The EASEMENT study: A multicentre, observational, cross-sectional study to evaluate patient preferences, treatment satisfaction, quality of life, and healthcare resource use in patients with multiple myeloma receiving injectable-containing or fully oral therapies.

OBJECTIVE: As multiple myeloma (MM) therapies advance, understanding patients', caregivers', and physicians' perspectives on, and satisfaction with, available treatment options and their impact on quality of life (QoL), is important. METHODS: EASEMENT is a real-world, observational, cross-sectional study conducted in 19 sites within the UK, Canada, and Italy using retrospective chart reviews and surveys. Enrolled patients had clinical history available since diagnosis and had received ≥1 cycle of their current line of therapy. Primary objectives were to describe patient/caregiver QoL (EQ-5D-5L questionnaire), patient preference for oral/injectable therapies (single discrete-choice question), and patient satisfaction (TSQM-9 questionnaire). RESULTS: Between October 2018 and March 2020, 399 patients were enrolled (n = 192 newly diagnosed multiple myeloma [NDMM], n = 206 relapsed/refractory multiple myeloma [RRMM], n = 1 missing). Among NDMM and RRMM patients, 78%/22% and 42%/58% were receiving injectables/orals, respectively. Both NDMM and RRMM patients significantly preferred orals versus injectables (p < .0001). No significant differences were reported in treatment satisfaction or QoL, but treatment convenience favoured orals over injectables with near significance (p = .053). CONCLUSION: MM patients perceived greater convenience and preference for orals versus injectables. Oral treatments are useful for patients who cannot or prefer not to travel to clinics, or cannot perform self-injection within the community.

Standardizing registry data to the OMOP Common Data Model: experience from three pulmonary hypertension databases.

BACKGROUND: The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) can be used to transform observational health data to a common format. CDM transformation allows for analysis across disparate databases for the generation of new, real-word evidence, which is especially important in rare disease where data are limited. Pulmonary hypertension (PH) is a progressive, life-threatening disease, with rare subgroups such as pulmonary arterial hypertension (PAH), for which generating real-world evidence is challenging. Our objective is to document the process and outcomes of transforming registry data in PH to the OMOP CDM, and highlight challenges and our potential solutions. METHODS: Three observational studies were transformed from the Clinical Data Interchange Standards Consortium study data tabulation model (SDTM) to OMOP CDM format. OPUS was a prospective, multi-centre registry (2014-2020) and OrPHeUS was a retrospective, multi-centre chart review (2013-2017); both enrolled patients newly treated with macitentan in the US. EXPOSURE is a prospective, multi-centre cohort study (2017-ongoing) of patients newly treated with selexipag or any PAH-specific therapy in Europe and Canada. OMOP CDM version 5.3.1 with recent OMOP CDM vocabulary was used. Imputation rules were defined and applied for missing dates to avoid exclusion of data. Custom target concepts were introduced when existing concepts did not provide sufficient granularity. RESULTS: Of the 6622 patients in the three registry studies, records were mapped for 6457. Custom target concepts were introduced for PAH subgroups (by combining SNOMED concepts or creating custom concepts) and World Health Organization functional class. Per the OMOP CDM convention, records about the absence of an event, or the lack of information, were not mapped. Excluding these non-event records, 4% (OPUS), 2% (OrPHeUS) and 1% (EXPOSURE) of records were not mapped. CONCLUSIONS: SDTM data from three registries were transformed to the OMOP CDM with limited exclusion of data and deviation from the SDTM database content. Future researchers can apply our strategy and methods in different disease areas, with tailoring as necessary. Mapping registry data to the OMOP CDM facilitates more efficient collaborations between researchers and establishment of federated data networks, which is an unmet need in rare diseases.

Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study.

OBJECTIVES: Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. METHODS: We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 <40%. RESULTS: A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. CONCLUSION: HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. TRIAL REGISTRATION: Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.

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

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 I 2 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.

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

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.

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

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.

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

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.

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

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.