Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.</p> <p>Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda.</p> <p>Methods</p> <p>In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups.</p> <p>Results</p> <p>Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.</p> <p>Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).</p> <p>Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); <it>P</it>-value for homogeneity of risk differences = 0.006.</p> <p>Conclusion</p> <p>Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.</p> <p>The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy</p> <p>naïve HIV infected children in our environment.</p> <p>Clinical trials registration number</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00373100">NCT00373100</a></p

Measuring physiotherapy performance in patients with osteoarthritis of the knee: A prospective study

<p>Abstract</p> <p>Background</p> <p>Patients with knee osteoarthritis [OA] are commonly treated by physiotherapists in primary care. Measuring physiotherapy performance is important before developing strategies to improve quality. The purpose of this study was to measure physiotherapy performance in patients with knee OA by comparing clinical practice to evidence from systematic reviews.</p> <p>Methods</p> <p>We developed a data-collection form and invited all private practitioners in Norway [n = 2798] to prospectively collect data on the management of one patient with knee OA through 12 treatment session. Actual practice was compared to findings from an overview of systematic reviews summarising the effect of physiotherapy interventions for knee OA.</p> <p>Results</p> <p>A total of 297 physiotherapists reported their management for patients with knee OA. Exercise was the most common treatment used, provided by 98% of the physiotherapists. There is evidence of high quality that exercise reduces pain and improves function in patients with knee OA. Thirty-five percent of physiotherapists used acupuncture, low-level laser therapy or transcutaneous electrical nerve stimulation. There is evidence of moderate quality that these treatments reduce pain in knee OA. Patient education, supported by moderate quality evidence for improving psychological outcomes, was provided by 68%. Physiotherapists used a median of four different treatment modalities for each patient. They offered many treatment modalities based on evidence of low quality or without evidence from systematic reviews, e.g. traction and mobilisation, massage and stretching.</p> <p>Conclusion</p> <p>Exercise was used in almost all treatment sessions in the management of knee OA. This practice is desirable since it is supported by high quality evidence. Physiotherapists also provide several other treatment modalities based on evidence of moderate or low quality, or no evidence from systematic reviews. Ways to promote high quality evidence into physiotherapy practice should be identified and evaluated.</p

Patient Uncertainty Questionnaire-Rheumatology (PUQ-R): development and validation of a new patient-reported outcome instrument for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a mixed methods study

Background An in-depth qualitative exploration of uncertainty in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) led to the development of a five-domain conceptual framework of patient uncertainty in these two conditions. The purpose of this study was to develop and evaluate a new patient-reported outcome (PRO) instrument for patient uncertainty in SLE and RA on the basis of this empirically developed conceptual framework. Methods Cognitive debriefing interviews were conducted to pre-test the initial items generated on the basis of the preliminary qualitative exploration of patient uncertainty in SLE and RA. Two separate field tests were conducted in five hospital sites to evaluate the measurement properties of the new instrument; the first to identify and form scales, and the second to assess measurement properties of the final version in an independent sample. Psychometric evaluation was conducted in line with the Rasch Measurement Theory (RMT), examining the extent to which sample to scale targeting was satisfactory, measurement scales were constructed effectively and the sample was measured successfully. Traditional psychometric techniques were also used to provide complementary analyses best understood by clinicians. Results Pre-testing supported the relevance, acceptability and comprehensibility of the initial items. Findings indicated that the Patient Uncertainty Questionnaire for Rheumatology PUQ-R instrument fulfilled the expectations of RMT to a large extent (including person separation index 0.73 – 0.91). The PUQ-R comprises 49 items across five scales; symptoms and flares (14 items), medication (11 items), trust in doctor (8 items), self-management (6 items) and impact (10 items) which further displayed excellent measurement properties as assessed against the traditional psychometric criteria (including Cronbach’s alpha 0.82 – 0.93). Conclusion The PUQ-R has been developed and evaluated specifically for patients with SLE and RA. By quantifying uncertainty, the PUQ-R has the potential to support evidence-based management programmes and research

Ethological principles predict the neuropeptides co-opted to influence parenting

Ethologists predicted that parental care evolves by modifying behavioural precursors in the asocial ancestor. As a corollary, we predict that the evolved mechanistic changes reside in genetic pathways underlying these traits. Here we test our hypothesis in female burying beetles, Nicrophorus vespilloides, an insect where caring adults regurgitate food to begging, dependent offspring. We quantify neuropeptide abundance in brains collected from three behavioural states: solitary virgins, individuals actively parenting or post-parenting solitary adults and quantify 133 peptides belonging to 18 neuropeptides. Eight neuropeptides differ in abundance in one or more states, with increased abundance during parenting in seven. None of these eight neuropeptides have been associated with parental care previously, but all have roles in predicted behavioural precursors for parenting. Our study supports the hypothesis that predictable traits and pathways are targets of selection during the evolution of parenting and suggests additional candidate neuropeptides to study in the context of parenting

MHC-IIB Filament Assembly and Cellular Localization Are Governed by the Rod Net Charge

Actin-dependent myosin II molecular motors form an integral part of the cell cytoskeleton. Myosin II molecules contain a long coiled-coil rod that mediates filament assembly required for myosin II to exert its full activity. The exact mechanisms orchestrating filament assembly are not fully understood., negatively-charged regions of the coiled-coil were found to play an important role by controlling the intracellular localization of native MHC-IIB. The entire positively-charged region is also important for intracellular localization of native MHC-IIB.A correct distribution of positive and negative charges along myosin II rod is a necessary component in proper filament assembly and intracellular localization of MHC-IIB

Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

This is the final version. Available from the publisher via the DOI in this record.UK Biobank Sleep Traits GWAS summary statistics are available at the Sleep Disorder Knowledge Portal (SDKP) website (http://www.sleepdisordergenetics.org). All other data are contained within the article and its supplementary information or available upon request.Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.Medical Research Council (MRC

Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations.</p> <p>Methods</p> <p>A literature search was conducted using the <it>Medline</it>, <it>Embase </it>and <it>International Pharmaceutical Abstracts </it>databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems.</p> <p>Results</p> <p>Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies.</p> <p>Conclusions</p> <p>Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.</p

Change in basic motor abilities, quality of movement and everyday activities following intensive, goal-directed, activity-focused physiotherapy in a group setting for children with cerebral palsy

Background: The effects of intensive training for children with cerebral palsy (CP) remain uncertain. The aim of the study was to investigate the impact on motor function, quality of movements and everyday activities of three hours of goal-directed activity-focused physiotherapy in a group setting, five days a week for a period of three weeks. Methods: A repeated measures design was applied with three baseline and two follow up assessments; immediately and three weeks after intervention. Twenty-two children with hemiplegia (n = 7), diplegia (n = 11), quadriplegia (n = 2) and ataxia (n = 2) participated, age ranging 3-9 y. All levels of Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) were represented. Parents and professionals participated in goal setting and training. ANOVA was used to analyse change over repeated measures. Results: A main effect of time was shown in the primary outcome measure; Gross Motor Function Measure-66 (GMFM- 66), mean change being 4.5 (p < 0.01) from last baseline to last follow up assessment. An interaction between time and GMFCS-levels was found, implying that children classified to GMFCS-levels I-II improved more than children classified to levels III-V. There were no main or interaction effects of age or anti-spastic medication. Change scores in the Pediatric Evaluation of Disability Inventory (PEDI) ranged 2.0-6.7, p < 0.01 in the Self-care domain of the Functional Skills dimension, and the Self-care and Mobility domains of the Caregiver Assistance dimension. The children's individual goals were on average attained, Mean Goal Attainment Scaling (GAS) T-score being 51.3. Non-significant improved scores on the Gross Motor Performance Measure (GMPM) and the Quality of Upper Extremities Skills Test (QUEST) were demonstrated. Significant improvement in GMPM scores were found in improved items of the GMFM, not in items that maintained the same score. Conclusions: Basic motor abilities and self-care improved in young children with CP after goal-directed activityfocused physiotherapy with involvement of their local environment, and their need for caregiver assistance in self-care and mobility decreased. The individualized training within a group context during a limited period of time was feasible and well-tolerated. The coherence between acquisition of basic motor abilities and quality of movement should be further examined

Antibiotics prescribing practices in oral implantology among jordanian dentists. A cross sectional, observational study

<p>Abstract</p> <p>Background</p> <p>In oral implantology, there is no consensus on the most appropriate regimen for antibiotics prescribing, the decision to prescribe antibiotic is usually based on procedure, patient and clinician related factors. The aim of this study was to investigate the rationale of antibiotic prescribing among Jordanian clinicians who practice oral implantology.</p> <p>Findings</p> <p>The target sample for the study was the 250 Jordan Dental Implant Group members. A five page questionnaire contained 41 questions, both closed and open questions were used to collect data. Statistical analysis was performed using SPSS Windows 16.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were generated.</p> <p>The response rate was (70.4%) 176/250. Mean age was 37.2 yrs, 49.4% always prescribe antibiotics mainly oral amoxicillin and amoxicillin with clavulinic acid. Antibiotics prescribing increased with flap raising, multiple implants and sinus or bone augmentation. Patient medical condition, periodontitis and oral hygiene were the most important clinical factors in antibiotic prescribing, non-clinical factors were; reading scientific materials, courses and lectures, knowledge gained during training, and the effectiveness and previous experience with the drug.</p> <p>Conclusions</p> <p>Wide variations in antibiotics types, routes, dose and duration of administration were found. Recommendations on antibiotic prescribing are needed to prevent antibiotic overprescribing and misuse.</p