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1.  Perceived risks and benefits of cigarette smoking among Nepalese adolescents: a population-based cross-sectional study 
BMC Public Health  2013;13:187.
Background
The perceived risks and benefits of smoking may play an important role in determining adolescents’ susceptibility to initiating smoking. Our study examined the perceived risks and benefits of smoking among adolescents who demonstrated susceptibility or non susceptibility to smoking initiation.
Methods
In October–November 2011, we conducted a population-based cross-sectional study in Jhaukhel and Duwakot Villages in Nepal. Located in the mid-hills of Bhaktapur District, 13 kilometers east of Kathmandu, Jhaukhel and Duwakot represent the prototypical urbanizing villages that surround Nepal’s major urban centers, where young people have easy access to tobacco products and are influenced by advertising. Jhaukhel and Duwakot had a total population of 13,669, of which 15% were smokers. Trained enumerators used a semi-structured questionnaire to interview 352 randomly selected 14- to 16-year-old adolescents. The enumerators asked the adolescents to estimate their likelihood (0%–100%) of experiencing various smoking-related risks and benefits in a hypothetical scenario.
Results
Principal component analysis extracted four perceived risk and benefit components, excluding addiction risk: (i) physical risk I (lung cancer, heart disease, wrinkles, bad colds); (ii) physical risk II (bad cough, bad breath, trouble breathing); (iii) social risk (getting into trouble, smelling like an ashtray); and (iv) social benefit (looking cool, feeling relaxed, becoming popular, and feeling grown-up). The adjusted odds ratio of susceptibility increased 1.20-fold with each increased quartile in perception of physical Risk I. Susceptibility to smoking was 0.27- and 0.90-fold less among adolescents who provided the highest estimates of physical Risk II and social risk, respectively. Similarly, susceptibility was 2.16-fold greater among adolescents who provided the highest estimates of addiction risk. Physical risk I, addiction risk, and social benefits of cigarette smoking related positively, and physical risk II and social risk related negatively, with susceptibility to smoking.
Conclusion
To discourage or prevent adolescents from initiating smoking, future intervention programs should focus on communicating not only the health risks but also the social and addiction risks as well as counteract the social benefits of smoking.
doi:10.1186/1471-2458-13-187
PMCID: PMC3599383  PMID: 23452549
Susceptibility to smoking; Physical risks; Social risks; Addiction risk; Social benefits
2.  High effective coverage of vector control interventions in children after achieving low malaria transmission in Zanzibar, Tanzania 
Malaria Journal  2013;12:38.
Background
Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission.
Methods
A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases.
Results
Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage.
Conclusions
While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the interventions and recognized the value of sustaining their use. Thus, sustaining high effective coverage of vector control interventions, which is crucial for reaching malaria elimination in Zanzibar, can be achieved by maintaining effective delivery of these interventions.
doi:10.1186/1475-2875-12-38
PMCID: PMC3564714  PMID: 23360479
3.  Breastfeeding practices in urban and rural Vietnam 
BMC Public Health  2012;12:964.
Background
The aim of this study was to describe and compare breastfeeding practices in rural and urban areas of Vietnam and to study associations with possibly influencing person and household factors. This type of study has not been conducted in Vietnam before.
Methods
Totally 2,690 children, born from 1st March 2008 to 30th June 2010 in one rural and one urban Health and Demographic Surveillance Site, were followed from birth to the age of 12 months. Information about demography, economy and education for persons and households was obtained from household surveys. Standard statistical methods including survival and regression analyses were used.
Results
Initiation of breastfeeding during the first hour of life was more frequent in the urban area compared to the rural (boys 40% vs. 35%, girls 49% vs. 40%). High birth weight and living in households with large number of assets significantly increased the probability for early initiation of breastfeeding. Exclusive breastfeeding at three months of age was more commonly reported in the rural than in the urban area (boys 58% vs. 46%, girls 65% vs. 53%). The duration of exclusive breastfeeding as well as of any breastfeeding was longer in the rural area than in the urban area (medians for boys 97 days vs. 81 days, for girls 102 days vs. 91 days). The percentages of children with exclusive breastfeeding lasting at least 6 months, as recommended by WHO, were low in both areas. The duration of exclusive breastfeeding was significantly shorter for mothers with three or more antenatal care visits or Caesarean section in both areas. High education level of mothers was associated with longer duration of exclusive breastfeeding in the rural area. No significant associations were found between duration of exclusive breastfeeding and mother’s age, household economy indicators or household size.
Conclusion
Intervention programs with the aim to promote breastfeeding are needed. Mothers should particularly be informed about the importance of starting breastfeeding early and to prolong exclusive breastfeeding. In order to reach the WHO recommendation of six months exclusive breastfeeding, we propose an extended maternity leave legislation to at least six months.
doi:10.1186/1471-2458-12-964
PMCID: PMC3503814  PMID: 23140543
Breastfeeding; Urban; Rural; Hanoi; Vietnam
4.  Dengue vector management using insecticide treated materials and targeted interventions on productive breeding-sites in Guatemala 
BMC Public Health  2012;12:931.
Background
In view of the epidemiological expansion of dengue worldwide and the availability of new tools and strategies particularly for controlling the primary dengue vector Aedes aegypti, an intervention study was set up to test the efficacy, cost and feasibility of a combined approach of insecticide treated materials (ITMs) alone and in combination with appropriate targeted interventions of the most productive vector breeding-sites.
Methods
The study was conducted as a cluster randomized community trial using “reduction of the vector population” as the main outcome variable. The trial had two arms: 10 intervention clusters (neighborhoods) and 10 control clusters in the town of Poptun Guatemala. Activities included entomological assessments (characteristics of breeding-sites, pupal productivity, Stegomyia indices) at baseline, 6 weeks after the first intervention (coverage of window and exterior doorways made of PermaNet 2.0 netting, factory treated with deltamethrin at 55 mg/m2, and of 200 L drums with similar treated material) and 6 weeks after the second intervention (combination of treated materials and other suitable interventions targeting productive breeding-sites i.e larviciding with Temephos, elimination etc.). The second intervention took place 17 months after the first intervention. The insecticide residual activity and the insecticidal content were also studied at different intervals. Additionally, information about demographic characteristics, cost of the intervention, coverage of houses protected and satisfaction in the population with the interventions was collected.
Results
At baseline (during the dry season) a variety of productive container types for Aedes pupae were identified: various container types holding >20 L, 200 L drums, washbasins and buckets (producing 83.7% of all pupae). After covering 100% of windows and exterior doorways and a small number of drums (where the commercial cover could be fixed) in 970 study households, tropical rains occurred in the area and lead to an increase of the vector population, more pronounced (but statistically not significant) in the control arm than in the intervention arm. In the second intervention (17 months later and six weeks after implementing the second intervention) the combined approach of ITMs and a combination of appropriate interventions against productive containers (Temephos in >200 L water drums, elimination of small discarded tins and bottles) lead to significant differences on reductions of the total number of pupae (P = 0.04) and the House index (P = 0.01) between intervention and control clusters, and to borderline differences on reductions of the Pupae per Person and Breteau indices (P = 0.05). The insecticide residual activity on treated curtains was high until month 18 but the chemical concentration showed a high variability. The cost per house protected with treated curtains and drum covers and targeting productive breeding-sites of the dengue vector was $ 5.31 USD. The acceptance of the measure was generally high, particularly in families who had experienced dengue.
Conclusion
Even under difficult environmental conditions (open houses, tropical rainfall, challenging container types mainly in the peridomestic environment) the combination of insecticide treated curtains and to a less extent drum covers and interventions targeting the productive container types can reduce the dengue vector population significantly.
doi:10.1186/1471-2458-12-931
PMCID: PMC3533994  PMID: 23110515
Dengue vectors; Insecticide treated materials; Targeted interventions; Guatemala
5.  Establishing a health demographic surveillance site in Bhaktapur district, Nepal: initial experiences and findings 
BMC Research Notes  2012;5:489.
Background
A health demographic surveillance system (HDSS) provides longitudinal data regarding health and demography in countries with coverage error and poor quality data on vital registration systems due to lack of public awareness, inadequate legal basis and limited use of data in health planning. The health system in Nepal, a low-income country, does not focus primarily on health registration, and does not conduct regular health data collection. This study aimed to initiate and establish the first HDSS in Nepal.
Results
We conducted a baseline survey in Jhaukhel and Duwakot, two villages in Bhaktapur district. The study surveyed 2,712 households comprising a total population of 13,669. The sex ratio in the study area was 101 males per 100 females and the average household size was 5. The crude birth and death rates were 9.7 and 3.9/1,000 population/year, respectively. About 11% of births occurred at home, and we found no mortality in infants and children less than 5 years of age. Various health problems were found commonly and some of them include respiratory problems (41.9%); headache, vertigo and dizziness (16.7%); bone and joint pain (14.4%); gastrointestinal problems (13.9%); heart disease, including hypertension (8.8%); accidents and injuries (2.9%); and diabetes mellitus (2.6%). The prevalence of non-communicable disease (NCD) was 4.3% (95% CI: 3.83; 4.86) among individuals older than 30 years. Age-adjusted odds ratios showed that risk factors, such as sex, ethnic group, occupation and education, associated with NCD.
Conclusion
Our baseline survey demonstrated that it is possible to collect accurate and reliable data in a village setting in Nepal, and this study successfully established an HDSS site. We determined that both maternal and child health are better in the surveillance site compared to the entire country. Risk factors associated with NCDs dominated morbidity and mortality patterns.
doi:10.1186/1756-0500-5-489
PMCID: PMC3494612  PMID: 22950751
6.  Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings 
Background
The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.
Methods/Design
Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.
Discussion
In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improves maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.
doi:10.1186/1471-2393-12-89
PMCID: PMC3500715  PMID: 22943425
Pregnancy Registry; Congenital anomaly; Pharmacovigilance; Teratogenicity; Drug exposure; Antiretrovirals; Antimalarials; Birth defects; Neonates; Safety; Resource-limited settings
7.  Alcohol environment, gender and nonfatal injuries in young people. An ecological study of fourteen Swedish municipalities (2000–2005) 
Background
Sweden has had a restrictive alcohol policy, but there are gender and geographical differences in alcohol consumption and injury rates within the country. Whether and how the Swedish alcohol environment influences gender differences in injuries in young people is still unclear. Thus, the aim of this study was to analyse the associations between the local alcohol environment and age- and gender-specific nonfatal injury rates in people up to 24 years in Sweden.
Methods
The local alcohol environment from 14 municipalities was studied using indicators of alcohol access, alcohol consumption and alcohol-related crimes. A comprehensive health care register of nonfatal injuries was used to estimate mean annual rates of nonfatal injuries by gender and age group (2000–2005). Pearson’s correlation coefficients were used to analyse linear associations.
Results
Associations were shown for both alcohol access and alcohol consumption with injury rates in boys aged 13–17 years; no other associations were observed between alcohol access or per capita alcohol consumption and nonfatal childhood injuries. The prevalence of crimes against alcohol laws was associated with injury rates in children of both genders aged 6–17 years.
Conclusions
This study found no strong area-level associations between alcohol and age and gender specific nonfatal injuries in young people. Further, the strength of the area-level associations varied by age, gender and type of indicator used to study the local alcohol environment.
doi:10.1186/1747-597X-7-36
PMCID: PMC3489536  PMID: 22908846
Children; Young adults; Alcohol access; Per capita alcohol consumption; Crimes against alcohol laws; Nonfatal injuries; Sweden; Municipality level; Gender
8.  Percentage of Patients with Preventable Adverse Drug Reactions and Preventability of Adverse Drug Reactions – A Meta-Analysis 
PLoS ONE  2012;7(3):e33236.
Background
Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients.
Methods
Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO’s or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted.
Results
Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2–3.2%) had preventable adverse drug reactions and 52% (95% CI: 42–62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1–51%) had preventable adverse drug reactions and 45% (95% CI: 33–58%) of adverse drug reactions were preventable.
Conclusions
This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research.
doi:10.1371/journal.pone.0033236
PMCID: PMC3305295  PMID: 22438900
9.  Physical growth during the first year of life. A longitudinal study in rural and urban areas of Hanoi, Vietnam 
BMC Pediatrics  2012;12:26.
Background
Good infant growth is important for future health. Assessing growth is common in pediatric care all over the world, both at the population and individual level. There are few studies of birth weight and growth studies comparing urban and rural communities in Vietnam. The first aim is to describe and compare the birth weight distributions and physical growth (weight and length) of children during their first year in one rural and one urban area of Hanoi Vietnam. The second aim is to study associations between the anthropometric outcomes and indicators of the economic and educational situations.
Methods
Totally 1,466 children, born from 1st March, 2009 to June 2010, were followed monthly from birth to 12 months of age in two Health and Demographic Surveillance Sites; one rural and one urban. In all, 14,199 measurements each of weight and length were made. Birth weight was recorded separately. Information about demographic conditions, education, occupation and economic conditions of persons and households was obtained from household surveys. Fractional Polynomial models and standard statistical methods were used for description and analysis.
Results
Urban infants have higher birth weight and gain weight faster than rural infants. The mean birth weight for urban boys and girls were 3,298 grams and 3,203 grams as compared to 3,105 grams and 3,057 grams for rural children. At 90 days, the urban boys were estimated to be 4.1% heavier than rural boys. This difference increased to 7.2% at 360 days. The corresponding difference for girls was 3.4% and 10.5%. The differences for length were comparatively smaller. Both birth weight and growth were statistically significantly and positively associated with economic conditions and mother education.
Conclusion
Birth weight was lower and the growth, weight and length, considerably slower in the rural area, for boys as well as for girls. The results support the hypothesis that the rather drastic differences in maternal education and economic conditions lead to poor nutrition for mothers and children in turn causing inferior birth weight and growth.
doi:10.1186/1471-2431-12-26
PMCID: PMC3372429  PMID: 22409903
10.  Factors associated with antenatal care adequacy in rural and urban contexts-results from two health and demographic surveillance sites in Vietnam 
Background
Antenatal Care (ANC) is universally considered important for women and children. This study aims to identify factors, demographic, social and economic, possibly associated with three ANC indicators: number of visits, timing of visits and content of services. The aim is also to compare the patterns of association of such factors between one rural and one urban context in northern Vietnam.
Methods
Totally 2,132 pregnant women were followed from identification of pregnancy until birth in two Health and Demographic Surveillance Sites (HDSS). Information was obtained through quarterly face to face interviews.
Results
Living in the rural area was significantly associated with lower adequate use of ANC compared to living in the urban area, both regarding quantity (number and timing of visits) and content. Low education, living in poor households and exclusively using private sector ANC in both sites and self employment, becoming pregnant before 25 years of age and living in poor communities in the rural area turned out to increase the risk for overall inadequate ANC. High risk pregnancy could not be demonstrated to be associated with ANC adequacy in either site. The medical content of services offered was often inadequate, in relation to the national recommendations, especially in the private sector.
Conclusion
Low education, low economic status, exclusive use of private ANC and living in rural areas were main factors associated with risk for overall inadequate ANC use as related to the national recommendations. Therefore, interventions focussing on poor and less educated women, especially in rural areas should be prioritized. They should focus the importance of early attendance of ANC and sufficient use of core services. Financial support for poor and near poor women should be considered. Providers of ANC should be educated and otherwise influenced to provide sufficient core services. Adherence to ANC content guidelines must be improved through enhanced supervision, particularly in the private sector.
doi:10.1186/1472-6963-12-40
PMCID: PMC3305637  PMID: 22335834
Antenatal care; Socio-economic determinants; Adequacy; Urban and rural; Vietnam
11.  Drug resistance patterns and virus re-suppression among HIV-1 subtype C infected patients receiving non-nucleoside reverse transcriptase inhibitors in South Africa 
Journal of AIDS & clinical research  2011;2(117):1000117.
Background
Emergence of HIV-1 drug resistance is at times an inevitable and anticipated consequence of antiretroviral therapy (ART) failure. We examined drug resistance patterns and virus re-suppression among subtype C-infected South African patients receiving first-line ART.
Methods
Treatment records of 431 patients on NNRTI-containing regimens for a median of 45 months were analyzed. Patients with viral load (VL) >400 copies/mL were followed and drug resistance mutations (DRM) were re-assessed. Associations between clinical/demographic measures and drug resistance/virologic outcomes were examined using Fisher exact and ordinal and logistic regression.
Results
Ten percent of patients (43/431) were viremic at enrollment (98% previously suppressed); sequences were obtained from 38/43. Of those, 82% had 1–7 DRM. In bivariate analysis remote exposure to single-dose nevirapine or prior ART; higher CD4 counts; lower VL; and >6 months of virologic failure were significantly associated with number of DRM. Of 25 viremic patients followed for a median of 8 months on a continued first-line regimen, 12 (48%) re-suppressed, six with K103N and three with M184V. Thirteen (52%) had continued virologic failure which was significantly associated with detectable VL>6 months prior to enrollment and number of DRM.
Conclusion
Among these HIV-1 subtype C-infected patients, DRM numbers and patterns were associated with prior exposure to sub-optimal ART, adherence and duration of virologic failure. Viral re-suppression in the presence of K103N and M184V challenges assumptions about drug resistance. In resource-limited settings, where genotyping and alternative drug options are unavailable, continuing first-line treatment, reinforcing adherence and regular virologic monitoring may be effective even after virologic failure.
doi:10.4172/2155-6113.1000117
PMCID: PMC3174802  PMID: 21927716
HIV-1; Subtype C; drug resistance; mutations; NNRTI; first-line ART; South Africa; ART experienced
12.  nViremia and drug resistance among HIV-1 patients on antiretroviral treatment – a cross-sectional study in Soweto, South Africa 
AIDS (London, England)  2010;24(11):1679-1687.
Background:
We assessed risk factors for viremia and drug resistance (DR) among long-term recipients of antiretroviral therapy (ART) in South Africa.
Methods:
In 2008, we conducted a cross-sectional study among patients receiving ART for ≥12 months. Genotypic resistance testing was performed on individuals with a viral load >400 RNA copies/ml. Multiple logistic regression analysis was used to assess associations.
Results:
Of 998 subjects, 75% were women with a median age of 41. Most (64%) had been on treatment for >3 years. The prevalence of viremia was 14% (n=139); 12% (102/883) on first-line (i.e. NNRTI based regimen) and 33% (37/115) on second-line (i.e. PI based regimen) ART. Of viremic patients, 78% had DR mutations. For NRTIs, NNRTIs and PIs the prevalence of mutations was 64%, 81% and 2% among first-line and 29%, 54% and 6% among second-line failures respectively. M184V/I, K103N and V106A/M were the most common mutations.
Significant risk factors associated with viremia on first-line included concurrent tuberculosis treatment (OR 6.4, 2.2-18.8, p<0.01) and a recent history of poor adherence (OR 2.7, 1.3-5.6, p=0.01). Among second-line failures, attending a public clinic (OR 4.6, 1.8-11.3, p<0.01) and not having a refrigerator at home (OR 6.7, 1.2-37.5, p=0.03) were risk factors for virological failure.
Conclusions:
Risk factors for viral failure were line-regimen dependent. Second-line ART recipients had a higher rate of viremia, albeit with infrequent PI DR mutations. Measures to maintain effective virologic suppression should include increased adherence counseling, attention to concomitant tuberculosis treatment and heat-stable formulations of second-line ART regimens.
doi:10.1097/QAD.0b013e32833a097b
PMCID: PMC2894994  PMID: 20453629
Antiretroviral therapy; HIV; adherence; HIV drug resistance; South Africa; Viral failure
13.  Malaria Rapid Testing by Community Health Workers Is Effective and Safe for Targeting Malaria Treatment: Randomised Cross-Over Trial in Tanzania 
PLoS ONE  2011;6(7):e19753.
Background
Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients.
Methodology/Principal Findings
Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029–0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8–97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients.
Conclusions/Significance
RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.
Trial registration
ClinicalTrials.gov NCT00301015
doi:10.1371/journal.pone.0019753
PMCID: PMC3130036  PMID: 21750697
14.  Novel Polymorphisms in Plasmodium falciparum ABC Transporter Genes Are Associated with Major ACT Antimalarial Drug Resistance 
PLoS ONE  2011;6(5):e20212.
Chemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial combination therapies. Alterations in the parasitic membrane proteins Pgh-1, PfCRT and PfMRP1 are believed to be major contributors to resistance through decreasing intracellular drug accumulation. The pfcrt, pfmdr1 and pfmrp1 genes were sequenced from a set of P.falciparum field isolates from the Thai-Myanmar border. In vitro drug susceptibility to artemisinin, dihydroartemisinin, mefloquine and lumefantrine were assessed. Positive correlations were seen between the in vitro susceptibility responses to artemisinin and dihydroartemisinin and the responses to the arylamino-alcohol quinolines lumefantrine and mefloquine. The previously unstudied pfmdr1 F1226Y and pfmrp1 F1390I SNPs were associated significantly with artemisinin, mefloquine and lumefantrine in vitro susceptibility. A variation in pfmdr1 gene copy number was also associated with parasite drug susceptibility of artemisinin, mefloquine and lumefantrine. Our work unveils new candidate markers of P. falciparum multidrug resistance in vitro, while contributing to the understanding of subjacent genetic complexity, essential for future evidence-based drug policy decisions.
doi:10.1371/journal.pone.0020212
PMCID: PMC3102103  PMID: 21633513
15.  Urban - rural disparities in antenatal care utilization: a study of two cohorts of pregnant women in Vietnam 
Background
The use of antenatal care (ANC) varies between countries and in different settings within each country. Most previous studies of ANC in Vietnam have been cross-sectional, and conducted in rural areas before the year 2000. This study aims to compare the pattern and the adequacy of ANC used in rural and urban Vietnam following two cohorts of pregnant women.
Methods
A comparative study with two cohorts comprising totally 2132 pregnant women were followed in two health and demographic surveillance sites, one rural and one urban in Hanoi province, Vietnam. The women were quarterly interviewed using a structured questionnaire until delivery. The primary information obtained was the number and the content of ANC visits.
Results
Almost all women reported some use of ANC. The average number of visits was much lower in the rural setting (4.4) than in the urban (7.7). In the rural area, 77.2% of women had at least three visits and 69.1% attended ANC during the first trimester. The corresponding percentages for the urban women were 97.2% and 97.2%. Only 20.3% of the rural women compared to 81.1% of the urban women received all core ANC services. As a result, the adequate use of ANC was 5.2 times in the urban than in the rural setting (78.3% compared to 15.2%). Nearly all women received ultrasound examination during pregnancy with a mean value of 6.0 scans per woman in the urban area and 3.5 in the rural. Most rural women used ANC at commune health centres and private clinics while urban women mainly visited public hospitals. Expenditure related to ANC utilization for the urban women was 7.1 times that for the urban women.
Conclusion
The women in the rural area attended ANC later, had fewer visits and received much fewer services than urban women. The large disparity in ANC adequacy between the two settings suggests special attention for the ANC programme in rural areas focusing on its content. Revision and enforcement of the national guidelines to improve the behaviour and practice of both users and providers are necessary.
doi:10.1186/1472-6963-11-120
PMCID: PMC3224373  PMID: 21605446
Antenatal care; adequacy; disparities; urban - rural comparison; Vietnam
16.  Understanding the context of balanced scorecard implementation: a hospital-based case study in pakistan 
Background
As a response to a changing operating environment, healthcare administrators are implementing modern management tools in their organizations. The balanced scorecard (BSC) is considered a viable tool in high-income countries to improve hospital performance. The BSC has not been applied to hospital settings in low-income countries nor has the context for implementation been examined. This study explored contextual perspectives in relation to BSC implementation in a Pakistani hospital.
Methods
Four clinical units of this hospital were involved in the BSC implementation based on their willingness to participate. Implementation included sensitization of units towards the BSC, developing specialty specific BSCs and reporting of performance based on the BSC during administrative meetings. Pettigrew and Whipp's context (why), process (how) and content (what) framework of strategic change was used to guide data collection and analysis. Data collection methods included quantitative tools (a validated culture assessment questionnaire) and qualitative approaches including key informant interviews and participant observation.
Results
Method triangulation provided common and contrasting results between the four units. A participatory culture, supportive leadership, financial and non-financial incentives, the presentation of clear direction by integrating support for the BSC in policies, resources, and routine activities emerged as desirable attributes for BSC implementation. The two units that lagged behind were more involved in direct inpatient care and carried a considerable clinical workload. Role clarification and consensus about the purpose and benefits of the BSC were noted as key strategies for overcoming implementation challenges in two clinical units that were relatively ahead in BSC implementation. It was noted that, rather than seeking to replace existing information systems, initiatives such as the BSC could be readily adopted if they are built on existing infrastructures and data networks.
Conclusion
Variable levels of the BSC implementation were observed in this study. Those intending to apply the BSC in other hospital settings need to ensure a participatory culture, clear institutional mandate, appropriate leadership support, proper reward and recognition system, and sensitization to BSC benefits.
doi:10.1186/1748-5908-6-31
PMCID: PMC3080822  PMID: 21453449
17.  Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study 
Malaria Journal  2011;10:64.
Background
Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home.
Methods
An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961.
Results
A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p ≤ 0.046).
Conclusions
Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.
doi:10.1186/1475-2875-10-64
PMCID: PMC3065443  PMID: 21410954
18.  Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa 
PLoS ONE  2011;6(3):e17518.
Background
Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.
Methods
In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).
Results
After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).
Conclusion
One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure.
doi:10.1371/journal.pone.0017518
PMCID: PMC3052314  PMID: 21408071
19.  Adherence and virologic suppression during the first 24 weeks on antiretroviral therapy among women in Johannesburg, South Africa - a prospective cohort study 
BMC Public Health  2011;11:88.
Background
Adherence is a necessary part of successful antiretroviral treatment (ART). We assessed risk factors for incomplete adherence among a cohort of HIV-infected women initiating ART and examined associations between adherence and virologic response to ART.
Methods
A secondary data analysis was conducted on a cohort of 154 women initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART at a single site in Johannesburg, South Africa. Ninety women had been enrolled in a prevention of mother-to-child transmission (pMTCT) program and were exposed to single-dose nevirapine (sdNVP) >18 months earlier. Women were interviewed pre-treatment and clinical, virologic and adherence data were collected during follow-up to 24 weeks. Incomplete adherence to ART was defined as returning >5% of medications, estimated by pill counts at scheduled visits. Multivariable logistic regression analysis and unadjusted odds ratio (95%CI) were performed, using STATA/SE (ver 10.1).
Results
About half of the women (53%) were <30 years of age, 63% had <11 years of schooling, 69% were unemployed and 37% lived in a shack. Seven percent of women had a viral load >400 copies/ml at 24 weeks and 37% had incomplete adherence at one or more visits. Incomplete adherence was associated with less education (p = 0.01) and lack of financial support from a partner (p = 0.02) after adjustment for confounders. Only when adherence levels dropped below 80% was there a significant association with viremia in the group overall (p = 0.02) although adherence <95% was associated with viremia in the sdNVP-exposed group (p = 0.03). The main reasons for incomplete adherence were being away from home, busy with other things and forgetting to take their medication.
Conclusion
Virologic response to NNRTI-treatment in the cohort was excellent. However, women who received sdNVP were at greater risk of virologic failure when adherence was <95%. Women exposed to sdNVP, and those with less education and less social support may benefit from additional adherence counseling to ensure the long-term success of ART. More than 80% adherence may be sufficient to maintain virologic suppression on NNRTI-based regimens in the short-term, however complete adherence should be encouraged.
doi:10.1186/1471-2458-11-88
PMCID: PMC3046911  PMID: 21303548
20.  Provider performance in treating poor patients - factors influencing prescribing practices in lao PDR: a cross-sectional study 
Background
Out-of-pocket payments make up about 80% of medical care spending at hospitals in Laos, thereby putting poor households at risk of catastrophic health expenditure. Social security schemes in the form of community-based health insurance and health equity funds have been introduced in some parts of the country. Drug and Therapeutics Committees (DTCs) have been established to ensure rational use of drugs and improve quality of care. The objective was to assess the appropriateness and expenditure for treatment for poor patients by health care providers at hospitals in three selected provinces of Laos and to explore associated factors.
Methods
Cross-sectional study using four tracer conditions. Structured interviews with 828 in-patients at twelve provincial and district hospitals on the subject of insurance protection, income and expenditures for treatment, including informal payment. Evaluation of each patient's medical record for appropriateness of drug use using a checklist of treatment guidelines (maximum score = 10).
Results
No significant difference in appropriateness of care for patients at different income levels, but higher expenditures for patients with the highest income level. The score for appropriate drug use in insured patients was significantly higher than uninsured patients (5.9 vs. 4.9), and the length of stay in days significantly shorter (2.7 vs. 3.7). Insured patients paid significantly less than uninsured patients, both for medicines (USD 14.8 vs. 43.9) and diagnostic tests (USD 5.9 vs. 9.2). On the contrary the score for appropriateness of drug use in patients making informal payments was significantly lower than patients not making informal payments (3.5 vs. 5.1), and the length of stay significantly longer (6.8 vs. 3.2), while expenditures were significantly higher both for medicines (USD 124.5 vs. 28.8) and diagnostic tests (USD 14.1 vs. 7.7).
Conclusions
The lower expenditure for insured patients can help reduce the number of households experiencing catastrophic health expenditure. The positive effects of insurance schemes on expenditure and appropriate use of medicines may be associated with the long-term effects of promoting rational use of drugs, including support to active DTC work.
doi:10.1186/1472-6963-11-3
PMCID: PMC3022646  PMID: 21210989
21.  Who Gets Prompt Access to Artemisinin-Based Combination Therapy? A Prospective Community-Based Study in Children from Rural Kilosa, Tanzania 
PLoS ONE  2010;5(8):e12104.
Background
Effective and timely case management remains one of the fundamental pillars for control of malaria. Tanzania introduced artemisinin-combination therapy [ACT] for uncomplicated malaria; however, the policy change is challenged by limited availability of ACTs due to high cost. This study aimed to determine factors influencing prompt access to ACTs among febrile children in rural Kilosa, Tanzania.
Methods and Findings
In a community-based study, 1,235 randomly selected children under five were followed up weekly for six months, in 2008. Using a structured questionnaire, children's caretakers were asked about the child's febrile history in the last seven days, and treatment actions including timing, medicines used and source of care. Caretakers' knowledge about malaria and socioeconomic and demographic data were also obtained. About half of followed-up children had at least one episode of fever. Less than half (44.8%) of febrile children were taken to government facilities. Almost one-third (37.6%; 95% CI 33.1–42.1) of febrile children had prompt access to ACT. Care-seeking from a government facility was the overriding factor, increasing the likelihood of prompt access to an ACT 18 times (OR 17.7; 95% CI 10.55–29.54; adjusted OR 16.9; 95% CI 10.06–28.28). Caretakers from the better-off household (3rd–5th quintiles) were more likely to seek care from government facilities (OR 3.66; 95% CI 2.56–5.24; adjusted OR 1.80; 95% CI 1.18–2.76). The majority of antimalarials accessed by the poor were ineffective [86.0%; 295/343], however, they paid more for them (median Tsh 500) compared to the better-offs (median Tsh 0).
Conclusions
Prompt access to ACT among febrile children was unacceptably low, due mainly to limited availability of subsidised ACT at the location where most caretakers sought care. There is urgent need to accelerate implementation of strategies that will ensure availability of ACT at an affordable price in remote rural areas, where the burden of malaria is highest.
doi:10.1371/journal.pone.0012104
PMCID: PMC2938374  PMID: 20856897
22.  Forecasting drug utilization and expenditure in a metropolitan health region 
Background
New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011.
Methods
Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee.
Results
The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs.
Conclusions
The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new medicines and various ongoing healthcare reforms and activities to improve the quality and efficiency of prescribing. Nevertheless, we believe our model will be valuable as an early warning system to start developing guidance for new drugs including systems to monitor their effectiveness, safety and cost-effectiveness in clinical practice.
doi:10.1186/1472-6963-10-128
PMCID: PMC2893175  PMID: 20478043
23.  Socioeconomic determinants of psychotropic drug utilisation among elderly: a national population-based cross-sectional study 
BMC Public Health  2010;10:118.
Background
Psychotropic drugs are commonly utilised among the elderly. This study aimed to analyse whether two socioeconomic determinants - income and marital status - are associated with differences in utilisation of psychotropic drugs and potentially inappropriate psychotropic drugs among elderly in Sweden.
Methods
All individuals aged 75 years and older who had purchased a psychotropic drug in Sweden during 2006 were included (68.7% women, n = 384712). Data was collected from national individual-based registers. Outcome measures were utilisation of three or more psychotropic drugs and utilisation of potentially inappropriate psychotropic drugs, as classified by the Swedish National Board of Health and Welfare.
Results
Individuals with low income were more likely to utilise three or more psychotropic drugs compared to those with high income; adjusted odds ratio (aOR) 1.12 (95% confidence interval [CI] 1.10-1.14). The non-married had a higher probability for utilising three or more psychotropic drugs compared to the married (aOR 1.22; CI 1.20-1.25). The highest probability was observed among the divorced and the never married. Potentially inappropriate psychotropic drugs were more common among individuals with low compared to high income (aOR 1.14; CI 1.13-1.16). Compared to the married, potentially inappropriate psychotropic drug utilisation occurred more commonly among the non-married (aOR 1.08; CI 1.06-1.10). The never married and the divorced had the highest probability.
Conclusions
There was an association between socioeconomic determinants and psychotropic drug utilisation. The probability for utilising potentially inappropriate psychotropics was higher among individuals with low income and among the non-married.
doi:10.1186/1471-2458-10-118
PMCID: PMC2845562  PMID: 20214796
24.  Assessing agreement between malaria slide density readings 
Malaria Journal  2010;9:4.
Background
Several criteria have been used to assess agreement between replicate slide readings of malaria parasite density. Such criteria may be based on percent difference, or absolute difference, or a combination. Neither the rationale for choosing between these types of criteria, nor that for choosing the magnitude of difference which defines acceptable agreement, are clear. The current paper seeks a procedure which avoids the disadvantages of these current options and whose parameter values are more clearly justified.
Methods and Results
Variation of parasite density within a slide is expected, even when it has been prepared from a homogeneous sample. This places lower limits on sensitivity and observer agreement, quantified by the Poisson distribution. This means that, if a criterion of fixed percent difference criterion is used for satisfactory agreement, the number of discrepant readings is over-estimated at low parasite densities. With a criterion of fixed absolute difference, the same happens at high parasite densities. For an ideal slide, following the Poisson distribution, a criterion based on a constant difference in square root counts would apply for all densities. This can be back-transformed to a difference in absolute counts, which, as expected, gives a wider range of acceptable agreement at higher average densities. In an example dataset from Tanzania, observed differences in square root counts correspond to a 95% limits of agreement of -2,800 and +2,500 parasites/μl at average density of 2,000 parasites/μl, and -6,200 and +5,700 parasites/μl at 10,000 parasites/μl. However, there were more outliers beyond those ranges at higher densities, meaning that actual coverage of these ranges was not a constant 95%, but decreased with density. In a second study, a trial of microscopist training, the corresponding ranges of agreement are wider and asymmetrical: -8,600 to +5,200/μl, and -19,200 to +11,700/μl, respectively. By comparison, the optimal limits of agreement, corresponding to Poisson variation, are ± 780 and ± 1,800 parasites/μl, respectively. The focus of this approach on the volume of blood read leads to other conclusions. For example, no matter how large a volume of blood is read, some densities are too low to be reliably detected, which in turn means that disagreements on slide positivity may simply result from within-slide variation, rather than reading errors.
Conclusions
The proposed method defines limits of acceptable agreement in a way which allows for the natural increase in variability with parasite density. This includes defining the levels of between-reader variability, which are consistent with random variation: disagreements within these limits should not trigger additional readings. This approach merits investigation in other settings, in order to determine both the extent of its applicability, and appropriate numerical values for limits of agreement.
doi:10.1186/1475-2875-9-4
PMCID: PMC2817705  PMID: 20047679
25.  Chemical and environmental vector control as a contribution to the elimination of visceral leishmaniasis on the Indian subcontinent: cluster randomized controlled trials in Bangladesh, India and Nepal 
BMC Medicine  2009;7:54.
Background
Bangladesh, India and Nepal are working towards the elimination of visceral leishmaniasis (VL) by 2015. In 2005 the World Health Organization/Training in Tropical Diseases launched an implementation research programme to support integrated vector management for the elimination of VL from Bangladesh, India and Nepal. The programme is conducted in different phases, from proof-of-concept to scaling up intervention. This study was designed in order to evaluate the efficacy of the three different interventions for VL vector management: indoor residual spraying (IRS); long-lasting insecticide treated nets (LLIN); and environmental modification (EVM) through plastering of walls with lime or mud.
Methods
Using a cluster randomized controlled trial we compared three vector control interventions with a control arm in 96 clusters (hamlets or neighbourhoods) in each of the 4 study sites: Bangladesh (one), India (one) and Nepal (two). In each site four villages with high reported VL incidences were included. In each village six clusters and in each cluster five households were randomly selected for sand fly collection on two consecutive nights. Control and intervention clusters were matched with average pre-intervention vector densities.
In each site six clusters were randomly assigned to each of the following interventions: indoor residual spraying (IRS); long-lasting insecticide treated nets (LLIN); environmental management (EVM) or control. All the houses (50-100) in each intervention cluster underwent the intervention measures. A reduction of intra-domestic sand fly densities measured in the study households by overnight US Centres for Disease Prevention and Control light trap captures (that is the number of sand flies per trap per night) was the main outcome measure.
Results
IRS, and to a lesser extent EVM and LLINs, significantly reduced sand fly densities for at least 5 months in the study households irrespective of type of walls or whether or not people shared their house with cattle. IRS was effective in all sites but LLINs were only effective in Bangladesh and India. Mud plastering did not reduce sand fly density (Bangladesh study); lime plastering in India and one Nepali site, resulted in a significant reduction of sand fly density but not in the second Nepali site.
Conclusion
Sand fly control can contribute to the regional VL elimination programme; IRS should be strengthened in India and Nepal but in Bangladesh, where vector control has largely been abandoned during the last decades, the insecticide treatment of existing bed nets (coverage above 90% in VL endemic districts) could bring about an immediate reduction of vector populations; operational research to inform policy makers about the efficacious options for VL vector control and programme performance should be strengthened in the three countries.
doi:10.1186/1741-7015-7-54
PMCID: PMC2763005  PMID: 19804620

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