Patients’ knowledge on prescribed medications play a key role in the long term management of cardiac diseases and in determining their outcome. The present study evaluates the knowledge about prescribed medication among cardiac patients and aim to identify factors influencing knowledge.
A descriptive-cross-sectional study was conducted among 200 adult patients attending clinics at the Cardiology Unit of the National Hospital of Sri Lanka. Knowledge assessment focused on four different sections; drug name, dose, frequency and indication. The total score of 60 was calculated by giving each component the following weighted scores; drug name = 20, indication = 20, drug dose = 10 and frequency = 10. A binary logistic regression analysis to evaluate factors associated with ‘good knowledge’ (total score ≥ 40) was performed.
Among 200 participants 56.5% (n = 113) were males. Mean age was 59.7 ± 8.2 years and a majority (n = 170, 85.0%) were older than 50 years of age. Sinhala was the primary language of 91.5% (n = 183) of participants, while English was the primary language in only two of the study participants (1.0%). Eighty four percent of the participants were educated up to secondary education or above, while 2.5% (n = 5) had no formal education. The overall knowledge (total score-60) on prescribed medications among the study population was ‘poor’ (score ≤ 20) in 46%, ‘adequate’ (score 21–40) in 36.5% and ‘good’ (score ≥ 40) in 17.5%. The results of the binary logistic regression analysis indicates that Secondary (OR-1.53) and Tertiary levels (OR-2.79) of education, self-reported perception of illness as being Moderate (OR-1.23) or Severe (OR-1.70) and being educated by a doctor (as reported by patients) (OR-1.69) significantly increased the odds of having a ‘Good Knowledge of Drugs’. Majority of the patients were unable to read and understand the information written in English. The doctor’s contributed towards educating on drug information only in 33.0% of the patients.
In a resource-poor setting in patients with Limited English Proficiency, lower level of education and misperception of illness severity resulted in reduced knowledge on prescribed medications. Furthermore, being educated by a doctor significantly improved knowledge. However the doctors’ contribution at present to deliver quality health information to their patients was at an unsatisfactory level.
Limited English proficiency; Health literacy; Sri Lanka; Cardiac disease
Interleukin-15 (IL-15) is a pleiotropic cytokine with a broad range of biological functions in many diverse cell types. It plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. This review provides an overview of the mechanisms by which IL-15 modulates the host response to infectious agents and its utility as a cytokine adjuvant in vaccines against infectious pathogens.
IL-15; infectious diseases; vaccines; inflammation; molecular adjuvants
To study influenza viruses in pigs in Sri Lanka,we examined samples from pigs at slaughterhouses. Influenza (H3N2) and A(H1N1)pdm09 viruses were prevalent during 2004–2005 and 2009–2012, respectively. Genetic and epidemiologic analyses of human and swine influenza viruses indicated 2 events of A(H1N1)pdm09 virus spillover from humans to pigs.
swine influenza; Sri Lanka; epidemiology; viruses; spillover; ecology; A(H1N1)pdm09; influenza
Botanical work since 2008 on the Sleeping Giant section of the Kamdebooberge (Sneeuberg mountain complex, Eastern Cape, South Africa) has indicated that these mountains may be of significant conservation value. Accordingly, a precursory, rapid multi-disciplinary biodiversity assessment was undertaken in January 2011, focusing on plants, tetrapod vertebrates and leafhoppers. The botanical results confirm the Kamdebooberge as being of high botanical conservation value, hosting three strict endemics, healthy populations of five other Sneeuberg endemics, and fynbos communities comprising species not found elsewhere in the Sneeuberg. The Kamdebooberge are important for herpetofauna (excluding serpentoids) and mammals, hosting several range-restricted and regional endemics. The expedition uncovered three new leafhopper species, together with several species previously only known from the Cape Floristic Region. Further detailed faunal work may provide further interesting results from these mountains, which show a high conservation value unique to the southern Escarpment.
Electronic supplementary material
The online version of this article (doi:10.1186/2193-1801-1-56) contains supplementary material, which is available to authorized users.
Endemics; Great escarpment; Kamdebooberge; Plants; Invertebrates; Sneeuberg centre of floristic endemism; Vertebrates
To evaluate short- and long-term effects of Cinnamomum zeylanicum on food consumption, body weight, glycemic control, and lipids in healthy and diabetes-induced rats.
Materials and Methods:
The study was conducted in two phases (Phase I and Phase II), using Sprague-Dawley rats in four groups. Phase I evaluated acute effects on fasting blood glucose (FBG) (Groups 1 and 2) and on post-oral glucose (Groups 3 and 4) blood glucose. Groups 1 and 3 received distilled-water and Groups 2 and 4 received cinnamon-extracts. Phase II evaluated effects on food consumption, body weight, blood glucose, and lipids over 1 month. Group A (n = 8, distilled-water) and Group B (n = 8, cinnamon-extracts) were healthy rats, while Group C (n = 5, distilled-water) and Group D (n = 5, cinnamon-extracts) were diabetes-induced rats. Serum lipid profile and HbA1c were measured on D-0 and D-30. FBG, 2-h post-prandial blood glucose, body weight, and food consumption were measured on every fifth day.
Phase I: There was no significant difference in serial blood glucose values in cinnamon-treated group from time 0 (P > 0.05). Following oral glucose, the cinnamon group demonstrated a faster decline in blood glucose compared to controls (P < 0.05). Phase II: Between D0 and D30, the difference in food consumption was shown only in diabetes-induced rats (P < 0.001). Similarly, the significant difference following cinnamon-extracts in FBG and 2-h post-prandial blood glucose from D0 to D30 was shown only in diabetes-induced rats. In cinnamon-extracts administered groups, total and LDL cholesterol levels were lower on D30 in both healthy and diabetes-induced animals (P < 0.001).
C. zeylanicum lowered blood glucose, reduced food intake, and improved lipid parameters in diabetes-induced rats.
Blood glucose; Ceylon cinnamon; Cinnamomum zeylanicum; diabetes mellitus; lipids; Sprague-Dawley rats
Despite the eradication of smallpox, there is heightened concern that it could be reintroduced as a result of intentional release of Variola major virus through an act of bioterrorism. The live vaccine that was pivotal in the eradication of smallpox though considered a gold standard for its efficacy still retains sufficient residual virulence that can cause life-threatening sequelae especially in immune deficient individuals. Therefore, a safer smallpox vaccine that can match the efficacy of first generation vaccines is urgently needed. We previously reported that the integration of human IL-15 cytokine into the genome of Wyeth strain of vaccinia (Wyeth/IL-15), the same strain as the licensed vaccine, generates a vaccine with superior immunogenicity and efficacy in a mouse model. We now demonstrate that Wyeth/IL-15 is non-lethal to athymic nude mice when administered intravenously at a dose of 107 plaque forming units and it undergoes enhanced in vivo clearance in these immune deficient mice. Furthermore, a majority of cynomolgus monkeys vaccinated with vaccinia viruses with integrated IL-15, when challenged 3 years later with a lethal dose of monkeypox virus displayed milder clinical manifestations with complete recovery supporting the utility of Wyeth/IL-15 for contemporary populations as a safer and efficacious smallpox vaccine.
Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted dosage design is therefore feasible.
Brain targeted; electroencephalography; emissary veins; diazepam; sesame oil; sleep latency; transcranial
Tuberculosis caused by Mycobacterium tuberculosis is responsible for nearly two million deaths every year globally. A single licensed vaccine derived from Mycobacterium bovis, bacille Calmette-Guerin (BCG) administered perinatally as a prophylactic vaccine has been in use for over 80 years and confers substantial protection against childhood tuberculous meningitis and miliary tuberculosis. However, the BCG vaccine is virtually ineffective against the adult pulmonary form of tuberculosis that is pivotal in the transmission of tuberculosis that has infected almost 33% of the global population. Thus, an effective vaccine to both prevent tuberculosis and reduce its transmission is urgently needed. We have generated a multi-valent, vectored vaccine candidate utilizing the modified virus Ankara (MVA) strain of vaccinia virus to tandemly express five antigens, ESAT6, Ag85A, Ag85B, HSP65 and Mtb39A of Mycobacterium tuberculosis that have been reported to be protective individually in certain animal models together with an immunostimulatory cytokine interleukin 15 (MVA/IL-15/5Mtb). Although, immunological correlates of protection against tuberculosis in humans remain to be established, we demonstrate that our vaccine induced comparable CD4+ T cell and greater CD8+ T cell and antibody responses against Mycobacterium tuberculosis in vaccinated mice in a direct comparison with the BCG vaccine and conferred protection against an aerogenic challenge of M. tuberculosis, thus warranting its further preclinical development.
Tuberculosis; vaccine; IL-15
The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune-stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein, derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing antibodies and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with H5N1 virus of a different clade. In addition to having the potential as a universal influenza vaccine, in the event of an impending pandemic, the Wyeth/IL-15/5Flu is also readily amenable for bulk production to cover the global population. For those individuals for whom the use of Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
Viral; Cytokines; vaccination
Most medical schools use simulated patients (SPs) for teaching. In this context the authenticity of role play and quality of feedback provided by SPs is of paramount importance. The available literature on SP training mostly addresses instructor led training where the SPs are given direction on their roles. This study focuses on the use of peer and self evaluation as a tool to train SPs.
SPs at the medical school participated in a staff development and training programme which included a) self-assessment of their performance while observing video-tapes of their role play using a structured guide and b) peer group assessment of their performance under tutor guidance. The pre and post training performance in relation to authenticity of role play and quality of feedback was blindly assessed by students and tutors using a validated instrument and the scores were compared. A focus group discussion and a questionnaire assessed acceptability of the training programme by the SPs.
The post-training performance assessment scores were significantly higher (p < 0.05) than the pre-training scores. The degree of improvement in the quality of feedback provided to students was more when compared to the improvement of role play. The acceptability of the training by the SPs was very satisfactory scoring an average of 7.6 out of 10. The majority of the SPs requested the new method of training to be included in their current training programme as a regular feature.
Use of structured self-reflective and peer-interactive, practice based methods of SP training is recommended to improve SP performance. More studies on these methods of training may further refine SP training and lead to improvement of SP performance which in turn may positively impact medical education.
The prevalence of macrovascular disease and hyperlipidaemia was examined in 500 patients with non-insulin-dependent diabetes mellitus attending a diabetic clinic in a Sri Lankan teaching hospital and 250 controls matched for age and gender. Macrovascular disease was assessed using a modified World Health Organisation questionnaire and modified Minnesota coding of electrocardiogram recordings. Twenty-one per cent of diabetic patients and 14.3% of controls had hypercholesterolaemia (P < 0.05). Macrovascular disease was present in 13.4% of diabetic patients and 8.2% of controls. Significant differences were seen in the prevalence of hypertension (15.6% vs 4.8%, P < 0.05), obesity (16.2% vs 9.7%, P < 0.05), peripheral vascular disease (5.6% vs 2%, P < 0.05) and electrocardiographic abnormalities (12% vs 6%, P < 0.05) in diabetic patients when compared to controls. Hyperlipidaemia and macrovascular disease is common in non-insulin-dependent diabetic patients in Sri Lanka and accounts for significant morbidity.
Medication use is a potentially reversible cause of urinary incontinence (UI). The objective of this longitudinal cohort study was to evaluate whether self-reported UI in community-dwelling older women is associated with the use of different classes of antihypertensive agents.
The sample consisted of 959 black and white women aged 72–81 years without baseline (Year 1) UI from the Health, Aging, and Body Composition Study. Use of any antihypertensive from 10 drug classes (ie, alpha blockers [central], alpha blockers [peripheral], angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta blockers, calcium channel blockers, diuretics [loop], diuretics [potassium-sparing], diuretics [thiazide], and vasodilators) was determined during Year 3 in-person interviews. The number of unique antihypertensive agents used and the standardized daily dosage were also examined. Self-reported UI, operationally defined as leaking urine at least weekly during the previous 12 months, was assessed at Year 4 visits.
A total of 197 women (20.5%) reported UI at Year 4. Although any antihypertensive use, number of agents used, and standardized daily dosage at Year 3 were not associated with UI at Year 4, use of one particular drug class—peripheral alpha blockers (ie, doxazosin, prazosin, and terazosin)—was associated with fourfold greater odds of UI (adjusted odds ratio = 4.47; 95% confidence interval = 1.79–11.21; p = .0014). Further, in post hoc analyses, these odds nearly doubled in those also taking loop diuretics (adjusted odds ratio = 8.81; 95% confidence interval = 1.78–43.53; p = .0076).
In community-dwelling older women, peripheral alpha blocker use was associated with UI, and the odds nearly doubled when used with loop diuretics.
Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin-/-) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser.
Wild type (WT) and hevin-/- mice were divided into three groups at 4 time points- 1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin-/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice.
Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin-/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing.
Protein kinases are key components of most mammalian signal transduction networks and are therapeutically relevant drug targets. Efforts to study protein kinase function would benefit from new technologies that are able to profile kinases in complex proteomes. Here, we describe active site-directed probes for profiling kinases in whole cell extracts and live cells. These probes contain general ligands that stabilize a specific inactive conformation of the ATP-binding sites of protein kinases, as well as trifluoromethylphenyl diazirine and alkyne moieties that allow covalent modification and enrichment of kinases, respectively. A diverse group of serine/threonine and tyrosine kinases were identified as specific targets of these probes in whole cell extracts. In addition, a number of kinase targets were selectively labeled in live cells. Our chemical proteomics approach should be valuable for interrogating protein kinase active sites in physiologically relevant environments.
This study employs social ecology to evaluate psychosocial wellbeing in a cross-sectional sample of 142 former child soldiers in Nepal. Outcome measures included the Depression Self Rating Scale (DSRS), Child Posttraumatic Stress Scale (CPSS), and locally developed measures of function impairment and reintegration. At the child level, traumatic exposures, especially torture, predicted poor outcomes, while education improved outcomes. At the family level, conflict-related death of a relative, physical abuse in the household, and loss of wealth during the conflict predicted poor outcomes. At the community level, living in high caste Hindu communities predicted fewer reintegration supports. Ultimately, social ecology is well-suited to identify intervention foci across ecological levels, based on community differences in vulnerability and protective factors.
Child soldiers; posttraumatic stress disorder (PTSD); war; social ecology; Nepal
To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults.
A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT).
The overall prevalence (95% C.I.) of anaemia (Hb <13.5g/dl men and 11.3 g/dl women) was 4.6% (2.9%–6.4%) in men and 1.0% (0.2%–1.9%) in women. Iron deficiency (ferritin <17ng/ml men and <11ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3ng/ml) and serum B12 (<120ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%).
Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.
Previously we reported that airborne concentrations of cis-permethrin, but not trans-permethrin, measured during pregnancy in an inner city pediatric cohort was associated with cough by age 5. However, the effect of subsequent exposures to both permethrins during early childhood, and to piperonyl butoxide (PBO, a synergist for residential pyrethroid insecticides) remains to be elucidated. We hypothesized that prenatal and age 5-6 year measures of PBO and permethrins would be associated with cough at age 5-6 years in this cohort. Further, we explored the associations between these pesticides measures and wheeze, asthma, seroatopy, and fractional exhaled nitric oxide (FeNO).
PBO and permethrins were measured in personal air during the third trimester of pregnancy and indoor residential air at age 5-6 years (n=224). Health outcome questionnaires were administered to the mothers of 5-6 years old children. Indoor allergen specific and total immunoglobulin (Ig) E production was measured from sera collected at age 5, and FeNO was measured at 5-6 years. The hypotheses were tested using regression models adjusting for common confounders.
Noninfectious cough was reported among 14% of children at age 5-6 years. Measures of prenatal PBO, but not age 5-6 year PBO or permethrins, increased the odds of cough [OR (95% CI): 1.27 (1.09-1.48), p<0.01; n=217]. No significant associations were found for other measured health outcomes.
Prenatal PBO exposure was associated with childhood cough. It is unclear whether the observed effect is due mainly to PBO itself or residential pyrethroids of which PBO is an indicator.
prenatal pesticide exposure; cough; piperonyl butoxide; permethrin
The activation of heterodimeric (α/β) integrin transmembrane receptors by
cytosolic protein talin is crucial for regulating diverse cell-adhesion-dependent
processes, including blood coagulation, tissue remodeling, and cancer metastasis. This
process is triggered by the coincident binding of N-terminal FERM
(four-point-one-protein/ezrin/radixin/moesin) domain of talin (talin-FERM) to the inner
membrane surface and integrin β cytoplasmic tail, but how these binding events are
spatiotemporally regulated remains obscure. Here we report the crystal structure of a
dormant talin, revealing how a C-terminal talin rod segment (talin-RS) self-masks a key
integrin-binding site on talin-FERM via a large interface. Unexpectedly, the structure
also reveals a distinct negatively charged surface on talin-RS that electrostatically
hinders the talin-FERM binding to the membrane. Such a dual inhibitory topology for talin
is consistent with the biochemical and functional data, but differs significantly from a
previous model. We show that upon enrichment with phosphotidylinositol-4,5-bisphosphate
(PIP2) – a known talin activator, membrane strongly attracts a positively charged
surface on talin-FERM and simultaneously repels the negatively charged surface on
talin-RS. Such an electrostatic “pull-push” process promotes the relief of the
dual inhibition of talin-FERM, which differs from the classic “steric clash”
model for conventional PIP2-induced FERM domain activation. These data therefore unravel a
new type of membrane-dependent FERM domain regulation and illustrate how it mediates the
talin on/off switches to regulate integrin transmembrane signaling and cell adhesion.
cell adhesion; FERM domain; integrin signaling; crystallography; NMR
Rationale: Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children’s phthalate exposures and fractional exhaled nitric oxide (FeNO), a biomarker of airway inflammation, have not been examined.
Objectives: We hypothesized that urinary concentrations of four phthalate metabolites would be positively associated with FeNO and that these associations would be stronger among children with seroatopy or wheeze.
Methods: In an urban ongoing birth cohort, 244 children had phthalate metabolites determined in urine collected on the same day as FeNO measurement. Repeated sampling gathered 313 observations between ages 4.9 and 9.1 years. Seroatopy was assessed by specific IgE. Wheeze in the past year was assessed by validated questionnaire. Regression models used generalized estimating equations.
Measurements and Main Results: Log-unit increases in urinary concentrations of metabolites of diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) were associated with a 6.6% (95% confidence interval [CI] 0.5–13.1%) and 8.7% (95% CI, 1.9–16.0%) increase in FeNO, respectively, adjusting for other phthalate metabolites and potential covariates/confounders. There was no association between concentrations of metabolites of di(2-ethylhexyl) phthalate or di-n-butyl phthalate and FeNO. There was no significant interaction by seroatopy. The BBzP metabolite association was significantly stronger among children who wheeze (P = 0.016).
Conclusions: Independent associations between exposures to DEP and BBzP and FeNO in a cohort of inner-city children were observed. These results suggest that these two ubiquitous phthalates, previously shown to have substantial contributions from inhalation, are positively associated with airway inflammation in children.
airway inflammation; asthma; diethyl phthalate; butylbenzyl phthalate; fractional exhaled nitric oxide
Introduction and Rationale
National influenza immunization rates for healthcare workers (HCW) in long-term care (LTC) remain unacceptably low. This poses a serious public health threat to residents. Prior work has suggested high staff turnover rates as a contributing factor to low immunization rates. There is a critical need to identify and deploy successful models of HCW influenza immunization programs to LTC facilities. This report describes one potential model that has been successfully initiated in a network of LTC facilities.
All facilities served by a single regional LTC pharmacy were invited to participate in a HCW influenza immunization program. This voluntary immunization program began in 2005 and continues to the present. As part of the program, the pharmacy promoted organizational change by assuming oversight and control of HCW immunization policies and processes for all facilities. Primary and secondary outcomes are the number of facilities reaching HCW influenza immunization rates of 60% and 80%.
Fourteen of the sixteen LTC facilities participated. Facilities were diverse and included both nursing and assisted living facilities; unionized and nonunionized facilities; and urban, suburban and rural facilities. The pharmacy provided educational and communication materials, centralized data collection using a standardized definition for HCW immunization rates, and facility feedback. All fourteen LTC facilities achieved the primary goal of 60% and nearly two thirds reached the secondary goal of 80%. Twenty percent reached the new Healthy People 2020 goal of 90%.
It is possible for LTC facilities to improve HCW immunization rates using a pharmacy based, voluntary HCW influenza immunization approach. Such an approach may help attenuate the negative influence of staff turnover on HCW immunizations. Attainment of the new Health People 2020 goals still remains a challenge and may require mandatory programs.
healthcare workers; healthcare worker immunization; immunization programs; long-term care; nursing homes; immunizations; influenza
We identified human bocavirus (HBoV) DNA by PCR in cerebrospinal fluid from adults and children with encephalitis in Sri Lanka. HBoV types 1, 2, and 3 were identified among these cases. Phylogenetic analysis of HBoV1 strain sequences found no subclustering with strains previously identified among encephalitis cases in Bangladesh.
encephalitis; bocavirus; molecular epidemiology; Sri Lanka; viruses; zoonoses
Neuropathic pain is a chronic symptom of multiple sclerosis (MS) and affects nearly half of all MS sufferers. A key instigator of this pain is the pro-inflammatory response in MS. We investigated the behavioral effects of immunization with a mutant peptide of myelin basic protein (MBP), termed altered peptide ligand (APL), known to initiate immune deviation from a pro-inflammatory state to an anti-inflammatory response in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male and female Lewis rats were injected with vehicle control or with varying doses of 50 or 100 μg guinea pig MBP in combination with or without APL. APL-treated animals established significantly lower disease severity compared to encephalitogenic MBP-treated animals. Animals with EAE developed mechanical, but not thermal pain hypersensitivity. Mechanical pain sensitivities were either improved or normalized during periods of clinical disease in male and female APL-treated animals as compared to the encephalitogenic group. No significant changes to thermal latency were observed upon co-immunization with APL. Together these data indicate that APL ameliorates disease states and selectively mediates an analgesic effect on EAE animals.
experimental autoimmune encephalomyelitis; altered peptide ligand; multiple sclerosis; mechanical allodynia; thermal hyperalgesia; nociception
Background. The effects of coconut fat and soya fat on serum lipids are controversial. This study was designed to investigate the lipid effects of coconut milk and soya milk supplementation on the lipid profile of free living healthy subjects. Methods. Sixty (60) healthy volunteers aged 18–57 years were given coconut milk porridge (CMP) for 5 days of the week for 8 weeks, followed by a 2-week washout period, subsequent to which they received isoenergetic soya milk porridge (SMP) for 8 weeks. Results. The LDL (low density lipoprotein) levels decreased with CMP and reached statistical significance in the total study population and in the >130 baseline LDL group. The HDL (high density lipoprotein) levels rose significantly with CMP supplementation (P = 0.000). Conclusions. We conclude that coconut fat in the form of CM does not cause a detrimental effect on the lipid profile in the general population and in fact is beneficial due to the decrease in LDL and rise in HDL. SMP will be of benefit only in those whose baseline LDL levels are elevated.
Older blacks are less likely to receive guideline-recommended antilipemic therapy and achieve lipid control than older whites due in part to out-of-pocket costs. We sought to determine whether racial differences in antilipemic use and lipid control narrowed after Medicare Part D’s implementation.
This before-after study included 1091 black and white adults age >70 with coronary heart disease and/or diabetes mellitus from the Health Aging and Body Composition Study. Primary outcomes were antilipemic use and LDL-C control. Key independent variables were race, time (pre- vs. post-Part D), and their interaction.
Before Part D, fewer blacks than whites reported taking an antilipemic (32.70% vs 49.35%) and this difference was sustained after Part D (blacks 48.30% vs whites 64.57%). Multivariable generalized estimating equations confirmed no post Part D change in racial differences in antilipemic use (adjusted ratio of the odds ratios [AROR] 1.07, 95% CI 0.79–1.45). Compared to whites, more blacks had poor lipid control both before Part D (24.30% vs 12.36% respectively) and after Part D (24.46% vs 13.72% respectively), with no post Part D change in racial differences in lipid control (AROR 0.82, 95% CI 0.51–1.33).
While antilipemic use increased after Medicare Part D for both races, this policy change was associated neither with a change in lipid control for either racial group nor in the racial differences in antilipemic use or lipid control.
The proportion of proposed new treatments that are ’successful’ is of ethical, scientific, and public importance. We investigated how often new, experimental treatments evaluated in randomized controlled trials (RCTs) are superior to established treatments.
Our main question was: “On average how often are new treatments more effective, equally effective or less effective than established treatments?” Additionally, we wanted to explain the observed results, i.e. whether the observed distribution of outcomes is consistent with the ’uncertainty requirement’ for enrollment in RCTs. We also investigated the effect of choice of comparator (active versus no treatment/placebo) on the observed results.
We searched the Cochrane Methodology Register (CMR) 2010, Issue 1 in The Cochrane Library (searched 31 March 2010); MEDLINE Ovid 1950 to March Week 2 2010 (searched 24 March 2010); and EMBASE Ovid 1980 to 2010 Week 11 (searched 24 March 2010).
Cohorts of studies were eligible for the analysis if they met all of the following criteria: (i) consecutive series of RCTs, (ii) registered at or before study onset, and (iii) compared new against established treatments in humans.
Data collection and analysis
RCTs from four cohorts of RCTs met all inclusion criteria and provided data from 743 RCTs involving 297,744 patients. All four cohorts consisted of publicly funded trials. Two cohorts involved evaluations of new treatments in cancer, one in neurological disorders, and one for mixed types of diseases. We employed kernel density estimation, meta-analysis and meta-regression to assess the probability of new treatments being superior to established treatments in their effect on primary outcomes and overall survival.
The distribution of effects seen was generally symmetrical in the size of difference between new versus established treatments. Meta-analytic pooling indicated that, on average, new treatments were slightly more favorable both in terms of their effect on reducing the primary outcomes (hazard ratio (HR)/odds ratio (OR) 0.91, 99% confidence interval (CI) 0.88 to 0.95) and improving overall survival (HR 0.95, 99% CI 0.92 to 0.98). No heterogeneity was observed in the analysis based on primary outcomes or overall survival (I2 = 0%). Kernel density analysis was consistent with the meta-analysis, but showed a fairly symmetrical distribution of new versus established treatments indicating unpredictability in the results. This was consistent with the interpretation that new treatments are only slightly superior to established treatments when tested in RCTs. Additionally, meta-regression demonstrated that results have remained stable over time and that the success rate of new treatments has not changed over the last half century of clinical trials. The results were not significantly affected by the choice of comparator (active versus placebo/no therapy).
Society can expect that slightly more than half of new experimental treatments will prove to be better than established treatments when tested in RCTs, but few will be substantially better. This is an important finding for patients (as they contemplate participation in RCTs), researchers (as they plan design of the new trials), and funders (as they assess the ’return on investment’). Although we provide the current best evidence on the question of expected ’success rate’ of new versus established treatments consistent with a priori theoretical predictions reflective of ’uncertainty or equipoise hypothesis’, it should be noted that our sample represents less than 1% of all available randomized trials; therefore, one should exercise the appropriate caution in interpretation of our findings. In addition, our conclusion applies to publicly funded trials only, as we did not include studies funded by commercial sponsors in our analysis.