Armin Gemperli

Mapping malaria transmission in West and Central Africa

We have produced maps of Plasmodium falciparum malaria transmission in West and Central Africa using the Mapping Malaria Risk in Africa (MARA) database comprising all malaria prevalence surveys in these regions that could be geolocated. The 1846 malaria surveys analysed were carried out during different seasons, and were reported using different age groupings of the human population. To allow comparison between these, we used the Garki malaria transmission model to convert the malaria prevalence data at each of the 976 locations sampled to a single estimate of transmission intensity E, making use of a seasonality model based on Normalized Difference Vegetation Index (NDVI), temperature and rainfall data. We fitted a Bayesian geostatistical model to E using further environmental covariates and applied Bayesian kriging to obtain smooth maps of E and hence of age‐specific prevalence. The product is the first detailed empirical map of variations in malaria transmission intensity that includes Central Africa. It has been validated by expert opinion and in general confirms known patterns of malaria transmission, providing a baseline against which interventions such as insecticide‐treated nets programmes and trends in drug resistance can be evaluated. There is considerable geographical variation in the precision of the model estimates and, in some parts of West Africa, the predictions differ substantially from those of other risk maps. The consequent uncertainties indicate zones where further survey data are needed most urgently. Malaria risk maps based on compilations of heterogeneous survey data are highly sensitive to the analytical methodology.

Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta-epidemiological study

BACKGROUND Clinicians find standardized mean differences (SMDs) calculated from continuous outcomes difficult to interpret. Our objective was to determine the performance of methods in converting SMDs or means to odds ratios of treatment response and numbers needed to treat (NNTs) as more intuitive measures of treatment effect. METHODS Meta-epidemiological study of large-scale trials (≥ 100 patients per group) comparing active treatment with placebo, sham or non-intervention control. Trials had to use pain or global symptoms as continuous outcomes and report both the percentage of patients with treatment response and mean pain or symptom scores per group. For each trial, we calculated odds ratios of observed treatment response and NNTs and approximated these estimates from SMDs or means using all five currently available conversion methods by Hasselblad and Hedges (HH), Cox and Snell (CS), Furukawa (FU), Suissa (SU) and Kraemer and Kupfer (KK). We compared observed and approximated values within trials by deriving pooled ratios of odds ratios (RORs) and differences in NNTs. ROR <1 and positive differences in NNTs imply that approximations are more conservative than estimates calculated from observed treatment response. As measures of agreement, we calculated intraclass correlation coefficients. RESULTS A total of 29 trials in 13 654 patients were included. Four out of five methods were suitable (HH, CS, FU, SU), with RORs between 0.92 for SU [95% confidence interval (95% CI), 0.86-0.99] and 0.97 for HH (95% CI, 0.91-1.04) and differences in NNTs between 0.5 (95% CI, -0.1 to -1.6) and 1.3 (95% CI, 0.4-2.1). Intraclass correlation coefficients were ≥ 0.90 for these four methods, but ≤ 0.76 for the fifth method by KK (P for differences ≤ 0.027). CONCLUSIONS The methods by HH, CS, FU and SU are suitable to convert summary treatment effects calculated from continuous outcomes into odds ratios of treatment response and NNTs, whereas the method by KK is unsuitable.

Swiss national community survey on functioning after spinal cord injury: Protocol, characteristics of participants and determinants of non-response.

OBJECTIVE To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. DESIGN The survey consisted of 3 successive modules administered between September 2011 and March 2013. The first two modules queried demographics, lesion characteristics and key domains of functioning. The third module collected information on psychological personal factors and health behaviour; work integration; or health services and aging. PARTICIPANTS Community-dwelling persons with chronic spinal cord injury in Switzerland. METHODS Descriptive analyses of the recruitment process, participant characteristics, and correspondence between self-reported and clinical data. Determinants for participation and the impact of non-response on survey results were assessed. RESULTS Out of 3,144 eligible persons 1,549 participated in the first two modules (cumulative response rate 49.3%). Approximately three-quarters of participants were male, with a median age of 53 years, and 78% had traumatic spinal cord injury. Record-linkage with medical records demonstrated substantial agreement with self-reported demographic and lesion characteristics. A minimal non-response bias was found. CONCLUSIONS The community survey was effective in recruiting an unbiased sample, thus providing valuable information to study functioning, health maintenance, and quality of life in the Swiss SCI community.

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Design Systematic review and network meta-analysis using Bayesian statistics. Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome. Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy. Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.

Differences in Heart Rate Variability Associated with Long-Term Exposure to NO2

Background Heart rate variability (HRV), a measure of cardiac autonomic tone, has been associated with cardiovascular morbidity and mortality. Short-term studies have shown that subjects exposed to higher traffic-associated air pollutant levels have lower HRV. Objective Our objective was to investigate the effect of long-term exposure to nitrogen dioxide on HRV in the Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). Methods We recorded 24-hr electrocardiograms in randomly selected SAPALDIA participants ≥ 50 years of age. Other examinations included an interview investigating health status and measurements of blood pressure, body height, and weight. Annual exposure to NO2 at the address of residence was predicted by hybrid models (i.e., a combination of dispersion predictions, land-use, and meteorologic parameters). We estimated the association between NO2 and HRV in multivariable linear regression models. Complete data for analyses were available for 1,408 subjects. Results For women, but not for men, each 10-μg/m3 increment in 1-year averaged NO2 level was associated with a decrement of 3% (95% CI, −4 to −1) for the standard deviation of all normal-to-normal RR intervals (SDNN), −6% (95% CI, −11 to −1) for nighttime low frequency (LF), and −5% (95% CI, −9 to 0) for nighttime LF/high-frequency (HF) ratio. We saw no significant effect for 24-hr total power (TP), HF, LF, or LF/HF or for nighttime SDNN, TP, or HF. In subjects with self-reported cardiovascular problems, SDNN decreased by 4% (95% CI, −8 to −1) per 10-μg/m3 increase in NO2. Conclusions There is some evidence that long-term exposure to NO2 is associated with cardiac autonomic dysfunction in elderly women and in subjects with cardiovascular disease.

Prevalence of sarcoidosis in Switzerland is associated with environmental factors

The current study aimed to investigate incidence, prevalence and regional distribution of sarcoidosis in Switzerland with respect to environmental exposures. All sarcoidosis patients hospitalised between 2002 and 2005 were identified from the Swiss hospital statistics from the Swiss Federal Office for Statistics (Neuchâtel, Switzerland). Regional exposure characteristics included the regional distribution of different industrial sectors, agriculture and air quality. Co-inertia analysis, as well as a generalised linear model, was applied. The prevalence of “ever-in-life” diagnosed sarcoidosis, currently active sarcoidosis and sarcoidosis requiring hospitalisation was 121 (95% CI 93–149), 44 (95% CI 34–54) and 16 (95% CI 10–22) per 100,000 inhabitants, respectively. The mean annual incidence of sarcoidosis was 7 (95% CI 5–11) per 100,000 inhabitants. The regional workforce in the metal industry, water supply, air transport factories and the area of potato production, artificial meadows (grassland) and bread grains were positively associated with the frequency of sarcoidosis. The prevalence of sarcoidosis was higher than assumed based on former international estimates. Higher frequency was found in regions with metal industry and intense agriculture, especially production of potatoes, bread grains and artificial meadows.

Spatial Effects of the Social Marketing of Insecticide-Treated Nets on Malaria Morbidity.

Randomized controlled trials have shown that insecticide‐treated nets (ITNs) have an impact on both malaria morbidity and mortality. Uniformly high coverage of ITNs characterized these trials and this resulted in some protection of nearby non‐users of ITNs. We have now assessed the coverage, distribution pattern and resultant spatial effects in one village in Tanzania where ITNs were distributed in a social marketing programme. The prevalence of parasitaemia, mild anaemia (Hb <11 g/dl) and moderate/severe anaemia (Hb <8 g/dl) in children under five was assessed cross‐sectionally. Data on ownership of ITNs were collected and inhabitants’ houses were mapped. One year after the start of the social marketing programme, 52% of the children were using a net which had been treated at least once. The ITNs were rather homogeneously distributed throughout the village at an average density of about 118 ITNs per thousand population. There was no evidence of a pattern in the distribution of parasitaemia and anaemia cases, but children living in areas of moderately high ITN coverage were about half as likely to have moderate/severe anaemia (OR 0.5, 95% CI: 0.2, 0.9) and had lower prevalence of splenomegaly, irrespective of their net use. No protective effects of coverage were found for prevalence of mild anaemia nor for parasitaemia. The use of untreated nets had neither coverage nor short distance effects. More efforts should be made to ensure high coverage in ITNs programmes to achieve maximum benefit.

Integrating fragmented evidence by network meta-analysis: relative effectiveness of psychological interventions for adults with post-traumatic stress disorder.

BACKGROUND To summarize the available evidence on the effectiveness of psychological interventions for patients with post-traumatic stress disorder (PTSD). METHOD We searched bibliographic databases and reference lists of relevant systematic reviews and meta-analyses for randomized controlled trials that compared specific psychological interventions for adults with PTSD symptoms either head-to-head or against control interventions using non-specific intervention components, or against wait-list control. Two investigators independently extracted the data and assessed trial characteristics. RESULTS The analyses included 4190 patients in 66 trials. An initial network meta-analysis showed large effect sizes (ESs) for all specific psychological interventions (ESs between -1.10 and -1.37) and moderate effects of psychological interventions that were used to control for non-specific intervention effects (ESs -0.58 and -0.62). ES differences between various types of specific psychological interventions were absent to small (ES differences between 0.00 and 0.27). Considerable between-trial heterogeneity occurred (τ²= 0.30). Stratified analyses revealed that trials that adhered to DSM-III/IV criteria for PTSD were associated with larger ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in trials with adequate concealment of allocation and in large-sized trials. We found evidence for small-study bias. CONCLUSIONS Our findings show that patients with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit from different psychological interventions. We did not identify any intervention that was consistently superior to other specific psychological interventions. However, the robustness of evidence varies considerably between different psychological interventions for PTSD, with most robust evidence for cognitive behavioral and exposure therapies.

Ultrasonographic features of PMEL17 ( Silver ) mutant gene-associated multiple congenital ocular anomalies (MCOA) in Comtois and Rocky Mountain horses

OBJECTIVE (1) To describe the ultrasonographic appearance of multiple congenital ocular anomalies (MCOA) in the eyes of horses with the PMEL17 (Silver) mutant gene. (2) To compare the accuracy of B-mode ocular ultrasound to conventional direct ophthalmoscopy. ANIMALS STUDIED Sixty-seven Comtois and 18 Rocky Mountain horses were included in the study. PROCEDURES Horses were classified as being carriers or noncarriers of the PMEL17 mutant allele based on coat color or genetic testing. Direct ophthalmoscopy followed by standardized ultrasonographic examination was performed in all horses. RESULTS Seventy-five of 85 horses (88.24%) carried at least one copy of the Silver mutant allele. Cornea globosa, severe iridal hypoplasia, uveal cysts, cataracts, and retinal detachment could be appreciated with ultrasound. Carrier horses had statistically significantly increased anterior chamber depth and decreased thickness of anterior uvea compared with noncarriers (P < 0.05). Uveal cysts had a wide range of location and ultrasonographic appearances. In 51/73 (69.86%) carrier horses, ultrasound detected ciliary cysts that were missed with direct ophthalmoscopy. CONCLUSIONS In this study, ultrasonography was useful to identify uveal cysts in PMEL17 mutant carriers and to assess anterior chamber depth.

High prevalence of molecular markers for resistance to chloroquine and pyrimethamine in Plasmodium falciparum from Zimbabwe

Chloroquine has been the first line drug of treatment for malaria in Zimbabwe until a recent adoption of an interim policy to treat using a combination of chloroquine (CQ) and sulfadoxine/pyrimethamine (SP). We examined the prevalence of parasites with mutations associated with resistance to the drug combination in three areas that have been previously described to differ in malaria endemicity. Our results show that the parasite population from the three areas had a high prevalence of molecular markers of resistance to chloroquine and pyrimethamine. The prevalence of crt (K76T) was 64, 82, and 92% for Chiredzi, Kariba, and Bindura, respectively. On the dhfr locus, the presence of triple mutations (codons 51, 59, and 108) was approximately 50% for all the three locations. On the other hand, the prevalence of dhps mutations (codons 436, 437, and 540) was low accounting for less than 20% in all the areas. Studies reported here demonstrate widespread prevalence of molecular markers associated with chloroquine and pyrimethamine resistance and should be taken into consideration for further refinement of malaria control strategies in Zimbabwe. The design and implementation of successful control strategies would benefit from understanding the prevalence of mutations associated with drug resistance in parasite populations.