Triggers for acute flare in adults with, or at risk of, knee osteoarthritis: a web-based case-crossover study in community-dwelling adults.

OBJECTIVE: To identify proximate causes ('triggers') of flares in adults with, or at risk of, knee osteoarthritis (OA), estimate their course and consequences, and determine higher risk individuals. METHODS: In this 13-week web-based case-crossover study adults aged ≥40 years, with or without a recorded diagnosis of knee OA, and no inflammatory arthropathy who self-reported a knee flare completed a questionnaire capturing information on exposure to 21 putative activity-related, psychosocial and environmental triggers (hazard period, ≤72 h prior). Comparisons were made with identical exposure measurements at four 4-weekly scheduled time points (non-flare control period) using conditional logistic regression. Flare was defined as a sudden onset of worsening signs and symptoms, sustained for ≥24 h. Flare characteristics, course and consequence were analysed descriptively. Associations between flare frequency and baseline characteristics were estimated using Poisson regression. RESULTS: Of 744 recruited participants (mean age [SD] 62.1 [10.2] years; 61% female), 376 reported 568 flares (hazards) and provided 867 valid control period measurements. Thirteen exposures (eight activity-related, five psychosocial/environmental) were positively associated with flare onset within 24 h (strongest odds ratio estimate, knee buckling: 9.06: 95% confidence interval [CI] 5.86, 13.99; weakest, cold/damp weather: 1.45: 95%CI 1.12, 1.87). Median flare duration was 5 days (IQR 3, 8), less common if older (incident rate ratio [IRR] 0.98: 95%CI 0.97, 0.99), more common if female (IRR 1.85: 95%CI 1.43, 2.39). CONCLUSIONS: Multiple activity-related, psychosocial and environmental exposures are implicated in triggering flares. This evidence can help inform prevention and acute symptom management for patients and clinicians.

'Acute flare-ups' in patients with, or at high risk of, knee osteoarthritis: a daily diary study with case-crossover analysis.

OBJECTIVE: To determine the natural history of flare-ups in knee osteoarthritis and their relation to physical exposures. DESIGN: Adults aged ≥45 years with a recent primary care consultation for knee OA/arthralgia completed a daily pen-and-paper diary for up to three months, including questions on average knee pain intensity, pain descriptors, other symptoms, activity interference, and selected physical exposures (prolonged kneeling, squatting, climbing stairs, ladders, and moving/lifting heavy objects). Informed by a systematic review, flare-ups were defined a priori. We calculated the rate of flare-ups in the sample, described their nature and duration, and estimated their association with physical exposures in the prior 48 h. RESULTS: 67 participants completed at least one month of diaries, 37 (55%) were female, mean age 62 years (SD 10.6) with a mean body mass index of 24.6 kg/m2 (SD 5.1). 30 participants experienced a total of 54 flare-ups (incidence density 1.12 (95%CI 0.80, 1.57) flare-ups/person-days). The median duration of flare-ups was eight days (range: 2-30). During a flare-up participants were more likely to report sharp, throbbing, stabbing, burning pain, swelling, limping, stiffness, being woken by pain, taking more analgesia, and stopping usual activities. Exposure to one or more physical exposure increased the risk of a flare-up in the subsequent 48 h (odds ratio 2.19 (95%CI: 1.22, 4.05)). CONCLUSIONS: Our study with intensive longitudinal data collection suggests acute flare-ups may be experienced by a substantial number of patients. These episodes often last a week or longer, are disruptive, prompt changes in self-management, and may be triggered by high-loading physical activities.

The PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients.

BACKGROUND: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES: To develop a prognostic index for MF. METHODS: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. CONCLUSIONS: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

A photonumeric scale for the assessment of atrophic facial photodamage.

BACKGROUND: Photonumeric scales have consistently shown superiority over descriptive equivalents. They have the advantage of providing a consistent visual frame of reference by minimizing variability in perception and subjectivity. A photonumeric scale to assess hypertrophic facial photodamage already exists. However, there is currently no objective measure for atrophic facial photodamage. To address this, we have devised a nine-point photonumeric standardized scale. OBJECTIVES: To design, test and validate a photonumeric scale for the assessment of atrophic facial photodamage against a descriptive scale for the same indication. METHODS: A pool of 393 facial photographs (en face and 45° oblique) from 131 individuals with atrophic facial photodamage was created. Five photographic standards were selected and assigned grades zero through to eight, where zero is no photodamage and eight is severe atrophic photodamage, thus making a nine-point scale. Twenty photographs spanning the entire range of values were selected to test the scale. Testing was performed alongside a descriptive equivalent. A panel of 10 dermatologists, 10 nondermatology clinicians and 14 dermatology scientists marked the two scales; marking was repeated 1 week later. RESULTS: There was a significantly greater agreement between the graders using the photonumeric scale than the descriptive scale (kappa values 0·71 and 0·37 with standardized errors of 0·57 and 0·17, respectively) with no significant difference in repeatability between the two methods (P < 0·05). CONCLUSIONS: The study describes a new photonumeric scale for atrophic photodamage. This would be a useful adjunct in both the clinical and research settings.

Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven. OBJECTIVES: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA). SEARCH STRATEGY: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour. SELECTION CRITERIA: We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment. DATA COLLECTION AND ANALYSIS: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed. MAIN RESULTS: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01). CONCLUSION: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice. TWEETABLE ABSTRACT: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.

Multidimensional Treatment Foster Care for Adolescents in English care: randomised trial and observational cohort evaluation.

BACKGROUND: Children in care often have poor outcomes. There is a lack of evaluative research into intervention options. AIMS: To examine the efficacy of Multidimensional Treatment Foster Care for Adolescents (MTFC-A) compared with usual care for young people at risk in foster care in England. METHOD: A two-arm single (assessor) blinded randomised controlled trial (RCT) embedded within an observational quasi-experimental case-control study involving 219 young people aged 11-16 years (trial registration: ISRCTN 68038570). The primary outcome was the Child Global Assessment Scale (CGAS). Secondary outcomes were ratings of educational attendance, achievement and rate of offending. RESULTS: The MTFC-A group showed a non-significant improvement in CGAS outcome in both the randomised cohort (n = 34, adjusted mean difference 1.3, 95% CI -7.1 to 9.7, P = 0.75) and in the trimmed observational cohort (n = 185, adjusted mean difference 0.95, 95% CI -2.38 to 4.29, P = 0.57). No significant effects were seen in secondary outcomes. There was a possible differential effect of the intervention according to antisocial behaviour. CONCLUSIONS: There was no evidence that the use of MTFC-A resulted in better outcomes than usual care. The intervention may be more beneficial for young people with antisocial behaviour but less beneficial than usual treatment for those without.

Why do depressed individuals have difficulties in their parenting role?

Although existing research has shown that depression in parents has a negative effect on parent-child interactions, the mechanisms underpinning impaired parenting are still unknown. In this editorial, we review core difficulties that have been noted in depressed individuals including reduced positive and increased negative affect, poor emotion regulation, executive function deficits, reduced motivation and rumination, and discuss how each of these can alter parenting. We suggest that these causal processes are inter-related and can interact with one another in affecting parenting. We conclude that an improved understanding of these processes will have implications for the development of more specific and potentially more effective treatments that have the potential to break the intergenerational transmission of psychopathology.

Social needs screening in primary care: A tool in the fight for health equity?

Progress on addressing health inequalities is slow and in many places around the world the gap between the privileged and the disadvantaged is widening. This is driven largely by an unfair and unequal distribution of the social determinants of health. While upstream policy and agenda commitment is needed to improve social determinants of health at a population level, healthcare also has a role. Currently social information is sporadically collected and used in healthcare. Improving our understanding of social problems is crucial in targeting services and to reduce the overreliance on area-level measures of deprivation. This has the potential to improve patient care as well as more accurately capture socio-economic disadvantage. Here we argue that there is a role for primary care in screening for social needs to help address inequalities. Social needs screening, more commonly used in North America than Europe, aims to systematically collect social information in health and care settings. Healthcare professionals ask patients about social issues including employment, finances, housing, education and social isolation and this information is used to prompt referral to community services to address any need identified. Social needs screening has potential to address negative impacts of social determinants of health at an individual and population level. Providing a reliable measure of social need, screening gives healthcare professionals an opportunity to tailor and improve quality of care for patients and offer individualised support. It has been shown to improve individual social and health outcomes and positively impact healthcare utilisation. At a population level, social needs screening can improve the data on social determinants of health and therefore support policy makers and service delivery leaders to target resources and services more effectively to the communities most in need. Implementing social needs screening must take account of local healthcare service capacity and available community resources but where sustainable, effective programmes can be introduced, the potential benefits are manifold. While primary care alone cannot solve the root causes of health inequalities, we argue it could be a powerful actor in the fight for health equity.

U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments. OBJECTIVES: To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect. METHODS: Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature. RESULTS: The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting. CONCLUSION: Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose.

Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Insulin-requiring diabetes in rural Ethiopia: should we reopen the case for malnutrition-related diabetes?

AIMS/HYPOTHESIS: We evaluated the incidence of insulin-requiring diabetes in a rural area of sub-Saharan Africa. METHODS: Health surveillance data from a chronic disease programme in two zones of Ethiopia, Gondar and Jimma, were studied. The two zones have a population of more than 5,000,000 people. RESULTS: In Gondar Zone (1995-2008) and Jimma Zone (2002-2008) 2,280 patients presented with diabetes, of whom 1,029 (45%) required insulin for glycaemic control at diagnosis. The annual incidence of insulin-requiring diabetes was 2.1 (95% CI 2.0-2.2) per 100,000 and was twice as high in men (2.9 per 100,000) as in women (1.4 per 100,000). In both sexes incidence rates peaked at the age of 25 to 29 years. Incidence rates in the urban areas of Gondar and Jimma were five times higher than in the surrounding rural areas. Patients with insulin-requiring diabetes from rural and urban areas had a very low BMI and most were subsistence farmers or unemployed. CONCLUSIONS/INTERPRETATION: The typical patient with diabetes in rural Ethiopia is an impoverished, young adult male with severe symptoms requiring insulin for glycaemic control. The low incidence rates in rural compared with urban areas suggest that many cases of this disease remain undiagnosed. The disease phenotype encountered in this area of Africa is very different from the classical type 1 diabetes seen in the West and most closely resembles previous descriptions of malnutrition-related diabetes, a category not recognised in the current WHO Diabetes Classification. We believe that the case for this condition should be reopened.

Primary care treatment of epilepsy in rural Ethiopia: causes of default from follow-up.

BACKGROUND: In 1998, we set up nurse-led epilepsy clinics in five rural health centres around Gondar in northern Ethiopia. Despite good treatment outcomes, two years after registration only 40% of patients were still under follow-up. AIM: The purpose of this study was to examine the causes of default and factors that might improve adherence to follow-up. METHOD: The study was carried out at one of the five health centres. Patients who had defaulted from follow-up were identified from the clinic register. Trained enumerators visited the patients' villages and administered a questionnaire to the patients, or relatives if the patient was not available. RESULTS: 113 patients were traced. 28 (25%) had died and 21 (19%) had moved from the area. Of the remaining 64 patients, seven were accessing treatment from another source and 13 were in remission off treatment. 44 patients were still experiencing seizures and were on no treatment or had reverted to traditional remedies. The main reason given for default, in 44% of the patients, was difficulty in travelling to the health centre. 12% claimed that they preferred traditional remedies and 9% felt that they had not been improved by medical treatment. CONCLUSION: Despite decentralisation of care to rural health centres, the most common reason for default was the distance to travel to the health centre. Further decentralisation of care to a community level coupled with improved education may reduce default from follow-up.

Non-communicable disease clinics in rural Ethiopia: why patients are lost to follow-up.

BACKGROUND: Providing medical care for non-communicable diseases (NCDs) in rural sub-Saharan Africa has proved to be difficult because of poor treatment adherence and frequent loss to follow-up (LTFU). The reasons for this are poorly understood. OBJECTIVE: To investigate LTFU among patients with two different but common NCDs who attended rural Ethiopian health centres. METHOD: The study was based in five health centres in southern Ethiopia with established NCD clinics run by nurses and health officers. Patients with epilepsy or hypertension who were lost to follow-up and non-LTFU comparison patients were identified and traced; a questionnaire was administered enquiring about the reasons for LTFU. RESULTS: Of the 147 LTFU patients successfully located, 62 had died, moved away or were attending other medical facilities. The remaining 85 patients were compared with 211 non-LFTU patients. The major factors associated with LTFU were distance from the clinic, associated costs and a preference for traditional treatments, together with a misunderstanding of the nature of NCD management. CONCLUSIONS: The delivery of affordable care closer to the patients' homes has the greatest potential to address the problem of LTFU. Also needed are increased levels of patient education and interaction with traditional healers to explain the nature of NCDs and the need for life-long management.

The effectiveness of glibenclamide in women with gestational diabetes.

BACKGROUND: Several studies have suggested that glibenclamide may be used safely and effectively in women with gestational diabetes mellitus (GDM). The aim of our study was to assess effectiveness and safety of glibenclamide for GDM in UK clinical practice. METHODS: Women with GDM requiring pharmacological therapy were offered a choice of insulin or glibenclamide. Maternal and foetal outcomes were assessed in women treated with insulin (45) or glibenclamide (44) and also compared with women treated with diet alone (55). RESULTS: Thirty-four (77%) achieved adequate glycaemic control with glibenclamide. Women choosing glibenclamide were more likely to be Asian and had higher fasting and 2-h glucose at diagnosis than those choosing insulin. There was no difference in maternal age or parity. Ten women treated with glibenclamide switched to insulin [inadequate control (7), unpredictable hypoglycaemia (1) and other reason (2)]. There was no difference in mode of birth, birth weight or birth weight centile between groups. One stillbirth occurred with glibenclamide. Glibenclamide treatment was associated with lower Apgar scores and increased neonatal jaundice. Neonatal hypoglycaemia occurred more frequently in babies of women treated with either glibenclamide or insulin. CONCLUSION: The use of glibenclamide in pregnancy is associated with adequate glycaemic control in 77% of women and achieved similar foetal outcomes to women treated with insulin.

Anaesthesia and hospital links: strengthening healthcare through South-North hospital partnerships.

Health services can respond to the needs of the poorest people in developing countries if those who work in the front line of health care are supported and motivated and if development needs in services and training programmes can be filled. This can be achieved when a Health Link between a southern hospital and/or training school and its northern counterpart is designed to build a disciplined and long-term programme of staff development including the needs of anaesthetic services, which meets the needs identified by the southern partner. Development of anaesthetic practice is best carried out in the context of an institution-wide Health Link where not only the staff and systems involved in anaesthesia but all the essential 'back office' or support services are also supported and developed.