Treatment choices for fevers in children under-five years in a rural Ghanaian district

<p>Abstract</p> <p>Background</p> <p>Health care demand studies help to examine the behaviour of individuals and households during illnesses. Few of existing health care demand studies examine the choice of treatment services for childhood illnesses. Besides, in their analyses, many of the existing studies compare alternative treatment options to a single option, usually self-medication. This study aims at examining the factors that influence the choices that caregivers of children under-five years make regarding treatment of fevers due to malaria and pneumonia in a rural setting. The study also examines how the choice of alternative treatment options compare with each other.</p> <p>Methods</p> <p>The study uses data from a 2006 household socio-economic survey and health and demographic surveillance covering caregivers of 529 children under-five years of age in the Dangme West District and applies a multinomial probit technique to model the choice of treatment services for fevers in under-fives in rural Ghana. Four health care options are considered: self-medication, over-the-counter providers, public providers and private providers.</p> <p>Results</p> <p>The findings indicate that longer travel, waiting and treatment times encourage people to use self-medication and over-the-counter providers compared to public and private providers. Caregivers with health insurance coverage also use care from public providers compared to over-the-counter or private providers. Caregivers with higher incomes use public and private providers over self-medication while higher treatment charges and longer times at public facilities encourage caregivers to resort to private providers. Besides, caregivers of female under-fives use self-care while caregivers of male under-fives use public providers instead of self-care, implying gender disparity in the choice of treatment.</p> <p>Conclusions</p> <p>The results of this study imply that efforts at curbing under-five mortality due to malaria and pneumonia need to take into account care-seeking behaviour of caregivers of under-fives as well as implementation of strategies.</p

Improved mapping strategy to better inform policy on the control of schistosomiasis and soil-transmitted helminthiasis in Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis and soil-transmitted helminthiasis (STH) are endemic in Sierra Leone confirmed by national mapping in 2008. To better inform planning of preventive chemotherapy strategy, another survey was conducted before mass drug administration (MDA) in seven districts according to the mapping results or local knowledge. Fifty-nine chiefdoms and one school in every chiefdom were selected. Thirty school children aged 9-14 years from each school (total: 1760) were examined by parasitological methods for infection with <it>Schistosoma mansoni </it>and STHs.</p> <p>Results</p> <p>The overall prevalence of <it>S. mansoni </it>was 40.2% (95% confidence interval (CI): 37.9-42.5%), particularly in Kailahun (63.3%), Kenema (46.7%), Koinadugu (41.9%) and Kono (71.7%). The results demonstrated the focal distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts with prevalence ranging from 0.0-63.3%, 3.3-90.0% and 0.0-67.9% respectively. The arithmetic mean intensity of <it>S. mansoni </it>infection was 95.4 epg (95% CI: 61.4-129.5 epg), Heavy mean intensity of infection was found in Kailahun (120.2 epg), Kenema (104.5 epg), Koinadugu (112.3 epg) and Kono (250.3 epg). Heavy or moderate infection with <it>S. mansoni </it>occurred in 20.7% of children examined. Hookworm prevalence was moderate: 31.2% (95% CI: 29.1-33.4%), but high in Bo (50.0%) and Tonkolili (56.7%). Hookworm intensity of infection was light with a mean epg of 53.0 (95% CI: 38.4-67.7 epg). Prevalence and intensity of <it>Ascaris lumbricoides </it>(1.5%, 17.8 epg) and <it>Trichuris trichiura </it>(2.5%, 20.3 epg) was low.</p> <p>Conclusions</p> <p>The prediction by previous spatial analysis that <it>S. mansoni </it>was highly endemic across north-eastern Sierra Leone was confirmed with a significant proportion of children heavily or moderately infected. The distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts ranged widely, highlighting the importance of considering the nature of focal transmission in national mapping exercises. These results were used to refine the MDA for schistosomiasis control to chiefdom implementation units rather than the entire district in these 3 districts. The survey demonstrated that sufficient number of survey sites for schistosomiasis mapping in each district should be used to provide a better national planning of MDA activities, and that it is affordable with the contributions from all parties involved and national resources mobilized.</p

Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor

Contains fulltext : 69595.pdf (publisher's version ) (Closed access)PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy

Character pathology and neuropsychological test performance in remitted opiate dependence

<p>Abstract</p> <p>Background</p> <p>Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies.</p> <p>Methods</p> <p>The Millon Multiaxial Clinical Inventory (MCMI) and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM), 27 subjects in protracted abstinence from methadone maintenance treatment (PA), and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis.</p> <p>Results</p> <p>MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use.</p> <p>Conclusion</p> <p>Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects.</p

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. RESULTS: A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. CONCLUSION: Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved

Breakdown of Mucin as Barrier to Digestive Enzymes in the Ischemic Rat Small Intestine

Loss of integrity of the epithelial/mucosal barrier in the small intestine has been associated with different pathologies that originate and/or develop in the gastrointestinal tract. We showed recently that mucin, the main protein in the mucus layer, is disrupted during early periods of intestinal ischemia. This event is accompanied by entry of pancreatic digestive enzymes into the intestinal wall. We hypothesize that the mucin-containing mucus layer is the main barrier preventing digestive enzymes from contacting the epithelium. Mucin breakdown may render the epithelium accessible to pancreatic enzymes, causing its disruption and increased permeability. The objective of this study was to investigate the role of mucin as a protection for epithelial integrity and function. A rat model of 30 min splanchnic arterial occlusion (SAO) was used to study the degradation of two mucin isoforms (mucin 2 and 13) and two epithelial membrane proteins (E-cadherin and toll-like receptor 4, TLR4). In addition, the role of digestive enzymes in mucin breakdown was assessed in this model by luminal inhibition with acarbose, tranexamic acid, or nafamostat mesilate. Furthermore, the protective effect of the mucin layer against trypsin-mediated disruption of the intestinal epithelium was studied in vitro. Rats after SAO showed degradation of mucin 2 and fragmentation of mucin 13, which was not prevented by protease inhibition. Mucin breakdown was accompanied by increased intestinal permeability to FITC-dextran as well as degradation of E-cadherin and TLR4. Addition of mucin to intestinal epithelial cells in vitro protected against trypsin-mediated degradation of E-cadherin and TLR4 and reduced permeability of FITC-dextran across the monolayer. These results indicate that mucin plays an important role in the preservation of the mucosal barrier and that ischemia but not digestive enzymes disturbs mucin integrity, while digestive enzymes actively mediate epithelial cell disruption

Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review

<p>Abstract</p> <p>Background</p> <p>Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps.</p> <p>Methods</p> <p>We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps.</p> <p>Results</p> <p>Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy.</p> <p>Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies.</p> <p>Conclusions</p> <p>Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.</p

Towards a resolution of some outstanding issues in transitive research: an empirical test on middle childhood

Transitive Inference (deduce B > D from B > C and C > D) can help us to understand other areas of sociocognitive development. Across three experiments, learning, memory, and the validity of two transitive paradigms were investigated. In Experiment 1 (N = 121), 7-year-olds completed a three-term nontraining task or a five-term task requiring extensive-training. Performance was superior on the three-term task. Experiment 2 presented 5–10-year-olds with a new five-term task, increasing learning opportunities without lengthening training (N = 71). Inferences improved, suggesting children can learn five-term series rapidly. Regarding memory, the minor (CD) premise was the best predictor of BD-inferential performance in both task-types. However, tasks exhibited different profiles according to associations between the major (BC) premise and BD inference, correlations between the premises, and the role of age. Experiment 3 (N = 227) helped rule out the possible objection that the above findings simply stemmed from three-term tasks with real objects being easier to solve than computer-tasks. It also confirmed that, unlike for five-term task (Experiments 1 & 2), inferences on three-term tasks improve with age, whether the age range is wide (Experiment 3) or narrow (Experiment 2). I conclude that the tasks indexed different routes within a dual-process conception of transitive reasoning: The five-term tasks indexes Type 1 (associative) processing, and the three-term task indexes Type 2 (analytic) processing. As well as demonstrating that both tasks are perfectly valid, these findings open up opportunities to use transitive tasks for educability, to investigate the role of transitivity in other domains of reasoning, and potentially to benefit the lived experiences of persons with developmental issues

EVOTECH® endoscope cleaner and reprocessor (ECR) simulated-use and clinical-use evaluation of cleaning efficacy

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to perform simulated-use testing as well as a clinical study to assess the efficacy of the EVOTECH^®Endoscope Cleaner and Reprocessor (ECR) cleaning for flexible colonoscopes, duodenoscopes, gastroscopes and bronchoscopes. The main aim was to determine if the cleaning achieved using the ECR was at least equivalent to that achieved using optimal manual cleaning.</p> <p>Methods</p> <p>Simulated-use testing consisted of inoculating all scope channels and two surface sites with Artificial Test Soil (ATS) containing 10⁸cfu/mL of <it>Enterococcus faecalis, Pseudomonas aeruginosa </it>and <it>Candida albicans</it>. Duodenoscopes, colonoscopes, and bronchoscopes (all Olympus endoscopes) were included in the simulated use testing. Each endoscope type was tested in triplicate and all channels and two surface sites were sampled for each scope. The clinical study evaluated patient-used duodenoscopes, bronchoscopes, colonoscopes, and gastroscopes (scopes used for emergency procedures were excluded) that had only a bedside flush prior to being processed in the ECR (i.e. no manual cleaning). There were 10 to 15 endoscopes evaluated post-cleaning and to ensure the entire ECR cycle was effective, 5 endoscopes were evaluated post-cleaning and post-high level disinfection. All channels and two external surface locations were sampled to evaluate the residual organic and microbial load. Effective cleaning of endoscope surfaces and channels was deemed to have been achieved if there was < 6.4 μg/cm²of residual protein, < 1.8 μg/cm²of residual hemoglobin and < 4 Log₁₀viable bacteria/cm². Published data indicate that routine manual cleaning can achieve these endpoints so the ECR cleaning efficacy must meet or exceed these to establish that the ECR cleaning cycle could replace manual cleaning</p> <p>Results</p> <p>In the clinical study 75 patient-used scopes were evaluated post cleaning and 98.8% of surfaces and 99.7% of lumens met or surpassed the cleaning endpoints set for protein, hemoglobin and bioburden residuals. In the simulated-use study 100% of the Olympus colonoscopes, duodenoscopes and bronchoscopes evaluated met or surpassed the cleaning endpoints set for protein, and bioburden residuals (hemoglobin was not evaluated).</p> <p>Conclusions</p> <p>The ECR cleaning cycle provides an effective automated approach that ensures surfaces and channels of flexible endoscopes are adequately cleaned after having only a bedside flush but no manual cleaning. It is crucial to note that endoscopes used for emergency procedures or where reprocessing is delayed for more than one hour MUST still be manually cleaned prior to placing them in the ECR.</p

HER-2 overexpression differentially alters transforming growth factor-β responses in luminal versus mesenchymal human breast cancer cells

INTRODUCTION: Amplification of the HER-2 receptor tyrosine kinase has been implicated in the pathogenesis and aggressive behavior of approximately 25% of invasive human breast cancers. Clinical and experimental evidence suggest that aberrant HER-2 signaling contributes to tumor initiation and disease progression. Transforming growth factor beta (TGF-β) is the dominant factor opposing growth stimulatory factors and early oncogene activation in many tissues, including the mammary gland. Thus, to better understand the mechanisms by which HER-2 overexpression promotes the early stages of breast cancer, we directly assayed the cellular and molecular effects of TGF-β1 on breast cancer cells in the presence or absence of overexpressed HER-2. METHODS: Cell proliferation assays were used to determine the effect of TGF-β on the growth of breast cancer cells with normal or high level expression of HER-2. Affymetrix microarrays combined with Northern and western blot analysis were used to monitor the transcriptional responses to exogenous TGF-β1 in luminal and mesenchymal-like breast cancer cells. The activity of the core TGF-β signaling pathway was assessed using TGF-β1 binding assays, phospho-specific Smad antibodies, immunofluorescent staining of Smad and Smad DNA binding assays. RESULTS: We demonstrate that cells engineered to over-express HER-2 are resistant to the anti-proliferative effect of TGF-β1. HER-2 overexpression profoundly diminishes the transcriptional responses induced by TGF-β in the luminal MCF-7 breast cancer cell line and prevents target gene induction by a novel mechanism that does not involve the abrogation of Smad nuclear accumulation, DNA binding or changes in c-myc repression. Conversely, HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-β induced pro-invasive and pro-metastatic gene signature. CONCLUSION: HER-2 overexpression promotes the growth and malignancy of mammary epithelial cells, in part, by conferring resistance to the growth inhibitory effects of TGF-β. In contrast, HER-2 and TGF-β signaling pathways can cooperate to promote especially aggressive disease behavior in the context of a highly invasive breast tumor model