Early detection and intervention for young children with early developmental disabilities in Western Uganda: a mixed-methods evaluation.

BACKGROUND: Early support for children with developmental disabilities is crucial but frequently unavailable in low-resource settings. We conducted a mixed-methods evaluation to assess the feasibility, acceptability, and impact of a programme of early detection and intervention for young children with developmental disabilities in Western Uganda. METHODS: Early child development training for healthcare workers (HCWs) was implemented in three rural districts, and attendance was tracked. HCW knowledge and confidence were assessed pre-/post-intervention, and referral numbers tracked to evaluate impact. Facilitators were trained and mentored to deliver a participatory, group, early intervention programme (EIP) for young children with developmental disabilities and their families. Facilitators were tracked as they were identified, trained, and delivered the intervention, and attendance of families was tracked. Pre-/post-intervention assessments evaluated changes in family quality of life (PedsQL 2.0, Family Impact Module), and child nutritional outcomes. Focus group discussions with stakeholders also assessed feasibility, acceptability and impact. RESULTS: Overall, 93 HCWs from 45 healthcare facilities received training. In the pre-/post-evaluation, median knowledge and confidence scores increased significantly (from 4.0 to 7.0 and from 2.7 to 4.7, respectively (p < 0.001)). HCWs reported feeling empowered to refer and offer care for families with a young child with disability. Referral rates increased significantly from 148 to 251 per annum (70%; p = 0.03). Eleven EIP facilitators were trained, and all delivered the intervention; 84 families were enrolled, of which 78% attended at least 6 out of 10 modules. Amongst those with paired pre-/post-intervention data (n = 48), total family quality of life scores increased significantly (21%, p < 0.001). Improvements were seen across all domains of quality of life, with the largest impacts on emotional functioning and social functioning (p < 0.001). The programme was acceptable to caregivers and facilitators. Caregivers reported improved knowledge, family relationships, hope, emotional wellbeing, and reduced self-stigma. CONCLUSIONS: A programme of early detection and intervention for children with early developmental disabilities and their families was feasible and acceptable in a rural community-based Ugandan setting. HCW training positively impacted knowledge, confidence, attitudes, and referral rates. Families enrolled to the EIP reported significant improvements in quality of life. Important programmatic barriers identified included geographical spread, poverty, gender inequality, and stigma.

Association between cervical dysplasia and female genital schistosomiasis diagnosed by genital PCR in Zambian women.

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. METHODS: Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. RESULTS: VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). CONCLUSIONS: This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed.

Schistosoma mansoni-specific immune responses and allergy in Uganda.

Low allergy-related disease (ARD) prevalence in low-income countries may be partly attributed to helminth infections. In the Schistosoma mansoni (Sm)-endemic Lake Victoria islands (Uganda), we recently observed positive helminth-allergy associations, despite low ARD prevalence. To understand how Sm-induced cytokine and antibody profiles might influence allergic response profiles in this population, we assessed Schistosoma worm (SWA)- and egg antigen (SEA)-specific Th1 (IFN-γ), Th2 (IL-5, IL-13) and regulatory (IL-10) cytokine profiles (n = 407), and total (n = 471), SWA-, SEA- and allergen (house dust mite [HDM] and cockroach)-specific (as)IgE and IgG4 profiles (n = 2117) by ELISA. Wheeze was inversely associated with SWA-specific IFN-γ (P < .001) and IL-10 (P = .058), and SEA-specific IL-5 (P = .004). Conversely, having a detectable asIgE response was positively associated with SWA-specific IL-5 (P = .006) and IL-10 (P < .001). Total, SWA-, SEA- and allergen-specific IgE and IgG4 responses were higher among Sm Kato-Katz positive (SmKK+) and skin prick test (SPT)+ individuals compared to SmKK- and SPT- individuals. However, total and asIgG4/IgE ratios were lower among SPT+ and wheezing individuals. We conclude that, in this population, helminth-induced antibody and cytokine responses may underlie individual positive helminth-atopy associations, while the overall IgG4-IgE balance may contribute to the low overall prevalence of clinical allergies in such settings.

Helminths are positively associated with atopy and wheeze in Ugandan fishing communities: results from a cross-sectional survey.

BACKGROUND: Parasitic helminths are potent immunomodulators and chronic infections may protect against allergy-related disease and atopy. We conducted a cross-sectional survey to test the hypothesis that in heavily helminth-exposed fishing villages on Lake Victoria, Uganda, helminth infections would be inversely associated with allergy-related conditions. METHODS: A household survey was conducted as baseline to an anthelminthic intervention trial. Outcomes were reported wheeze in last year, atopy assessed both by skin prick test (SPT) and by the measurement of allergen-specific IgE to dust mites and cockroach in plasma. Helminth infections were ascertained by stool, urine and haemoparasitology. Associations were examined using multivariable regression. RESULTS: Two thousand three hundred and sixteen individuals were surveyed. Prevalence of reported wheeze was 2% in under-fives and 5% in participants ≥5 years; 19% had a positive SPT; median Dermatophagoides-specific IgE and cockroach-specific IgE were 1440 and 220 ng/ml, respectively. S. mansoni, N. americanus, S. stercoralis, T. trichiura, M. perstans and A. lumbricoides prevalence was estimated as 51%, 22%, 12%, 10%, 2% and 1%, respectively. S. mansoni was positively associated with Dermatophagoides-specific IgE [adjusted geometric mean ratio (aGMR) (95% confidence interval) 1.64 (1.23, 2.18)]; T. trichiura with SPT [adjusted odds ratio (aOR) 2.08 (1.38, 3.15)]; M. perstans with cockroach-specific IgE [aGMR 2.37 (1.39, 4.06)], A. lumbricoides with wheeze in participants ≥5 years [aOR 6.36 (1.10, 36.63)] and with Dermatophagoides-specific IgE [aGMR 2.34 (1.11, 4.95)]. No inverse associations were observed. CONCLUSIONS: Contrary to our hypothesis, we found little evidence of an inverse relationship between helminths and allergy-related outcomes, but strong evidence that individuals with certain helminths were more prone to atopy in this setting.

Persistence of long-distance, insect-mediated pollen movement for a tropical canopy tree species in remnant forest patches in an urban landscape.

As deforestation and urbanization continue at rapid rates in tropical regions, urban forest patches are essential repositories of biodiversity. However, almost nothing is known about gene flow of forest-dependent tree species in urban landscapes. In this study, we investigated gene flow in the insect-pollinated, wind-dispersed tropical tree Koompassia malaccensis in and among three remnant forest patches in the urbanized landscape of Singapore. We genotyped the vast majority of adults (N=179) and a large number of recruits (N=2103) with 8 highly polymorphic microsatellite markers. Spatial genetic structure of the recruit and adult cohorts was significant, showing routine gene dispersal distances of ~100-400 m. Parentage analysis showed that 97% of recruits were within 100 m of their mother tree, and a high frequency of relatively short-distance pollen dispersal (median ~143-187 m). Despite routine seed and pollen dispersal distances of within a few hundred meters, interpatch gene flow occurred between all patches and was dominated by pollen movement: parentage analysis showed 76 pollen versus 2 seed interpatch dispersal events, and the seedling neighborhood model estimated ~1-6% seed immigration and ~21-46% pollen immigration rates, depending on patch. In addition, the smallest patch (containing five adult K. malaccensis trees) was entirely surrounded by >2.5 km of 'impervious' substrate, yet had the highest proportional pollen and seed immigration estimates of any patch. Hence, contrary to our hypothesis, insect-mediated gene flow persisted across an urban landscape, and several of our results also parallel key findings from insect-pollinated canopy trees sampled in mixed agricultural-forest landscapes.

A framework for assessing supply-side wildlife conservation.

Market-based, supply-side interventions such as domestication, cultivation, and wildlife farming have been proposed as legal substitutes for wild-collected plants and animals in the marketplace. Based on the literature, we devised a list of the conditions under which supply-side interventions may yield positive conservation outcomes. We applied it to the trade of the orchid Rhynchostylis gigantea, a protected ornamental plant. We conducted a survey of R. gigantea at Jatujak Market in Bangkok, Thailand. Farmed (legal) and wild (illegal, protected) specimens of R. gigantea were sold side-by-side at market. These results suggest farmed specimens are not being substituted for wild plants in the marketplace. For any given set of physical plant characteristics (size, condition, flowers), the origin of the plants (wild vs. farmed) did not affect price. For all price classes, farmed plants were of superior quality to wild-collected plants on the basis of most physical variables. These results suggest wild and farmed specimens represent parallel markets and may not be substitutable goods. Our results with R. gigantea highlight a range of explanations for why supply-side interventions may lack effectiveness, for example, consumer preferences for wild-collected products and low financial incentives for farming. Our results suggest that market-based conservation strategies may not be effective by themselves and may be best utilized as supplements to regulation and education. This approach represents a broad, multidisciplinary evaluation of supply-side interventions that can be applied to other plant and animal species.

Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition.

Female genital schistosomiasis (FGS) results from egg-deposition in the female reproductive tract primarily by the waterborne parasite Schistosoma (S.) haematobium, and less commonly by Schistosoma (S.) mansoni. FGS affects an estimated 20-56 million women worldwide, mostly in sub-Saharan Africa. There is cross-sectional evidence of increased HIV-1 prevalence in schistosomiasis-infected women, but a causal relationship between FGS and either HIV-1 acquisition or transmission has not been fully established. Beyond the pathognomonic breach in the cervicovaginal barrier caused by FGS, this narrative review explores potential mechanisms for a synergistic relationship between S. haematobium infection, FGS, and HIV-1 acquisition through vaginal inflammation and target cell recruitment.

Is birth weight associated with blood pressure among African children and adolescents? A systematic review.

There is substantial evidence of an inverse association between birth weight and later blood pressure (BP) in populations from high-income countries, but whether this applies in low-income countries, where causes of low birth weight are different, is not certain. OBJECTIVE: We conducted a review of the evidence on the relationship between birth weight and BP among African children and adolescents. Medline, EMBASE, Global Health and Web of Science databases were searched for publications to October 2016. Papers reporting the relationship between birth weight and BP among African children and adolescents were assessed. Bibliographies were searched for further relevant publications. Selected papers were summarized following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. In total, 16 papers from 13 studies conducted in nine African countries (Nigeria, Republic of Seychelles, Gambia, Democratic Republic of Congo, Cameroon, South Africa, Algeria, Zimbabwe and Angola) were reviewed. Eight studies were cohorts, while five were cross-sectional. The relationship between birth weight and later BP varied with age of the participants. Studies in neonates showed a consistently positive association, while predominantly inverse associations were seen among children, and studies in adolescents were inconsistent. Based on the limited number of studies identified, the relationship between birth weight and later BP may vary with age in African children and adolescents. Not all studies adequately controlled for confounding, notably gender or age. Whether the inverse relationship between birth weight and BP in later life observed in Western settings is also seen in Africa remains unclear.

Completion of isoniazid preventive therapy among human immunodeficiency virus positive adults in urban Malawi.

SETTING: Despite worldwide scale-up of human immunodeficiency virus (HIV) care services, relatively few countries have implemented isoniazid preventive therapy (IPT). Among other programmatic concerns, IPT completion tends to be low, especially when not fully integrated into HIV care clinics. OBJECTIVE: To estimate non-completion of 6-month IPT and its predictors among HIV-positive adults aged 16 years. DESIGN: A prospective cohort study nested within a cluster-randomised trial of TB prevention was conducted between February 2012 and June 2014. IPT for 6 months was provided with pyridoxine at study clinics. Non-completion was defined as loss to follow-up (LTFU), death, active/presumptive TB or stopping IPT for any other reason. Random-effects logistic regression was used to determine predictors of non-completion. RESULTS: Of 1284 HIV-positive adults initiated on IPT, 885/1280 (69.1%) were female; the median CD4 count was 337 cells/µl (IQR 199-511); 320 (24.9%) did not complete IPT. After controlling for antiretroviral treatment status, IPT initiation year, age and sex, non-completion of IPT was associated with World Health Organization stage 3/4 (aOR 1.76, 95%CI 1.22-2.55), CD4 count 100-349 cells/µl (aOR 1.93, 95%CI 1.10-3.38) and any reported side effects (aOR 22.00, 95%CI 9.45-46.71). CONCLUSION: Completion of IPT was suboptimal. Interventions to further improve retention should target immunosuppressed HIV-positive adults and address side effects.

Indapamide in the stepped-care treatment of obese hypertensive patients.

A double-blind study was carried out in obese patients with moderately severe hypertension to assess the efficacy and tolerability of 2.5 mg indapamide as a once-a-day Step 1 drug compared to 50 mg hydrochlorothiazide also as a once-a-day Step 1 drug; to assess the efficacy and tolerability of a fixed daily dose of 2.5 mg indapamide administered concomitantly with methyldopa starting at 500 mg daily; and to compare the findings of efficacy and tolerability of 2.5 mg indapamide daily with those of 50 mg hydrochlorothiazide daily as Step 1 agents when methyldopa is the Step 2 drug. Twenty-nine patients completed the study and were evaluated. Nine patients achieved the study criterion of reduction of average standing diastolic pressure to 90 mmHg or less when treated with Step 1 medication only. Twenty patients required the addition of methyldopa to their Step 1 medication: 10 patients took 2.5 mg indapamide with an average constant daily dose of 1100 mg methyldopa and 10 patients took 50 mg hydrochlorothiazide with an average constant daily dose of 1575 mg methyldopa to achieve blood pressure control. All groups had mean diastolic pressure controlled at or below the 90 mmHg criterion during the period of constant methyldopa dosage for those patients who required Step 2 therapy. There were no significant differences between groups with respect to diastolic pressure during the constant dosage period. The indapamide patients required significantly (p less than 0.05) less methyldopa than did the hydrochlorothiazide patients in order to maintain satisfactory control of diastolic blood pressure. The number of responders was greater in the 2.5 mg indapamide + methyldopa group than it was in the 50 mg hydrochlorothiazide + methyldopa group, and responses were achieved more rapidly in the former group than in the latter. Indapamide (2.5 mg per day) was effective and well tolerated when used alone or as Step 1 medication in combination with methyldopa as Step 2 medication, and it compared favourably in this regard with hydrochlorothiazide.

Chlorthalidone-triamterene: a potassium-sparing diuretic combination for the treatment of oedema.

The efficacy of a once-daily combination of chlorthalidone 50 mg plus triamterene 50 mg or chlorthalidone 100 mg plus triamterene 100 mg was compared to that of chlorthalidone 50 mg or 100 mg. This double-blind study was carried out in eighty-eight patients over a treatment period of 12 weeks. All patients entered the active medication period of 12 weeks after a placebo run-in period of 3 to 7 days, during which pretibial or malleolar pitting oedema averaging 2 to 4 mm developed. All patients started at the lower doses, i.e. forty-one started on chlorthalidone 50 mg plus triamterene 50 mg and forty-seven started on chlorthalidone 50 mg. The protocol provided for doubling the dose (but not for reducing it thereafter) at any time during the 12-week period when control of oedema was deemed inadequate. Eight of the combination therapy patients and sixteen of those on chlorthalidone required the higher doses. By Week 12, 96% of the chlorthalidone plus triamterene patients and 100% of the chlorthalidone patients had shown a reduction of at least 2 mm in depth of pits, and 92% and 72%, respectively, had complete disappearance of oedema. The decreases in pitting oedema were paralleled by mean weight losses of 2.4 kg and 3.1 kg, respectively, for the combination treatment group and the chlorthalidone group. Average serum potassium levels throughout the 12-week treatment period were 3.70 mEq/L for the patients taking the combination compared to 3.41 mEq/L of those taking chlorthalidone.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. I.

Chlorthalidone 25 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 25 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reactions.

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. II.

Chlorthalidone 50 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 50 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reaction.

Effect of 1- and 4-minute treatments of topical fluorides on a composite resin.

The purpose of this in vitro study was to compare the effects of a 1-min immersion and of 4-min immersions in an acidulated phosphate fluoride (1.23% APF) foam, a 1.23% APF gel, a 2.0% sodium fluoride (NaF) gel, and water on surface topography and on weight of a composite resin (APH). Forty composite resin specimens were placed into eight groups (N = 5 each). For each treatment, a group of specimens was immersed for either 1 or 4 min (four 1-min immersions). Specimens were weighed before and after each immersion. The surface topography of two scanning electron micrographs of each specimen was scored visually by two investigators. Inter-rater reliability was r = 0.75 (intraclass correlation coefficient). There were no significant differences in the mean visual scores or weight among the 1-min immersion groups. Significantly greater surface changes and weight loss of this composite resin occurred following 4-min immersions in either 1.23% APF foam or gel as compared with those immersed in either 2.0% NaF gel or water (P 0.0001; one-way ANOVA, Tukey's Studentized Range Test).

Prognostic significance of folate metabolism polymorphisms for lung cancer.

Functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) of folate metabolism genes can influence the methylation of tumour suppressor genes, thereby potentially impacting on tumour behaviour. To investigate whether such polymorphisms influence lung cancer survival, we genotyped 14 nsSNPs mapping to methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2), methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non-small cell (NSCLC) and 154 with small cell lung cancer (SCLC). The most significant association detected was with MTHFS Thr202Ala, with carriers of variant alleles having a worse prognosis (hazard ratio (HR)=1.49; 95% confidence interval: 1.14-1.94). Associations were also detected between overall survival (OS) in SCLC and homozygosity for MTHFR 222Val (HR=1.92; 1.03-3.58) and between OS from NSCLC and MTRR 175Leu carrier status (HR=1.36; 1.06-1.75). While there is evidence that variation in the folate metabolism genes may influence prognosis from lung cancer, current data are insufficiently robust to distinguish individual patient outcome.

Further observations on the relationship between the FGFR4 Gly388Arg polymorphism and lung cancer prognosis.

The Gly388Arg polymorphism in the fibroblast growth factor receptor 4 (FGFR4) gene has been reported to influence prognosis in a wide variety of cancer types. To determine whether Gly388Arg is a marker for lung cancer prognosis, we genotyped 619 lung cancer patients with incident disease and examined the relationship between genotype and overall survival. While we employed a comprehensive set of statistical tests, including those sensitive to the detection of differences in early survival, our data provide little evidence to support the tenet that the FGFR4 Gly388Arg polymorphism is a clinically useful marker for lung cancer prognosis.

Case-control, kin-cohort and meta-analyses provide no support for STK15 F31I as a low penetrance colorectal cancer allele.

Recently, homozygosity for T91A single-nucleotide polymorphism (SNP) in the serine/threonine kinase (STK15) gene, which generates the substitution F31I has been proposed to increase the risk of a number of tumours including colorectal cancer (CRC). To further evaluate the relationship between STK15 F31I and risk of CRC, we genotyped 2558 CRC cases and 2680 controls for this polymorphism. We found no evidence that homozygosity for the STK15 31I genotype confers an increased risk of CRC (odds ratio=0.95, 95% confidence interval (CI): 0.74-1.24). We also conducted a kin-cohort analysis to assess risk among first-degree relatives of the CRC cases. The hazard ratio for I/I homozygotes compared to F/F homozygotes was 1.65 (95% CI: 0.39-3.17). A meta-analysis of our case-control data and three previous studies also provided no evidence of an elevated risk of CRC associated with homozygosity. These data provide no support for the hypothesis that sequence variation in STK15 defined by SNP F31I per se confers an elevated risk of CRC.

Multisectional mold for fabrication of prosthetic ears.

The use of a multisectional stone mold is advocated for the fabrication of prosthetic ears. Less force is required in the deflasking procedure with this technique, reducing the risk of fracturing the mold or tearing the prosthesis. This technique requires more time and care in the flasking procedure. Convergence of the sections is of particular importance. The potential for multiple section lines may result in a need for more surface finishing of the prosthesis.

Temporization of severely fractured vital anterior teeth.

The technique described offers the patient an esthetic temporary crown for a horizontally fractured vital anterior tooth without resorting to emergency root canal therapy or pins.