Caryophylliids (Anthozoa, Scleractinia) and mitochondrial gene order: Insights from mitochondrial and nuclear phylogenomics.

Molecularly, the family Caryophylliidae is polyphyletic and different sets of genetic data converge towards a consensus that a taxonomic review of this family is necessary. Overall, the order of genes in the mitochondrial genome (mitogenome) together with DNA sequences have been used to successfully untangle evolutionary relationships in several groups of organisms. Published mitogenomes of two caryophylliid genera (Desmophyllum and Solenosmilia) present a transposition of the gene block containing cob, nad2, and nad6, which is located between nad5 5' exon and trnW, while that of Polycyathus chaishanensis presents the same gene order as the majority of scleractinian corals. In molecular-based evolutionary reconstructions, caryophylliids that have the mitochondrial gene rearrangement were recovered as a monophyletic lineage ("true" caryophylliids), while members of the genus Polycyathus were placed in a different position. In this study, additional mitogenomes of this family were assembled and included in evolutionary reconstructions of Scleractinia in order to improve our understanding on whether the mitogenome gene rearrangement is limited to and, therefore, could be a synapomorphy of the actual members of Caryophylliidae. Specimens of Caryophyllia scobinosa, Premocyathus sp., Heterocyathus sulcatus, and Trochocyathus caryophylloides, as well as Desmophyllum pertusum and Solenosmilia variabilis from the Southwest Atlantic were sequenced using Illumina platforms. Then, mitochondrial genomes were assembled and annotated, and nuclear datasets were recovered in-silico from assembled contigs using a previously published set of baits. Evolutionary reconstructions were performed using mitochondrial and nuclear datasets and based on Maximum Likelihood and Bayesian Inference. Obtained mitogenomes are circular and range between 15,816 and 18,225 bp in size and from 30.76% to 36.63% in GC content. The gene rearrangement is only seen in C. scobinosa, D. pertusum, Premocyathus sp., and S. variabilis, which were recovered as a monophyletic clade in both mitochondrial and nuclear phylogenies. On the other hand, the "caryophylliids" with the canonical mitogenome gene order were not recovered within this clade. Differences in features of the skeleton of "true" caryophylliids in comparison to traditional members of the family were observed and offer further support that the gene rearrangement might be seen as a synapomorphy of family Caryophylliidae.

Establishing a baseline for a national paediatric antimicrobial stewardship programme.

BACKGROUND: The majority of antimicrobial stewardship programmes focus on prescribing in adult populations; however, there is a recognized need for targeted paediatric antimicrobial stewardship to improve the quality and safety of prescribing amongst this patient group. OBJECTIVES: To describe the current epidemiology of antimicrobial prescribing in paediatric inpatient populations in Scotland to establish a baseline of evidence and identify priority areas for quality improvement to support a national paediatric antimicrobial stewardship programme. METHODS: A total of 559 paediatric inpatients were surveyed during the Scottish national point prevalence survey of healthcare-associated infections and antimicrobial prescribing, 2016. The prevalence of antimicrobial prescribing was calculated and characteristics of antimicrobial prescribing were described as proportions and compared between specialist hospitals and paediatric wards in acute hospitals. RESULTS: Prevalence of antimicrobial use in paediatric inpatients was 35.4% (95% CI = 31.6%-39.4%). Treatment of community- and hospital-acquired infections accounted for 47.1% and 20.7% of antimicrobial use, respectively, with clinical sepsis being the most common diagnosis and gentamicin the most frequently prescribed antimicrobial for the treatment of infection. The reason for prescribing was documented in the notes for 86.5% of all prescriptions and, of those assessed for compliance against local policy, 92.9% were considered compliant. CONCLUSIONS: Data from national prevalence surveys are advantageous when developing antimicrobial stewardship programmes. Results have highlighted differences in the prescribing landscape between paediatric inpatient populations in specialist hospitals and acute hospitals, and have informed priorities for the national antimicrobial stewardship programme, which reinforces the need for a targeted paediatric antimicrobial stewardship programme.

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

Corticosteroids for treating nerve damage in leprosy.

BACKGROUND: Leprosy causes nerve damage that can result in nerve function impairment and disability. Corticosteroids are commonly used for treating nerve damage, although their long-term effect is uncertain. This is an update of a review first published in 2007, and previously updated in 2009 and 2011. OBJECTIVES: To assess the effects of corticosteroids on nerve damage in leprosy. SEARCH METHODS: On 16 June 2015, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, and LILACS. We also checked clinical trials registers and contacted trial authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of corticosteroids for nerve damage in leprosy. The comparators were no treatment, placebo treatment, or a different corticosteroid regimen. DATA COLLECTION AND ANALYSIS: The primary outcome was improvement in nerve function after one year. Secondary outcomes were change in nerve pain, limitations in activities of daily living, limitations in participation, and adverse events. Two review authors independently extracted data and assessed trial quality. When data were lacking, we contacted trial authors for additional information. MAIN RESULTS: We included five RCTs involving 576 people. The trials were largely at low risk of bias, but we considered the quality of the evidence from these trials as moderate to low, largely due to imprecision from small sample sizes. Two out of the five trials reported on improvement in nerve function at one year. These two trials compared prednisolone with placebo. One trial, with 84 participants, treated mild sensory impairment of less than six months' duration, and the other, with 95 participants, treated nerve function impairment of 6 to 24 months' duration. There was no significant difference in nerve function improvement after 12 months between people treated with prednisolone and those treated with placebo. Adverse events were not reported significantly more often with corticosteroids than with placebo. The other three trials did not report on the primary outcome measure. One (334 participants) compared three corticosteroid regimens for severe type 1 reactions. No serious side effects of steroids were reported in any participant during the follow-up period. Another trial (21 participants) compared low-dose prednisone with high-dose prednisone for ulnar neuropathy. Two participants on the higher dose of prednisone reported adverse effects. The last (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone. The trial found no significant differences between the groups in the occurrence of adverse events. AUTHORS' CONCLUSIONS: Corticosteroids are used for treating acute nerve damage in leprosy, but moderate-quality evidence from two RCTs treating either longstanding or mild nerve function impairment did not show corticosteroids to have a superior effect to placebo on nerve function improvement. A third trial showed significant benefit from a five-month steroid regimen over a three-month regimen in terms of response to treatment (need for additional corticosteroids). Further RCTs are needed to establish optimal corticosteroid regimens and to examine the efficacy and safety of adjuvant or new therapies for treating nerve damage in leprosy. Future trials should address non-clinical aspects, such as costs and impact on quality of life, which are highly relevant indicators for both policymakers and participants.

A pilot validation in 10 European Union Member States of a point prevalence survey of healthcare-associated infections and antimicrobial use in acute hospitals in Europe, 2011.

We present a pilot validation study performed on 10 European Union (EU) Member States, of a point prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in Europe in 2011 involving 29 EU/European Economic Area (EEA) countries and Croatia. A total of 20 acute hospitals and 1,950 patient records were included in the pilot study, which consisted of validation and inter-rater reliability (IRR) testing using an in-hospital observation approach. In the validation, a sensitivity of 83% (95% confidence interval (CI): 79­87%) and a specificity of 98% (95% CI: 98­99%) were found for HAIs. The level of agreement between the primary PPS and validation results were very good for HAIs overall (Cohen's κappa (κ):0.81) and across all the types of HAIs (range: 0.83 for bloodstream infections to 1.00 for lower respiratory tract infections). Antimicrobial use had a sensitivity of 94% (95% CI: 93­95%) and specificity of 97% (95% CI: 96­98%) with a very good level of agreement (κ:0.91). Agreement on other demographic items ranged from moderate to very good (κ: 0.57­0.95): age (κ:0.95), sex (κ: 0.93), specialty of physician (κ: 0.87) and McCabe score (κ: 0.57). IRR showed a very good level of agreement (κ: 0.92) for both the presence of HAIs and antimicrobial use. This pilot study suggested valid and reliable reporting of HAIs and antimicrobial use in the PPS dataset. The lower level of sensitivity with respect to reporting of HAIs reinforces the importance of training data collectors and including validation studies as part of a PPS in order for the burden of HAIs to be better estimated.

Definitions of progression in chronic kidney disease--predictors and relationship to renal replacement therapy in a population cohort with a 6 year follow-up.

BACKGROUND: Chronic kidney disease (CKD) is common, important and associated with increased healthcare needs due to CKD progression. Definitions of renal disease progression are multiple, and not always comparable. A measure of 'progression' directly comparable with renal replacement therapy (RRT) initiation would identify 'progressors' in research and for healthcare planning. METHODS: The Grampian Laboratory Outcomes Morbidity and Mortality Study (GLOMMS-I) is a community cohort with CKD from 2003, followed up to June 2009 for (i) RRT initiation and (ii) 'progression': sustained reduction in estimated glomerular filtration rate (eGFR) by 15 mL/min/1.73 m2 (equivalent to CKD stage change), or to <10 mL/min/1.73 m2, whichever occurs first. Predictors were baseline demographics and comorbidity. The use of the Kidney Disease: Improving Global Outcomes-2012 progression definition was also explored. RESULTS: Two thousand two hundred and eighty-nine and 1044 had Stage 3 and 4 CKD, 44% were males. Overall, RRT initiation and progression rates were 0.97 and 3.50 per 100 patient-years (py). Females had significantly lower progression and RRT initiation rates. The progression rate was not dependent on CKD stage [incidence rate ratio (IRR) for Stage 4 (versus Stage 3) 0.9 (95% CI 0.8-1.2)], whereas the RRT initiation rate was [IRR 5.6 (95% CI 3.8-8.2)]. Increased proteinuria was associated with both greater RRT initiation and progression rates. CONCLUSIONS: Progression and RRT initiation rate ratios allow comparison of predictors of these outcomes. Higher rates of both in males suggest that greater RRT initiation rate is biological rather than due to preferential treatment. Similar progression but very different RRT initiation rates in Stage 3 and 4 CKD suggests that CKD stage effect on RRT initiation is a function of endpoint proximity rather than faster renal function deterioration.

Role of contact tracing and prevention strategies in the interruption of leprosy transmission.

The global prevalence of leprosy has declined from 5.2 million in the 1980 s to 200,000 today. However, the new case detection rate remains high: over the last 8 years, around 220,000-250,000 people have been diagnosed with leprosy each year. In June 2013, an international meeting was organised by the Novartis Foundation for Sustainable Development in Geneva, Switzerland,2 with the objective of discussing the feasibility of interrupting the transmission of leprosy. The group of physicians, epidemiologists and public health professionals concluded that a successful programme would require early diagnosis and prompt multidrug therapy (MDT) for all patients, tracing and post-exposure prophylaxis (PEP) for contacts of patients newly diagnosed with leprosy, improvements in diagnostic tools, as well as strict epidemiological surveillance and response systems to monitor progress. As a follow-up, a second expert group meeting was convened by the Novartis Foundation in January 2014 in Zurich, Switzerland, with the objective of reviewing the evidence for chemoprophylaxis in contacts and high-risk communities. The meeting also considered the definitions of 'contacts' and 'contact tracing', discussed alternative prophylaxis regimens, preliminary findings of operational pilot projects on PEP in Indonesia, as well as the development of diagnostic tools, and identified the priority questions for operational research in leprosy transmission. The meeting outlined how contact tracing and chemoprophylaxis programmes can be implemented to interrupt leprosy transmission. The expert panel reached the following conclusions: Chemoprophylaxis with single-dose rifampicin (SDR) is efficacious in reducing the risk of developing leprosy, although the protective effect appears to be smaller in contacts closer to the index patient than in more distant contacts.3 SDR can be targeted to contacts or implemented as community mass prophylaxis in certain circumstances; the preferred approach depends on local factors, such as the case detection rate, the level of community stigma against leprosy, and the degree of access to healthcare for patients and contacts. Alternative prophylaxis regimens and the role of post-exposure immunoprophylaxis need to be further investigated. Contact tracing combined with PEP across very diverse settings offers protection rates similar to those reported in controlled trials. For high-incidence pockets ('hotspots') or remote or confined high-incidence populations ('hotpops'), blanket administration of PEP may be a better option. Implementation of contact-tracing programmes is feasible and cost-effective, particularly in high-risk groups, but it should be integrated into local healthcare services to ensure their long-term sustainability. Funding and support must be maintained after an initial pilot has finished. New programmes for contact tracing need effective surveillance systems to enable appropriate follow-up and outcome evaluation. The Novartis Foundation and Netherlands Leprosy Relief (NLR) are currently developing and implementing a large international programme to demonstrate the feasibility, acceptability, cost-effectiveness and real-world efficacy of PEP as a strategy to interrupt leprosy transmission, in six pilot projects in Asia, Africa and South America. These new pilot projects will be developed together with the local health authorities, healthcare workers, communities and patients, in order to create local ownership from the outset. The pilots should aim to be scalable and sustainable, and should therefore include an objective outcome assessment. Local ownership ensures that locally appropriate language and definitions of contacts are used in each of the pilots. A test to identify subclinical disease and distinguish M. leprae exposure from infection would facilitate early and appropriate therapy (with PEP or MDT). The identification and validation of new, sensitive biomarkers for M. leprae infection and exposure may allow better targeting of PEP to those contacts at highest risk of developing leprosy.

Advancing outbreak simulation training: a collaborative pilot study for dual-specialty medical trainees and infection prevention and control professionals.

BACKGROUND: In response to identified gaps in infection prevention and control (IPC) training within Scotland, a Short Life Working Group initiated an innovative outbreak simulation training programme. AIM: To enhance the knowledge and confidence of medical microbiology and infectious diseases trainees and IPC professionals in managing healthcare-associated infection (HAI) outbreaks, employing the National Infection Prevention and Control Manual guidelines. METHODS: Participants completed prerequisite online training in epidemiology and surveillance before engaging in a meticulously crafted vancomycin-resistant enterococci outbreak simulation, which mirrored a real-life incident and adhered to the standards set by the Association for Simulated Practice in Healthcare. The programme incorporated Kolb's experiential learning cycle, fostering an authentic and engaging learning environment. A total of 41 individuals participated in the synchronous online training phase, with eight individuals involved in the pilot outbreak simulation. Evaluation of the training's efficacy followed Kirkpatrick's model, combining quantitative (five-point Likert scales) and qualitative (open-ended questions and participant reflections) data collection methods. FINDINGS: Results demonstrated significant improvements in participants' knowledge, skills, and confidence in outbreak management. Feedback highlighted the realism and educational value of the simulation, with 100% agreement on its efficacy in enhancing outbreak management capabilities. CONCLUSION: The success of this pilot study underscores the potential of simulation training in IPC and paves the way for broader implementation. It emphasizes the effectiveness of structured, experiential learning in equipping healthcare professionals with practical skills and confidence for managing complex HAI outbreaks, contributing to a more competent and prepared workforce.

300 million years apart: the extreme case of macromorphological skeletal convergence between deltocyathids and a turbinoliid coral (Anthozoa, Scleractinia).

The integration of morphological and molecular lines of evidence has enabled the family Deltocyathidae to be erected to accommodate Deltocyathus species that were previously ascribed to the family Caryophylliidae. However, although displaying the same morphological characteristics as other species of Deltocyathus , molecular data suggested that D. magnificus was phylogenetically distant from Deltocyathidae, falling within the family Turbinoliidae instead. To elucidate the enigmatic evolutionary history of this species and skeletal microstructural features, the phylogenetic relationships of Deltocyathidae and Turbinoliidae were investigated using nuclear ultraconserved and exon loci and complete mitochondrial genomes. Both nuclear and mitochondrial phylogenomic reconstructions confirmed the position of D. magnificus within turbinolids. Furthermore, a novel mitochondrial gene order was uncovered for Deltocyathidae species. This gene order was not present in Turbinoliidae or in D. magnificus that both have the scleractinian canonical gene order, further indicating the taxonomic utility of mitochondrial gene order. D. magnificus is therefore formally moved to the family Turbinoliidae and accommodated in a new genus (Dennantotrochus Kitahara, Vaga & Stolarski, gen. nov.). Surprisingly, turbinolids and deltocyathids do not differ in microstructural organisation of the skeleton that consists of densely packed, individualised rapid accretion deposits and thickening deposits composed of fibres perpendicular to the skeleton surface. Therefore, although both families are clearly evolutionarily divergent, macromorphological features indicate a case of skeletal convergence while these may still share conservative biomineralisation mechanisms. ZooBank: urn:lsid:zoobank.org:pub:5F1C0E25-3CC6-4D1F-B1F0-CD9D0014678E.

Reduced lung function due to biomass smoke exposure in young adults in rural Nepal.

This study aimed to assess the effects of biomass smoke exposure on lung function in a Nepalese population, addressing some of the methodological issues seen in previous studies. We carried out a cross-sectional study of adults in a population exposed to biomass smoke and a non-exposed population in Nepal. Questionnaire and lung function data were acquired along with direct measures of indoor and outdoor air quality. Ventilatory function (forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and forced expiratory flow at 25-75% of FVC) was significantly reduced in the population using biomass across all age groups compared to the non-biomass-using population, even in the youngest (16-25 yrs) age group (mean FEV(1) (95% CI) 2.65 (2.57-2.73) versus 2.83 (2.74-2.91) L; p=0.004). Airflow obstruction was twice as common among biomass users compared with liquefied petroleum gas users (8.1% versus 3.6%; p<0.001), with similar patterns for males (7.4% versus 3.3%; p=0.022) and females (10.8% versus 3.8%; p<0.001), based on the lower limit of normal. Smoking was a major risk factor for airflow obstruction, but biomass exposure added to the risk. Exposure to biomass smoke is associated with deficits in lung function, an effect that can be detected as early as the late teenage years. Biomass smoke and cigarette smoke have additive adverse effects on airflow obstruction in this setting.

Chronic kidney disease, a useful trigger for proactive primary care? Mortality results from a large U.K. cohort.

BACKGROUND: Much of the emphasis for primary care management of chronic kidney disease (CKD) has focused on cardiovascular risk; however, many patients die of other causes. Aim. In order to guide future primary care management of CKD, we report the causes of death from a large U.K. CKD cohort linked to health care administrative data. DESIGN, SETTING AND METHODS: The Grampian Laboratory Outcomes Mortality and Morbidity Study (GLOMMS-1) is a community cohort of people with established CKD, identified in 2003 and followed up for 6 years. Causes of death were available from death certificates. The relative likelihood of different causes of death was compared to the general population. RESULTS: When standardized for age and sex, mortality was 4.7 (95% confidence interval 4.5-4.9) times higher in GLOMMS-1 than the general population. Non-cardiovascular diseases accounted for 1076 (50.9%) of deaths, 3.7 times more common than in the age- and sex-matched general population. For those with stages 3 and 4 CKD, without cardiovascular disease at baseline, a non-cardiovascular cause accounted for almost two-thirds of deaths. In those 75 years and older, dementia and falls were among the main non-cardiovascular causes of death. CONCLUSIONS: Mortality in those with CKD is high, with non-cardiovascular diseases accounting for more than half of all deaths. While there is evidence that intervention may benefit those at risk of cardiovascular death, most of the non-cardiovascular causes of death identified were not readily amenable to prevention. A mechanism to identify which patients may benefit from intervention to prevent cardiovascular disease or renal disease progression is needed.

A revision of the genus Thouarella Gray, 1870 (Octocorallia: Primnoidae), including an illustrated dichotomous key, a new species description, and comments on Plumarella Gray, 1870 and Dasystenella, Versluys, 1906.

A comprehensive revision of the genus Thouarella is presented. Thirty-five holotypes of the 38 nominal Thouarella species, two varieties, and one form were examined. The number of original Thouarella species has been reduced to 25, mostly through synonymy or new genus combinations. In the process several new species have also been identified, one of which is described here as Thouarella parachilensis nov. sp. The genus is split into two groups based on polyp arrangement: Group 1 with isolated polyps and Group 2 with polyps in pairs or whorls. An illustrated dichotomous key and detailed character table of the 25 Thouarella species are presented alongside an up-to-date account of all species described in the 19th and 20th centuries and summaries of the few described from 2000 onwards. We propose that Thouarella longispinosa is synonymous with Dasystenella acanthina, T. versluysi with T. brucei, and, T. tenuisquamis, T. flabellata, and T. carinata are synonymous with T. laxa. Lastly, we propose that T. bayeri and T. undulata be placed in Plumarella and support recent suggestions that T. alternata, T. recta, T. superba, and T. diadema are also Plumarella.

Translating chronic kidney disease epidemiology into patient care--the individual/public health risk paradox.

BACKGROUND: Applying the Kidney Disease Outcomes Quality Initiative definitions of chronic kidney disease (CKD), it appears that CKD is common. The increased recognition of CKD has brought with it the clinical challenge of translating into practice the implications for the patient and for service planning. To understand the clinical relevance and translate that into information to support individual patient care and service planning, we explored clinical outcomes in a large British CKD cohort, identified through routine opportunistic testing, with a 6-year follow-up (≈ 13,000 patient-years). METHODS: A cohort had previously been identified with CKD-sustained reduced eGFR over at least 3 months and case note review. Six-year (13,339 patient-years) follow-up for renal replacement therapy (RRT) initiation and death was achieved through data linkage. Age- and sex-specific mortality rates were compared to the general population. RESULTS: Of 3414 individuals (most Stage 3b-5), median age 78.6 years, followed for 13 339 patient-years, 170 (5%) initiated RRT and 2024 (59%) died without initiating RRT. RRT initiation rates decreased with age from 14.33 to 0.65 per 100 patient-years among those aged 15-25 and 75-85 years at baseline but the actual numbers initiating RRT increased from 6 to 34, respectively. RRT initiation rates were lower for female sex, absence of macroalbuminuria and less advanced CKD stage. Mortality rates increased with age from 2 to 34 per 100 patient-years for those aged 15-45 and > 85 years at baseline, an excess of 2 and 17 per 100 patient-years over that of the general population, respectively. However, the increase in relative risk was 19-fold for those aged 15-45 years and just 2-fold in those > 85 years. These data have been converted into simple tools for considering individual patients' risk and informing service planning. CONCLUSIONS: The contrast between relative and absolute risk for both RRT initiation and mortality by age group illustrates the difficulties for planning services. The challenge that now faces clinicians is how to appropriately identify which elderly patients with CKD are at high risk of poor outcome.

Social care and support for elderly men and women in an urban and a rural area of Nepal.

This study has aimed to describe the care and support for urban and rural elderly people of Bhaktapur district, Nepal. Efforts were made to identify the feeling of some features of general well-beings associated to mental health, person responsible for care and support, capability to perform daily routine activities, sources of finance and ownership to the property. More than half of the respondents were found having single or multiple features of loneliness, anxiety, depression and insomnia. The rate of point prevalence loneliness was found higher in the above 80 years of age, urban respondents. Almost 9 in 10 respondents were capable themselves to dress, walk and maintain personal hygiene and majority of them were assisted by spouse, son/daughter-in-laws. Family support was common sources of income and ownership to the property was absolutely high.

Assessing and improving adherence with multidrug therapy.

INTRODUCTION: Adherence with multidrug therapy (MDT) in the treatment of leprosy is important to minimise the risk of relapse and avoid the emergence of drug resistance. Adherence is defined as the extent to which the patient's behaviour matches recommendations from the prescriber. This paper reviews the methods for assessing adherence with MDT in leprosy, and community approaches to improving adherence based on evidence from the treatment of tuberculosis (TB) and HIV, as well as leprosy. METHODS: To identify and summarise the available literature regarding the assessment of treatment regularity in leprosy, a literature search of MEDLINE was conducted using the following search terms: 'leprosy' AND ('adherence' OR 'compliance' OR 'concordance'). To identify evidence for interventions that have involved community members in HIV, TB or leprosy adherence support, a literature search was conducted using the key terms and medical subject headings 'treatment or adherence' 'community,' 'HIV, TB or Leprosy' and 'low and middle income countries' combined using Boolean operators. RESULTS: Leprosy programmes routinely use defaulting and treatment completion as proxy measures of adherence as recommended by the WHO global strategy. However, a number of other methods have been used to assess adherence including questionnaires, pill counts, as well as direct measures based on testing urine for the presence of dapsone. Direct methods were extensively used during the dapsone mono-therapy era but there is little evidence of their use in MDT. Use of multiple methods of assessing adherence improves the accuracy and reliability of the results. Community activities in TB and HIV such as variants of treatment observation, and/or wider programmes of counselling or direct support to the patient or their family or to increase community or social support were shown to improve treatment outcomes. Outcomes evaluated included treatment default and completion, clinical indicators, and adherence (pill-count, self report). CONCLUSIONS: Adherence is very important in leprosy and regular assessment of medication adherence together with constructive feedback and counselling of patients is likely to be beneficial. Leprosy programme can learn from adherence support interventions developed by both TB and HIV programmes.

Physical activity attitudes, intentions and behaviour among 18-25 year olds: a mixed method study.

BACKGROUND: Young people (18-25 years) during the adolescence/adulthood transition are vulnerable to weight gain and notoriously hard to reach. Despite increased levels of overweight/obesity in this age group, physical activity behaviour, a major contributor to obesity, is poorly understood. The purpose of this study was to explore physical activity (PA) behaviour among 18-25 year olds with influential factors including attitudes, motivators and barriers. METHODS: An explanatory mixed method study design, based on health Behaviour Change Theories was used. Those at university/college and in the community, including those Not in Education, Employment or Training (NEET) were included. An initial self reported quantitative questionnaire survey underpinned by the Theory of Planned Behaviour and Social Cognitive Theory was conducted. 1313 questionnaires were analysed. Results from this were incorporated into a qualitative phase also grounded in these theories. Seven focus groups were conducted among similar young people, varying in education and socioeconomic status. Exploratory univariate analysis was followed by multi staged modelling to analyse the quantitative data. 'Framework Analysis' was used to analyse the focus groups. RESULTS: Only 28% of 18-25 year olds achieved recommended levels of PA which decreased with age. Self-reported overweight/obesity prevalence was 22%, increasing with age, particularly in males. Based on the statistical modelling, positive attitudes toward PA were strong predictors of physical activity associated with being physically active and less sedentary. However, strong intentions to do exercise, was not associated with actual behaviour. Interactive discussions through focus groups unravelled attitudes and barriers influencing PA behaviour. Doing PA to feel good and to enjoy themselves was more important for young people than the common assumptions of 'winning' and 'pleasing others'. Further this age group saw traditional health promotion messages as 'empty' and 'fear of their future health' was not a motivating factor to change current behaviour. CONCLUSION: 18-25 year olds are a difficult group to reach and have low levels of PA. Factors such as, 'enjoyment', 'appearance 'and 'feeling good' were deemed important by this specific age group. A targeted intervention incorporating these crucial elements should be developed to improve and sustain PA levels.

Potential effect of the World Health Organization's 2011-2015 global leprosy strategy on the prevalence of grade 2 disability: a trend analysis.

OBJECTIVE: To assess different countries' chances of attaining the 2011-2015 global leprosy target set by the World Health Organization (WHO) and to assess the strategy's effect on the prevalence of grade 2 disability (G2D). METHODS: Trends in G2D rate were analysed for Brazil, China, India and Thailand and figures were compared with the WHO target: a 35% decrease by 2015 relative to the 2010 baseline. To estimate the prevalence of G2D in 2015 and 2035 for each country three assumptions were made: (i) maintenance of the current trend; (ii) attainment of the WHO target, and (iii) reduction of G2D by 50% every 5 years relative to 2010. FINDINGS: Since 1995, the G2D rate has decreased every 5 years in Brazil, China, India and Thailand by 12.7% (95% confidence interval, CI: 6.6-18.3), 7.7% (95% CI: 1.1-12.8), 53.7% (95% CI: 38.1-65.4) and 35.9% (95% CI: 23.4-46.3), respectively. New cases with G2D detected after 2010 will contribute 15% (Brazil), 3% (China), 2.5% (India) and 4% (Thailand) to the total prevalence of G2D in 2015. If no policies are changed, between 2015 and 2035, the prevalence of G2D will decrease by more than half in China, India and Thailand, and by 16% in Brazil. CONCLUSION: The implications of attaining the WHO target are different for each country and using indicators other than G2D prevalence will help monitor progress. The strategy will not immediately reduce the prevalence of G2D, but if it is applied consistently over the next 25 years, its long-term effect can be substantial.

Reasons for non- use of condoms and self- efficacy among female sex workers: a qualitative study in Nepal.

BACKGROUND: Heterosexual contact is the most common mode of transmission of sexually transmitted infections (STIs) including Human Immunodeficiency Virus (HIV) in Nepal and it is largely linked to sex work. We assessed the non-use of condoms in sex work with intimate sex partners by female sex workers (FSWs) and the associated self-efficacy to inform the planning of STI/HIV prevention programmes in the general population. METHODS: This paper is based on a qualitative study of Female Sex Workers (FSWs) in Nepal. In-depth interviews and extended field observation were conducted with 15 FSWs in order to explore issues of safe sex and risk management in relation to their work place, health and individual behaviours. RESULTS: The main risk factor identified for the non-use of condoms with intimate partners and regular clients was low self efficacy. Non-use of condoms with husband and boyfriends placed them at risk of STIs including HIV. In addition to intimidation and violence from the police, clients and intimate partners, clients' resistance and lack of negotiation capacity were identified as barriers in using condoms by the FSWs. CONCLUSION: This study sheds light on the live and work of FSWs in Nepal. This information is relevant for both the Government of Nepal and Non Governmental Organisations (NGO) to help improve the position of FSWs in the community, their general well-being and to reduce their risks at work.

Utilisation of sexual health services by female sex workers in Nepal.

BACKGROUND: The Nepal Demographic Health Survey (NDHS) in 2006 showed that more than half (56%) of the women with sexually transmitted infections (STIs), including HIV, in Nepal sought sexual health services. There is no such data for female sex workers (FSWs) and the limited studies on this group suggest they do not even use routine health services. This study explores FSWs use of sexual health services and the factors associated with their use and non-use of services. METHODS: This study aimed to explore the factors associated with utilisation of sexual health services by FSWs in the Kathmandu Valley of Nepal, and it used a mixed-method approach consisting of an interviewer administered questionnaire-based survey and in-depth interviews. RESULTS: The questionnaire survey, completed with 425 FSWs, showed that 90% FSWs self-reported sickness, and (30.8%) reported symptoms of STIs. A quarter (25%) of those reporting STIs had never visited any health facilities especially for sexual health services preferring to use non-governmental clinics (72%), private clinics (50%), hospital (27%) and health centres (13%). Multiple regression analysis showed that separated, married and street- based FSWs were more likely to seek health services from the clinics or hospitals. In- depth interviews with 15 FSWs revealed that FSWs perceived that personal, structural and socio-cultural barriers, such as inappropriate clinic opening hours, discrimination, the judgemental attitude of the service providers, lack of confidentiality, fear of public exposure, and higher fees for the services as barriers to their access and utilisation of sexual health services. CONCLUSION: FSWs have limited access to information and to health services, and operate under personal, structural and socio-cultural constraints. The 'education' to change individual behaviour, health worker and community perceptions, as well as the training of the health workers, is necessary.