Realistic Food-Based Approaches Alone May Not Ensure Dietary Adequacy for Women and Young Children in South-East Asia.

Objectives Micronutrient deficiencies, in southeast Asia (SE Asia), remain a public health challenge. We evaluated whether promoting the consumption of locally available nutritious foods, which is a low-risk micronutrient intervention, alone can ensure dietary adequacy, for women of reproductive age and 6-23 m old children. Methods Representative dietary data from Cambodia, Indonesia, Lao PDR, Thailand and Vietnam were analysed using linear programming analysis to identify nutrients that are likely low in personal food environments (problem nutrients), and to formulate food-based recommendations (FBRs) for three to six target populations per country. Results The number of problem nutrients ranged from zero for 12-23 m olds in Indonesia, Thailand and Vietnam to six for pregnant women in Cambodia. The FBRs selected for each target population, if adopted, would ensure a low percentage of the population was at risk of inadequate intakes for five to ten micronutrients, depending on the country and target population. Of the 11 micronutrients modelled, requirements for iron, calcium and folate were most difficult to meet (≥ 10 of the 24 target populations), using FBRs alone. The number of individual FBRs selected per set, for each target population, ranged from three to eight; and often included meat, fish or eggs, liver/organ meats, vegetables and fruits. Conclusions for practice Intervention strategies need to increase access to nutritious foods, including products fortified with micronutrients, in SE Asia, when aiming to ensure dietary adequacy for most individuals in the population.

Bladder dysfunction and hypertension in children with Guillain-Barre syndrome.

BACKGROUND: Guillain-Barre syndrome (GBS) causes acute motor, sensory and autonomic dysfunction. There is a relative paucity of published data regarding the autonomic features of GBS. The aims of this study were to describe the incidence, management and outcome of bladder dysfunction and hypertension in GBS and to ascertain whether these features relate to muscle weakness severity. CASE-DIAGNOSIS/TREATMENT: Twenty-seven patients with a median (interquartile range) age of 5.7 (3.5-8.4) years were included, of whom 18 (67%) were male and 14 (52%) had autonomic dysfunction. One patient presented with and three subsequently developed urinary retention necessitating catheterisation for a median of 7.5 (7-14.5) days. Univariate analysis demonstrated that urinary retention was associated with weakness in all four limbs [retention: MRC muscle grade 2 (2-2.75); no retention: MRC grade 4 (3-4); p = 0.02], possibly reflecting more severe disease. Patients with hypertension (12 patients, 44%) had a longer hospital stay [median 32.5 (15.5-53.5) days; rho = 0.65; p = 0.02], and those with worse muscle weakness required more anti-hypertensive medications (upper limb rho = -0.71, p = 0.03; lower limb rho = -0.72, p = 0.03]. The majority of blood pressure treatments involved calcium channel and beta blockers. CONCLUSION: In children with GBS, bladder dysfunction and hypertension are common. The presence of severe muscle weakness may predict those at greatest risk of these complications.

Urine biomarkers for monitoring juvenile lupus nephritis: a prospective longitudinal study.

BACKGROUND: In juvenile-onset systemic lupus erythematosus (JSLE), renal involvement (lupus nephritis) is frequently seen and can result in long-term morbidity. This prospective longitudinal study aimed to identify the utility of standard and/or novel biomarkers for monitoring and predicting lupus nephritis in a real world setting. METHODS: Using an unselected JSLE cohort, urine samples were collected during routine clinical review. Protein concentrations of urinary monocyte chemo-attractant protein 1 (uMCP1) and neutrophil gelatinase-associated lipocalin (uNGAL) were analysed along with standard disease activity markers, and were compared with current and subsequent disease activity. RESULTS: JSLE patients (n = 64; median age 14.1 years) were seen at 3 (interquartile range: 2-5) clinical reviews over 364 (182-532) days. Multivariate analysis demonstrated uMCP1 and serum C3 as independent variables (p < 0.001) for active renal disease at the time of the current review. uMCP1 was an excellent predictor of improved renal disease over time (AUC: 0.81; p = 0.013). uNGAL was a good predictor of worsened renal disease activity (AUC 0.76; p = 0.04) over time. CONCLUSION: Biomarkers (uMCP1, serum C3) can indicate current renal involvement in JSLE, whilst uMCP1 and uNGAL are able to predict subsequent renal disease activity changes. Moving towards biomarker-led monitoring may improve the renal outcome for our patients.

RET overexpression leads to increased brain metastatic competency in luminal breast cancer.

BACKGROUND: Breast cancer brain metastasis is a rising occurrence, necessitating a better understanding of the mechanisms involved for effective management. Breast cancer brain metastases diverge notably from the primary tumor, with gains in kinase and concomitant losses of steroid signaling observed. In this study, we explored the role of the kinase receptor RET in promoting breast cancer brain metastases and provide a rationale for targeting this receptor. METHODS: RET expression was characterized in a cohort of patients with primary and brain metastatic tumors. RET functionality was assessed using pharmacological inhibition and gene silencing in patient-derived brain metastatic tumor explants and in vivo models, organoid models, and brain organotypic cultures. RNA sequencing was used to uncover novel brain metastatic relevant RET mechanisms of action. RESULTS: A statistically significant enrichment of RET in brain metastases was observed in estrogen receptor-positive breast cancer, where it played a role in promoting cancer cell adhesion, survival, and outgrowth in the brain. In vivo, RET overexpression enhanced brain metastatic competency in patient-derived models. At a mechanistic level, RET overexpression was found to enhance the activation of gene programs involved in cell adhesion, requiring EGFR cooperation to deliver a pro-brain metastatic phenotype. CONCLUSION: Our results illustrate, for the first time, the role of RET in regulating colonization and outgrowth of breast cancer brain metastasis and provide data to support the use of RET inhibitors in the management strategy for patients with breast cancer brain metastases.

The effectiveness of mobile-health technology-based health behaviour change or disease management interventions for health care consumers: a systematic review.

BACKGROUND: Mobile technologies could be a powerful media for providing individual level support to health care consumers. We conducted a systematic review to assess the effectiveness of mobile technology interventions delivered to health care consumers. METHODS AND FINDINGS: We searched for all controlled trials of mobile technology-based health interventions delivered to health care consumers using MEDLINE, EMBASE, PsycINFO, Global Health, Web of Science, Cochrane Library, UK NHS HTA (Jan 1990-Sept 2010). Two authors extracted data on allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. We calculated effect estimates and used random effects meta-analysis. We identified 75 trials. Fifty-nine trials investigated the use of mobile technologies to improve disease management and 26 trials investigated their use to change health behaviours. Nearly all trials were conducted in high-income countries. Four trials had a low risk of bias. Two trials of disease management had low risk of bias; in one, antiretroviral (ART) adherence, use of text messages reduced high viral load (>400 copies), with a relative risk (RR) of 0.85 (95% CI 0.72-0.99), but no statistically significant benefit on mortality (RR 0.79 [95% CI 0.47-1.32]). In a second, a PDA based intervention increased scores for perceived self care agency in lung transplant patients. Two trials of health behaviour management had low risk of bias. The pooled effect of text messaging smoking cessation support on biochemically verified smoking cessation was (RR 2.16 [95% CI 1.77-2.62]). Interventions for other conditions showed suggestive benefits in some cases, but the results were not consistent. No evidence of publication bias was demonstrated on visual or statistical examination of the funnel plots for either disease management or health behaviours. To address the limitation of the older search, we also reviewed more recent literature. CONCLUSIONS: Text messaging interventions increased adherence to ART and smoking cessation and should be considered for inclusion in services. Although there is suggestive evidence of benefit in some other areas, high quality adequately powered trials of optimised interventions are required to evaluate effects on objective outcomes.

The effectiveness of mobile-health technologies to improve health care service delivery processes: a systematic review and meta-analysis.

BACKGROUND: Mobile health interventions could have beneficial effects on health care delivery processes. We aimed to conduct a systematic review of controlled trials of mobile technology interventions to improve health care delivery processes. METHODS AND FINDINGS: We searched for all controlled trials of mobile technology based health interventions using MEDLINE, EMBASE, PsycINFO, Global Health, Web of Science, Cochrane Library, UK NHS HTA (Jan 1990-Sept 2010). Two authors independently extracted data on allocation concealment, allocation sequence, blinding, completeness of follow-up, and measures of effect. We calculated effect estimates and we used random effects meta-analysis to give pooled estimates. We identified 42 trials. None of the trials had low risk of bias. Seven trials of health care provider support reported 25 outcomes regarding appropriate disease management, of which 11 showed statistically significant benefits. One trial reported a statistically significant improvement in nurse/surgeon communication using mobile phones. Two trials reported statistically significant reductions in correct diagnoses using mobile technology photos compared to gold standard. The pooled effect on appointment attendance using text message (short message service or SMS) reminders versus no reminder was increased, with a relative risk (RR) of 1.06 (95% CI 1.05-1.07, I(2) = 6%). The pooled effects on the number of cancelled appointments was not significantly increased RR 1.08 (95% CI 0.89-1.30). There was no difference in attendance using SMS reminders versus other reminders (RR 0.98, 95% CI 0.94-1.02, respectively). To address the limitation of the older search, we also reviewed more recent literature. CONCLUSIONS: The results for health care provider support interventions on diagnosis and management outcomes are generally consistent with modest benefits. Trials using mobile technology-based photos reported reductions in correct diagnoses when compared to the gold standard. SMS appointment reminders have modest benefits and may be appropriate for implementation. High quality trials measuring clinical outcomes are needed. Please see later in the article for the Editors' Summary.

Disease activity, severity, and damage in the UK Juvenile-Onset Systemic Lupus Erythematosus Cohort.

OBJECTIVE: The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. METHODS: Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE. RESULTS: Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1. CONCLUSION: The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen.

Urine biomarkers in juvenile-onset SLE nephritis.

Over 80 % of patients with juvenile-onset systemic lupus erythematosus will have renal involvement compared to 40 % with adult-onset disease. Up to 44 % of children who do have lupus nephritis (LN) progress to renal failure in early adulthood. Improved methods of detecting onset of LN would allow earlier treatment, which may prevent irreversible renal scarring and a decline in renal function. Current conventional markers of disease activity fail to adequately predict renal lupus flares and include proteinuria, complement levels, anti-double-stranded DNA antibodies and serum creatinine concentrations. Standardized histological classification is currently the gold standard for diagnosing and classifying LN, but its invasive nature limits routine use for monitoring, especially in a childhood population. Novel biomarkers need to be sensitive and specific-and preferably non-invasive and cost-effective. The most promising biomarkers in juvenile-onset LN include urinary neutrophil gelatinase associated lipocalin, monocyte chemoattractant protein 1 and transforming growth factor-beta, although many others have been identified and are under investigation. No one biomarker yet discovered is unique to LN, indicating an overlap in disease pathophysiology. It is likely that a combination of biomarkers will be required for assessing disease flare detection, response to treatment and prognostic information. Potential biomarkers require longitudinal validation in large paediatric, prospective cohorts to assess their ability to act as clinically useful adjuncts.

Interventions to improve water quality and supply, sanitation and hygiene practices, and their effects on the nutritional status of children.

BACKGROUND: Water, sanitation and hygiene (WASH) interventions are frequently implemented to reduce infectious diseases, and may be linked to improved nutrition outcomes in children. OBJECTIVES: To evaluate the effect of interventions to improve water quality and supply (adequate quantity to maintain hygiene practices), provide adequate sanitation and promote handwashing with soap, on the nutritional status of children under the age of 18 years and to identify current research gaps. SEARCH METHODS: We searched 10 English-language (including MEDLINE and CENTRAL) and three Chinese-language databases for published studies in June 2012. We searched grey literature databases, conference proceedings and websites, reviewed reference lists and contacted experts and authors. SELECTION CRITERIA: Randomised (including cluster-randomised), quasi-randomised and non-randomised controlled trials, controlled cohort or cross-sectional studies and historically controlled studies, comparing WASH interventions among children aged under 18 years. DATA COLLECTION AND ANALYSIS: Two review authors independently sought and extracted data on childhood anthropometry, biochemical measures of micronutrient status, and adherence, attrition and costs either from published reports or through contact with study investigators. We calculated mean difference (MD) with 95% confidence intervals (CI). We conducted study-level and individual-level meta-analyses to estimate pooled measures of effect for randomised controlled trials only. MAIN RESULTS: Fourteen studies (five cluster-randomised controlled trials and nine non-randomised studies with comparison groups) from 10 low- and middle-income countries including 22,241 children at baseline and nutrition outcome data for 9,469 children provided relevant information. Study duration ranged from 6 to 60 months and all studies included children under five years of age at the time of the intervention. Studies included WASH interventions either singly or in combination. Measures of child anthropometry were collected in all 14 studies, and nine studies reported at least one of the following anthropometric indices: weight-for-height, weight-for-age or height-for-age. None of the included studies were of high methodological quality as none of the studies masked the nature of the intervention from participants.Weight-for-age, weight-for-height and height-for-age z-scores were available for five cluster-randomised controlled trials with a duration of between 9 and 12 months. Meta-analysis including 4,627 children identified no evidence of an effect of WASH interventions on weight-for-age z-score (MD 0.05; 95% CI -0.01 to 0.12). Meta-analysis including 4,622 children identified no evidence of an effect of WASH interventions on weight-for-height z-score (MD 0.02; 95% CI -0.07 to 0.11). Meta-analysis including 4,627 children identified a borderline statistically significant effect of WASH interventions on height-for-age z-score (MD 0.08; 95% CI 0.00 to 0.16). These findings were supported by individual participant data analysis including information on 5,375 to 5,386 children from five cluster-randomised controlled trials.No study reported adverse events. Adherence to study interventions was reported in only two studies (both cluster-randomised controlled trials) and ranged from low (< 35%) to high (> 90%). Study attrition was reported in seven studies and ranged from 4% to 16.5%. Intervention cost was reported in one study in which the total cost of the WASH interventions was USD 15/inhabitant. None of the studies reported differential impacts relevant to equity issues such as gender, socioeconomic status and religion. AUTHORS' CONCLUSIONS: The available evidence from meta-analysis of data from cluster-randomised controlled trials with an intervention period of 9-12 months is suggestive of a small benefit of WASH interventions (specifically solar disinfection of water, provision of soap, and improvement of water quality) on length growth in children under five years of age. The duration of the intervention studies was relatively short and none of the included studies is of high methodological quality. Very few studies provided information on intervention adherence, attrition and costs. There are several ongoing trials in low-income country settings that may provide robust evidence to inform these findings.

Mathematical modeling to inform the development of national guidelines on infant feeding in Thailand.

The development of national dietary guidelines promoting healthy food choices is a public health priority in Thailand. In developing the recent national complementary feeding guidelines (CFGs) for 6- to 12-month-old children, mathematical modeling was used to inform decisions. Model parameters were derived from nationally representative dietary data and analyzed for 11 micronutrients by age group, using linear programming analysis in Optifood. Models were run to identify micronutrients whose nutrient reference values could not be met using local foods as consumed (problem nutrients), evaluate the original 2012 Thai CFGs, and predict the nutritional benefits of a specific fortified complementary food. The results identified three problem nutrients (iron, calcium, and zinc), which, for 9- to 11-month-olds, were reduced to one when the fortified food was modeled. The number of servings/week of vegetables and meat, fish or eggs were higher, and of oil and fruit were lower, in the modeled nutritionally best rather than observed diets (medians). When modeled, the original Thai CFGs were not feasible because the energy constraint was exceeded; hence, in revising them, the recommended number of servings/week of oil and fruit were reduced. This study demonstrates the advantages of using mathematical modeling, when revising national CFGs, to evaluate and improve them.

Identifying and characterizing treatment-resistant schizophrenia in observational database studies.

OBJECTIVES: Treatment-resistant schizophrenia (TRS) is clinically defined as failure to respond to two antipsychotics of adequate dose and duration. An algorithm (registry TRS) was developed, for identifying patients with TRS in claim datasets from Sweden and the United States. METHODS: Schizophrenia (SZ) patients aged ≥13 years were identified in both datasets and matched to controls. Patients were identified as having TRS by use of the registry TRS or ≥1 prescription for clozapine or use of other published criteria. The algorithm was compared for sensitivity, and patients with and without TRS were compared for psychiatric and hospital burden and Global Assessment of Functioning (GAF) scores. TRS prevalence was not assessed due to lack of clinically validated data to test the specificity of the algorithm. RESULTS: Swedish registry TRS patients ≤45 years at first SZ diagnosis had significantly lower GAF scores and earlier disease onset than non-TRS patients. SZ patients with higher psychiatric comorbidity and hospital burden were more likely identified as TRS by all algorithms. The registry algorithm was significantly more sensitive to multiple inpatient stays and all psychiatric comorbidities at identifying TRS. CONCLUSION: The registry algorithm appeared more sensitive at identifying patients with TRS, who had greater psychiatric and hospital burden.

Psychiatric and neurological symptoms in patients with Niemann-Pick disease type C (NP-C): Findings from the International NPC Registry.

Objectives: Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease that should be recognised by psychiatrists as a possible underlying cause of psychiatric abnormalities. This study describes NP-C patients who had psychiatric manifestations at enrolment in the international NPC Registry, a unique multicentre, prospective, observational disease registry. Methods: Treating physicians' data entries describing psychiatric manifestations in NPC patients were coded and grouped by expert psychiatrists. Results: Out of 386 NP-C patients included in the registry as of October 2015, psychiatric abnormalities were reported to be present in 34% (94/280) of those with available data. Forty-four patients were confirmed to have identifiable psychiatric manifestations, with text describing these psychiatric manifestations. In these 44 patients, the median (range) age at onset of psychiatric manifestations was 17.9 years (2.5-67.9; n = 15), while the median (range) age at NP-C diagnosis was 23.7 years (0.2-69.8; n = 34). Almost all patients (43/44; 98%) had an occurrence of ≥1 neurological manifestation at enrolment. Conclusions: These data show that substantial delays in diagnosis of NP-C are long among patients with psychiatric symptoms and, moreover, patients presenting with psychiatric features and at least one of cognitive impairment, neurological manifestations, and/or visceral symptoms should be screened for NP-C.

Disease burden of chronic lymphocytic leukaemia within the European Union.

OBJECTIVE: Whilst Chronic lymphocytic leukaemia (CLL) is considered a rare disease, to our knowledge, the current prevalence of CLL within the European Union (EU) member states is not published. Understanding the number of individuals with CLL is vital to assess disease burden within the wider population. METHODS: Using 2002 data from the International Agency for Research on Cancer, we estimated the number of individuals with CLL (ICD-10 C91.1) from those reported for all leukaemias (C91-95) and extrapolated the figures by the population increase within the EU between 2002 and 2006, the last year with fully updated community population estimates. One- and 5-yr partial prevalence estimates are reported (i.e. the number of individuals still living 1-5 yr post-diagnosis). We then applied proportional estimates from the literature to assess those requiring immediate treatment, those under observation and their likely progression rates. RESULTS: We found that within the 27 EU states plus Iceland, Norway and Lichtenstein, 1- and 5-yr CLL partial prevalence estimates totalled approximately 13,952 and 46,633 individuals respectively in 2006. By applying Binet staging to the 1-yr estimate, 40% of patients will be stage B/C and require immediate treatment. Thus, 5581 individuals may be treated within the first year of diagnosis. Of the 60% (8371) under observation, by 5 yr up to 33% (2763) may have more advanced disease with increased risk of mortality. CONCLUSION: Whilst CLL is a rare disease, the number of individuals burdened by the disease within the EU is considerable and thousands of patients require treatment and physician care, which has cost implications for member states.

Predicting the duration of symptoms in lower respiratory tract infection.

BACKGROUND: Acute lower respiratory tract infection (LRTI) presenting in primary care has a long natural history. Antibiotic treatment makes little or no difference to the duration of cough. Limited information is currently available regarding predictors of illness duration. AIM: To determine predictors of illness duration in acute LRTI in primary care. DESIGN OF STUDY: Secondary analysis of trial data to identify independent predictors of illness severity and duration. SETTING: Primary care. METHOD: Eight-hundred and seven patients aged 3 years and over with acute illness (21 days or less) presenting with cough as the main symptom plus at least one symptom or sign from sputum, chest pain, dyspnoea, or wheeze were recruited to the study. Main outcomes were duration of symptoms (rated at least a slight problem) and more severe symptoms (rated at least moderately bad). RESULTS: The average duration of cough (rated at least a slight problem) was 11.7 days and was shorter among children (duration -1.72 days; 95% confidence interval [CI] = -3.02 to -0.41) or in individuals with a history of fever (-1.22 days; 95% CI = -0.18 to 2.27). The duration of cough was longer among those with restricted activities on the day they saw the doctor (+0.69 days for each point of a 7-point scale). The duration of more severe symptoms was longer in those with a longer duration of symptoms prior to consultation, with a more severe cough on the day of seeing the doctor, and restriction of activities on the day of seeing the doctor. CONCLUSION: Illness duration may be predicted from a limited number of clinical symptoms and from prior history. These findings should be subjected to validation in a separate population. To minimise expectation about rapid resolution of illness, adults who have restricted activities could be advised that they are likely to experience symptoms for longer.

Outcome and severity of adult onset asthma--report from the obstructive lung disease in northern Sweden studies (OLIN).

BACKGROUND: Studies of longitudinal changes in severity and the long-term outcome of asthma in epidemiological settings are uncommon. AIM: To assess the outcome of incident asthma in a cohort of subjects who developed asthma after the age of 20 years. METHODS: This is a prospective study of the outcome of 309 subjects with incident asthma being included in a case-referent study based on all adults aged 20-60 years living in three municipalities/towns in Northern Sweden. The subjects fulfilled the criteria for incident asthma defined as onset of symptoms common in asthma within 12 months prior to the study and a verified bronchial variability. In 2003, 250 (81%) of the subjects with asthma were re-examined with structured interview, lung-function test and methacholine test. RESULTS: At follow-up, 237 (95%) subjects still had an active asthma, i.e. they had symptoms or used asthma medicines. Among those with active asthma, 65% were using inhaled cortico-steroids. Severity grading (GINA 2000) showed that 21% had mild intermittent asthma, 30% mild persistent, 44% moderate persistent, and 5% severe asthma, contrasting to 75% with moderate or severe asthma at entry. Higher age, higher BMI and low lung function were associated with greater asthma severity. Twelve subjects (5%) were in remission. Predictors for remission were non-sensitisation and a normal lung function. Age, sex, BMI, and smoking habits were not significantly different between those in remission and those not. CONCLUSIONS: Remission of adult onset asthma was low. Severity of asthma changed considerably over time, however, the overall change was towards a milder disease probably as a result of treatment.

Factors associated with mortality after an asthma admission: a national United Kingdom database analysis.

BACKGROUND: Lack of a United Kingdom (UK) fatal asthma registry has resulted in few recent analyses regarding patient characteristics, co-morbidities, and admission type in relation to mortality post an asthma admission. This study aims to report these factors in addition to season of event for the years 2000-2005 to provide data regarding asthma burden in the in-patient hospital setting. METHODS: Data were analysed from the CHKS database collated from UK National Health Service data providing 70% of in-patient coverage in the UK. Patients with admissions under ICD-10 codes J45 "Asthma" and J46 "acute severe asthma" were included. Codes for associated co-morbidity at time of admission were identified, as well as month of admission and death, age, gender and length of stay. RESULTS: The mortality rate over the 5-year period was 1063 patients from 250,043 asthma admissions (0.43%). Critical care mortality was far higher and an annual rate indicated that for every 100,000 admissions 2878 (95% CI 2091;3857) patients died. Respiratory infection, cardiovascular disease and diabetes were common co-morbidities for all admissions. December and January had the peak number of deaths post asthma admission which were nearly all in adults, death being rarer in children. Women and those over 45 years had the highest rate of death which may reflect asthma prevalence. CONCLUSIONS: Co-morbid conditions experienced by older asthma patients may contribute to mortality post an asthma admission and greater understanding of risk factors contributing to fatality are required.

Consequences of delaying treatment intensification in type 2 diabetes: evidence from a UK database.

OBJECTIVE: Type 2 diabetes mellitus (TD2M) treatment focuses on achieving glycemic control, with HbA1c targeted at 6.5-7.5%. Clinicians commonly delay treatment intensification despite patients failing glycemic targets. This study evaluated longitudinal clinical and cost outcomes in patients failing metformin monotherapy using electronic medical records. RESEARCH DESIGN AND METHODS: Adults with incident T2DM were identified in the UK Clinical Practice Research Datalink (CPRD) from 1 January 2000 to 31 March 2014. Patients were initiated on metformin monotherapy but had not reached target (HbA1c <7%). Patients were grouped by time to intensification of second-line therapy from first recorded HbA1c ≥7%: Group A, rapid intensification within 365 days; Group B, delayed intensification days 366-1824; Group C, never intensified. Patients were followed from day 366 for 5 years until end of study, switch to insulin, migration or death. MAIN OUTCOME MEASURES: The study evaluated baseline clinical and medication characteristics which were re-evaluated each year, including HbA1c, weight, cholesterol and concomitant prescribing. RESULTS: A total of 6710 patients were included (Group A 2647, Group B 2452, Group C 1611). Group A achieved a significant decline in HbA1c at 1 year post-index date compared to Groups B and C (-1.13% Group A; +0.26% Group B, +0.16% Group C). A significantly higher proportion of patients achieved HbA1c target < 7% in Group A (Group A [45.8%]; Group B [19.1%], p < 0.0001). Using an adjusted hazard model, Group A was found to achieve the HbA1c target from the index date significantly faster than Group B (hazard ratio 3.25 [95% CI 2.87-3.69]). The most commonly prescribed second-line medications were sulfonylureas in Groups A and B throughout observation and were associated with significant weight gain (+1.3 kg per patient) in the adjusted models. CONCLUSIONS: Patients who were rapidly intensified achieved a maintained reduction in HbA1c faster than those with delayed intensification or no second-line therapy, despite a higher baseline HbA1c.

Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.

CONTEXT: Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions. OBJECTIVE: To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics). INTERVENTION: Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics). MAIN OUTCOME MEASURES: Symptom duration and severity. RESULTS: A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least "a slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02). CONCLUSION: No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.

Understanding the treatment of attention deficit hyperactivity disorder in newly diagnosed adult patients in general practice: a UK database study.

BACKGROUND: Adult attention deficit hyperactivity disorder (ADHD) has been largely ignored in psychiatric and general practice guidance until recently. Adult ADHD has a high social and medical burden, but health care is not well described in the UK. The main study objective was to evaluate a primary care adult ADHD population in terms of prescribing and health care contact rates. METHODS: This was a retrospective observational study using data from the Clinical Practice Research Database from January 1, 2002 to July 31, 2011. Adult patients with an incident ADHD diagnosis or ADHD medication were identified as having been free of ADHD medication or diagnoses in the previous 2 years. Patients were followed for 12-24 months after diagnosis. RESULTS: Of the 663 patients with ADHD in the cohort, 54.1% were prescribed ADHD medication during the observation period. During the first 6 months, 34.2% of patients initiated methylphenidates and 14.0% atomoxetine. In total, 36.3% patients were referred to secondary care psychiatry during observation, with the remaining population (63.7%) never having a referral. Most of the referrals were before diagnosis in primary care. At the end of the observation period, 16.2% of patients were on antipsychotics, 17.3% hypnotics, and 34.8% antidepressants or anxiolytics; however, some patients appeared to be prescribed antipsychotic or antidepressant medications even if they did not have an observable diagnosis in their records. Health care contact rates (general practitioner or hospital) increased by 39.2% post-diagnosis (incidence rate ratio: 1.39; 95% confidence interval: 1.32, 1.47), which may be related to the need for medication monitoring and titration. CONCLUSION: This study has shown in primary care that there is relatively low use of ADHD medication, low referrals into secondary care, high rates of usage of psychiatric non-ADHD medications for different indications, and an increasing burden in terms of health care contacts in adult ADHD patients post-diagnosis.

Gender differences in the management and experience of Chronic Obstructive Pulmonary Disease.

Whether women receive the same medical care for COPD as men and if they are at risk of different outcomes as a result, is not known. The Confronting COPD International Survey was performed in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK in 2000 with 3265 COPD participants. Forty-one per cent were women; mean age in women and men was 61.2 (SD 10.5) and 64.4 (11.0) years, mean pack-years of smoking 36 (29) and 46 (35) years, respectively. After adjusting for age, pack-years, country and severe dyspnea (MRC scores 5 and 4), women were less likely to have had spirometry (OR 0.84, 95% C.I. 0.72-0.98) but more likely to get smoking cessation advice (OR 1.57, 1.33-1.86). Despite significantly lower pack-years of smoking, women were more likely to report severe dyspnea than men (OR 1.30, 1.10-1.54), with similar cough (OR 1.08, 0.92-1.27) and less sputum (OR 0.84, 0.72-0.98). There were no differences in the risk of hospitalisation or emergency room visit. This study indicates that gender differences in COPD care and outcomes exist.