Publications by authors named "Patricia Biedermann"

6 Publications

  • Page 1 of 1

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

Lancet Rheumatol 2020 Nov 21;2(11):e698-e711. Epub 2020 Aug 21.

Janssen Research and Development, Titusville, NJ, USA.

Background: Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis.

Methods: In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the value was less than 0·4.

Findings: The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12-2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22-3·95]), chest pain or angina (1·15 [1·05-1·26]), and heart failure (1·22 [1·02-1·45]).

Interpretation: Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit-risk trade-off when counselling those on hydroxychloroquine treatment.

Funding: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.
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http://dx.doi.org/10.1016/S2665-9913(20)30276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442425PMC
November 2020

Risk profiling of soil-transmitted helminth infection and estimated number of infected people in South Asia: A systematic review and Bayesian geostatistical Analysis.

PLoS Negl Trop Dis 2019 08 9;13(8):e0007580. Epub 2019 Aug 9.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: In South Asia, hundreds of millions of people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, and Trichuris trichiura). However, high-resolution risk profiles and the estimated number of people infected have yet to be determined. In turn, such information will assist control programs to identify priority areas for allocation of scarce resource for the control of soil-transmitted helminth infection.

Methodology: We pursued a systematic review to identify prevalence surveys pertaining to soil-transmitted helminth infections in four mainland countries (i.e., Bangladesh, India, Nepal, and Pakistan) of South Asia. PubMed and ISI Web of Science were searched from inception to April 25, 2019, without restriction of language, study design, and survey date. We utilized Bayesian geostatistical models to identify environmental and socioeconomic predictors, and to estimate infection risk at high spatial resolution across the study region.

Principal Findings: A total of 536, 490, and 410 georeferenced surveys were identified for A. lumbricoides, hookworm, and T. trichiura, respectively. We estimate that 361 million people (95% Bayesian credible interval (BCI) 331-395 million), approximately one-quarter of the South Asia population, was infected with at least one soil-transmitted helminth species in 2015. A. lumbricoides was the predominant species. Moderate to high prevalence (>20%) of any soil-transmitted helminth infection was predicted in the northeastern part and some northern areas of the study region, as well as the southern coastal areas of India. The annual treatment needs for the school-age population requiring preventive chemotherapy was estimated at 165 million doses (95% BCI: 146-185 million).

Conclusions/significance: Our risk maps provide an overview of the geographic distribution of soil-transmitted helminth infection in four mainland countries of South Asia and highlight the need for up-to-date surveys to accurately evaluate the disease burden in the region.
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http://dx.doi.org/10.1371/journal.pntd.0007580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709929PMC
August 2019

Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis.

Lancet Infect Dis 2015 Aug 21;15(8):927-40. Epub 2015 May 21.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, and University of Basel, Basel, Switzerland. Electronic address:

Background: Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries.

Methods: We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity.

Findings: The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18·5%, 17·6-19·5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52·8%, 95% CrI 48·7-57·8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population.

Interpretation: Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions.

Funding: European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation.
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http://dx.doi.org/10.1016/S1473-3099(15)00066-3DOI Listing
August 2015

Spatial and temporal distribution of soil-transmitted helminth infection in sub-Saharan Africa: a systematic review and geostatistical meta-analysis.

Lancet Infect Dis 2015 Jan 3;15(1):74-84. Epub 2014 Dec 3.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

Background: Interest is growing in predictive risk mapping for neglected tropical diseases (NTDs), particularly to scale up preventive chemotherapy, surveillance, and elimination efforts. Soil-transmitted helminths (hookworm, Ascaris lumbricoides, and Trichuris trichiura) are the most widespread NTDs, but broad geographical analyses are scarce. We aimed to predict the spatial and temporal distribution of soil-transmitted helminth infections, including the number of infected people and treatment needs, across sub-Saharan Africa.

Methods: We systematically searched PubMed, Web of Knowledge, and African Journal Online from inception to Dec 31, 2013, without language restrictions, to identify georeferenced surveys. We extracted data from household surveys on sources of drinking water, sanitation, and women's level of education. Bayesian geostatistical models were used to align the data in space and estimate risk of with hookworm, A lumbricoides, and T trichiura over a grid of roughly 1 million pixels at a spatial resolution of 5 × 5 km. We calculated anthelmintic treatment needs on the basis of WHO guidelines (treatment of all school-aged children once per year where prevalence in this population is 20-50% or twice per year if prevalence is greater than 50%).

Findings: We identified 459 relevant survey reports that referenced 6040 unique locations. We estimate that the prevalence of hookworm, A lumbricoides, and T trichiura among school-aged children from 2000 onwards was 16·5%, 6·6%, and 4·4%. These estimates are between 52% and 74% lower than those in surveys done before 2000, and have become similar to values for the entire communities. We estimated that 126 million doses of anthelmintic treatments are required per year.

Interpretation: Patterns of soil-transmitted helminth infection in sub-Saharan Africa have changed and the prevalence of infection has declined substantially in this millennium, probably due to socioeconomic development and large-scale deworming programmes. The global control strategy should be reassessed, with emphasis given also to adults to progress towards local elimination.

Funding: Swiss National Science Foundation and European Research Council.
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http://dx.doi.org/10.1016/S1473-3099(14)71004-7DOI Listing
January 2015

Geostatistical modelling of soil-transmitted helminth infection in Cambodia: do socioeconomic factors improve predictions?

Acta Trop 2015 Jan 6;141(Pt B):204-12. Epub 2014 Sep 6.

Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, PO Box, CH-4002 Basel, Switzerland; University of Basel, PO Box, CH-4003 Basel, Switzerland. Electronic address:

Soil-transmitted helminth infections are intimately connected with poverty. Yet, there is a paucity of using socioeconomic proxies in spatially explicit risk profiling. We compiled household-level socioeconomic data pertaining to sanitation, drinking-water, education and nutrition from readily available Demographic and Health Surveys, Multiple Indicator Cluster Surveys and World Health Surveys for Cambodia and aggregated the data at village level. We conducted a systematic review to identify parasitological surveys and made every effort possible to extract, georeference and upload the data in the open source Global Neglected Tropical Diseases database. Bayesian geostatistical models were employed to spatially align the village-aggregated socioeconomic predictors with the soil-transmitted helminth infection data. The risk of soil-transmitted helminth infection was predicted at a grid of 1×1km covering Cambodia. Additionally, two separate individual-level spatial analyses were carried out, for Takeo and Preah Vihear provinces, to assess and quantify the association between soil-transmitted helminth infection and socioeconomic indicators at an individual level. Overall, we obtained socioeconomic proxies from 1624 locations across the country. Surveys focussing on soil-transmitted helminth infections were extracted from 16 sources reporting data from 238 unique locations. We found that the risk of soil-transmitted helminth infection from 2000 onwards was considerably lower than in surveys conducted earlier. Population-adjusted prevalences for school-aged children from 2000 onwards were 28.7% for hookworm, 1.5% for Ascaris lumbricoides and 0.9% for Trichuris trichiura. Surprisingly, at the country-wide analyses, we did not find any significant association between soil-transmitted helminth infection and village-aggregated socioeconomic proxies. Based also on the individual-level analyses we conclude that socioeconomic proxies might not be good predictors at an aggregated large-scale analysis due to their large between- and within-village heterogeneity. Specific information of both the infection risk and potential predictors might be needed to obtain any existing association. The presented soil-transmitted helminth infection risk estimates for Cambodia can be used for guiding and evaluating control and elimination efforts.
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http://dx.doi.org/10.1016/j.actatropica.2014.09.001DOI Listing
January 2015