced subsequent maternal or perinatal adverse outcomes. METHODS: We did a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial in 11 maternity units in the UK, which were each responsible for 3000-9000 deliveries per year. Women aged 18 years and older who presented with suspected pre-eclampsia between 20 weeks and 0 days of gestation and 36 weeks and 6 days of gestation, with a live, singleton fetus were invited to participate by the clinical research team. Suspected pre-eclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Women were approached individually, they consented for study inclusion, and they were asked to give blood samples. We randomly allocated the maternity units, representing the clusters, to blocks. Blocks represented an intervention initiation time, which occurred at equally spaced 6-week intervals throughout the trial. At the start of the trial, all units had usual care (in which PlGF measurements were also taken but were concealed from clinicians and women). At the initiation time of each successive block, a site began to use the intervention (in which the circulating PlGF measurement was revealed and a clinical management algorithm was used). Enrolment of women continued for the duration of the blocks either to concealed PlGF testing, or after implementation, to revealed PlGF testing. The primary outcome was the time from presentation with suspected pre-eclampsia to documented pre-eclampsia in women enrolled in the trial who received a diagnosis of pre-eclampsia by their treating clinicians. This trial is registered with ISRCTN, number 16842031. FINDINGS: Between June 13, 2016, and Oct 27, 2017, we enrolled and assessed 1035 women with suspected pre-eclampsia. 12 (1%) women were found to be ineligible. Of the 1023 eligible women, 576 (56%) women were assigned to the intervention (revealed testing) group, and 447 (44%) women were assigned to receive usual care with additional concealed testing (concealed testing group). Three (1%) women in the revealed testing group were lost to follow-up, so 573 (99%) women in this group were included in the analyses. One (<1%) woman in the concealed testing group withdrew consent to follow-up data collection, so 446 (>99%) women in this group were included in the analyses. The median time to pre-eclampsia diagnosis was 4·1 days with concealed testing versus 1·9 days with revealed testing (time ratio 0·36, 95% CI 0·15-0·87; p=0·027). Maternal severe adverse outcomes were reported in 24 (5%) of 447 women in the concealed testing group versus 22 (4%) of 573 women in the revealed testing group (adjusted odds ratio 0·32, 95% CI 0·11-0·96; p=0·043), but there was no evidence of a difference in perinatal adverse outcomes (15% vs 14%, 1·45, 0·73-2·90) or gestation at delivery (36·6 weeks vs 36·8 weeks; mean difference -0·52, 95% CI -0·63 to 0·73). INTERPRETATION: We found that the availability of PlGF test results substantially reduced the time to clinical confirmation of pre-eclampsia. Where PlGF was implemented, we found a lower incidence of maternal adverse outcomes, consistent with adoption of targeted, enhanced surveillance, as recommended in the clinical management algorithm for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study. FUNDING: National Institute for Health Research.

This guideline updates and replaces the 5th edition of the Standards of Monitoring published in 2015. The aim of this document is to provide guidance on the minimum standards for monitoring of any patient undergoing anaesthesia or sedation under the care of an anaesthetist. The recommendations are primarily aimed at anaesthetists practising in the UK and Ireland, but it is recognised that these guidelines may also be of use in other areas of the world. Minimum standards for monitoring patients during anaesthesia and in the recovery phase are included. There is also guidance on monitoring patients undergoing sedation and during transfer. There are new sections specifically discussing capnography, sedation and regional anaesthesia. In addition, the indications for processed electroencephalogram and neuromuscular monitoring have been updated.

PURPOSE: Infantile spasms is a severe infantile seizure disorder. Several factors affect developmental outcome, especially the underlying etiology of the spasms. Treatment also affects outcome. Both age at onset of spasms and lead time to treatment (the time from onset of spasms to start of treatment) may be important. We investigated these factors. METHODS: Developmental assessment using Vineland Adaptive Behaviour Scales (VABS) at 4 years of age in infants enrolled in the United Kingdom Infantile Spasms Study. Date of or age at onset of spasms was obtained prospectively. Lead time to treatment was then categorized into five categories. The effects of lead time to treatment, age of onset of spasms, etiology, and treatment on developmental outcome were investigated using multiple linear regression. KEY FINDINGS: Age of onset ranged (77 infants) from <1 to 10 months (mean 5.2, standard deviation 2.1). Lead time to treatment was 7 days or less in 11, 8-14 days in 16, 15 days to 1 month in 8, 1-2 months in 15, >2 months in 21 and not known in 6. Each month of reduction in age at onset of spasms was associated with a 3.1 [95% confidence interval (CI) 0.64-5.5, p = 0.03] decrease, and each increase in category of lead time duration associated with a 3.9 (95% CI 7.3-0.4, p = 0.014) decrease in VABS, respectively. There was a significant interaction between treatment allocation and etiology with the benefit in VABS in those allocated steroid therapy being in children with no identified etiology (coefficient 29.9, p=0.004). SIGNIFICANCE: Both prompt diagnosis and prompt treatment of infantile spasms may help prevent subsequent developmental delay. Younger infants may be more at risk from the epileptic encephalopathy than older infants.

There is widespread evidence both of the exclusion of older people from clinical research, and of under-recruitment to clinical trials. This review and opinion piece provides practical advice to assist researchers both to adopt realistic, achievable recruitment rates and to increase the number of older people taking part in research. It analyses 14 consecutive recently published trials, providing the number needed to be screened to recruit one older participant (around 3:1), numbers excluded (up to 49%), drop out rates (5-37%) and whether the planned power was achieved. The value of planning and logistics are outlined, and approaches to optimising recruitment in hospital, primary care and care home settings are discussed, together with the challenges of involving older adults with mental incapacity and those from minority groups in research. The increasingly important task of engaging older members of the public and older patients in research is also discussed. Increasing the participation of older people in research will improve the generalisability of research findings and inform best practice in the clinical management of the growing older population.

BACKGROUND: Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS: Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS: The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS: Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40 .).

BACKGROUND: Chronic pain (i.e. pain lasting longer than three months) is common. Psychological therapies (e.g. cognitive behavioural therapy) can help people to cope with pain, depression and disability that can occur with such pain. Treatments currently are delivered via hospital out-patient consultation (face-to-face) or more recently through the Internet. This review looks at the evidence for psychological therapies delivered via the Internet for adults with chronic pain. OBJECTIVES: Our objective was to evaluate whether Internet-delivered psychological therapies improve pain symptoms, reduce disability, and improve depression and anxiety for adults with chronic pain. Secondary outcomes included satisfaction with treatment/treatment acceptability and quality of life. SEARCH METHODS: We searched CENTRAL (Cochrane Library), MEDLINE, EMBASE and PsycINFO from inception to November 2013 for randomised controlled trials (RCTs) investigating psychological therapies delivered via the Internet to adults with a chronic pain condition. Potential RCTs were also identified from reference lists of included studies and relevant review articles. In addition, RCTs were also searched for in trial registries. SELECTION CRITERIA: Peer-reviewed RCTs were identified and read in full for inclusion. We included studies if they used the Internet to deliver the primary therapy, contained sufficient psychotherapeutic content, and promoted self-management of chronic pain. Studies were excluded if the number of participants in any arm of the trial was less than 20 at the point of extraction. DATA COLLECTION AND ANALYSIS: Fifteen studies met the inclusion criteria and data were extracted. Risk of bias assessments were conducted for all included studies. We categorised studies by condition (headache or non-headache conditions). Four primary outcomes; pain symptoms, disability, depression, and anxiety, and two secondary outcomes; satisfaction/acceptability and quality of life were extracted for each study immediately post-treatment and at follow-up (defined as 3 to 12 months post-treatment). MAIN RESULTS: Fifteen studies (N= 2012) were included in analyses. We assessed the risk of bias for included studies as low overall. We identified nine high 'risk of bias' assessments, 22 unclear, and 59 low 'risk of bias' assessments. Most judgements of a high risk of bias were due to inadequate reporting.Analyses revealed seven effects. Participants with headache conditions receiving psychological therapies delivered via the Internet had reduced pain (number needed to treat to benefit = 2.72, risk ratio 7.28, 95% confidence interval (CI) 2.67 to 19.84, p < 0.01) and a moderate effect was found for disability post-treatment (standardised mean difference (SMD) ‒0.65, 95% CI ‒0.91 to ‒0.39, p < 0.01). However, only two studies could be entered into each analysis; hence, findings should be interpreted with caution. There was no clear evidence that psychological therapies improved depression or anxiety post-treatment (SMD -0.26, 95% CI -0.87 to 0.36, p > 0.05; SMD -0.48, 95% CI -1.22 to 0.27, p > 0.05), respectively. In participants with non-headache conditions, psychological therapies improved pain post-treatment (p < 0.01) with a small effect size (SMD -0.37, 95% CI -0.59 to -0.15), disability post-treatment (p < 0.01) with a moderate effect size (SMD -0.50, 95% CI -0.79 to -0.20), and disability at follow-up (p < 0.05) with a small effect size (SMD -0.15, 95% CI -0.28 to -0.01). However, the follow-up analysis included only two studies and should be interpreted with caution. A small effect was found for depression and anxiety post-treatment (SMD -0.19, 95% CI -0.35 to -0.04, p < 0.05; SMD -0.28, 95% CI -0.49 to -0.06, p < 0.01), respectively. No clear evidence of benefit was found for other follow-up analyses. Analyses of adverse effects were not possible.No data were presented on satisfaction/acceptability. Only one study could be included in an analysis of the effect of psychological therapies on quality of life in participants with headache conditions; hence, no analysis could be undertaken. Three studies presented quality of life data for participants with non-headache conditions; however, no clear evidence of benefit was found (SMD -0.27, 95% CI -0.54 to 0.01, p > 0.05). AUTHORS' CONCLUSIONS: There is insufficient evidence to make conclusions regarding the efficacy of psychological therapies delivered via the Internet in participants with headache conditions. Psychological therapies reduced pain and disability post-treatment; however, no clear evidence of benefit was found for depression and anxiety. For participants with non-headache conditions, psychological therapies delivered via the Internet reduced pain, disability, depression, and anxiety post-treatment. The positive effects on disability were maintained at follow-up. These effects are promising, but considerable uncertainty remains around the estimates of effect. These results come from a small number of trials, with mostly wait-list controls, no reports of adverse events, and non-clinical recruitment methods. Due to the novel method of delivery, the satisfaction and acceptability of these therapies should be explored in this population. These results are similar to those of reviews of traditional face-to-face therapies for chronic pain.

INTRODUCTION: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively. RESULTS: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.