Publications by authors named "M Bresser"

9 Publications

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The coArtHA trial-identifying the most effective treatment strategies to control arterial hypertension in sub-Saharan Africa: study protocol for a randomized controlled trial.

Trials 2021 Jan 21;22(1):77. Epub 2021 Jan 21.

Ifakara Health Institute, Ifakara branch, Ifakara, United Republic of Tanzania.

Background: Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa.

Methods: In this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥ 18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90 mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤ 130/80 mmHg and ≤ 140/90 mmHg among those aged < 65 years and ≥ 65 years, respectively. Clinical manifestations of end-organ damage and cost-effectiveness at 6 months are secondary endpoints.

Discussion: This trial will help to identify the most effective and cost-effective treatment strategies for uncomplicated arterial hypertension among people of African descent living in rural sub-Saharan Africa and inform future clinical guidelines on antihypertensive management in the region.

Trial Registration: Clinicaltrials.gov NCT04129840 . Registered on 17 October 2019 ( https://www.clinicaltrials.gov/ ).
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http://dx.doi.org/10.1186/s13063-021-05023-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818218PMC
January 2021

Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania.

BMC Infect Dis 2020 Oct 19;20(1):773. Epub 2020 Oct 19.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART).

Methods: GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up.

Discussion: This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART.

Trial Registration: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .
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http://dx.doi.org/10.1186/s12879-020-05491-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574572PMC
October 2020

Home-based oral self-testing for absent and declining individuals during a door-to-door HIV testing campaign in rural Lesotho (HOSENG): a cluster-randomised trial.

Lancet HIV 2020 11 9;7(11):e752-e761. Epub 2020 Oct 9.

Clinical Research Unit, Department of Medicine, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.

Background: In sub-Saharan Africa, home-based HIV testing is validated and accepted, but coverage is low because household members are often absent during home-based testing campaigns. We aimed to measure the effect of a secondary distribution of oral-fluid HIV self-tests on coverage during home-based testing in rural Lesotho.

Methods: The Home-Based Self-Testing (HOSENG) trial was a cluster-randomised, non-blinded superiority trial in rural villages in the catchment area of 20 health facilities of two districts in Lesotho (Butha-Buthe and Mokhotlong). Eligible villages had a consenting village chief and at least one registered village health worker; eligible households had a consenting representative aged 18 years or older. The HOSENG trial provided a recruitment platform for the interlinked Village-Based Refill of Antiretroviral Therapy (VIBRA) trial. Villages were randomly assigned 1:1:1:1 with block sizes of four to one of four groups: VIBRA control and HOSENG control; VIBRA control and HOSENG intervention; VIBRA intervention and HOSENG control; and VIBRA intervention and HOSENG intervention. Randomisation was stratified by district, village size, and access to the nearest health facility. An independent statistician was responsible for the computer-generated randomisation list. In the intervention group, oral-fluid HIV self-tests were left for absent or declining household members (aged ≥12 years) during a home visit from the HIV testing campaign team. One present household member was trained on self-test use. Distributed self-tests were followed up by village health workers. In control village clusters, absent or declining household members were referred to the clinic for HIV testing. The primary outcome was HIV testing coverage among all household members aged 12 years or older within 120 days, defined as a confirmed HIV test result or known status, reported in testing registers at the health facilities or on the follow-up forms of the village health worker. Adjusted random-effects logistic regression with individuals as the unit of analysis was used. This trial is registered with ClinicalTrials.gov, NCT03598686.

Findings: Between July 26, 2018, and Dec 12, 2018, 3091 consenting households with 7816 household members aged 12 years or older were enrolled and randomly assigned (intervention: 57 village clusters, 1620 households, 4174 household members; control: 49 village clusters, 1471 households, 3642 household members). In the control group, 38 (3%) of 1455 initially absent or declining household members tested at a clinic within 120 days. In the intervention group, 841 (53%) of 1601 initially absent or declining household members had a confirmed status within 120 days; 12 (1%) of 841 tested at the clinic and 829 (99%) used their self-test kit. This resulted in a testing coverage of 2201 (60%) of 3642 in the control group versus 3386 (81%) of 4174 in the intervention group (odds ratio 3·00 [95% CI 2·52-3·59]; p<0·0001).

Interpretation: Secondary distribution of oral-fluid HIV self-tests during home-based testing increases testing coverage substantially and thus presents a promising add-on during testing campaigns.

Funding: Swiss National Science Foundation.
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http://dx.doi.org/10.1016/S2352-3018(20)30233-2DOI Listing
November 2020

Fractional Flow Reserve Derived from Computed Tomography Coronary Angiography in the Assessment and Management of Stable Chest Pain: Rationale and Design of the FORECAST Trial.

Cardiovasc Revasc Med 2020 07 9;21(7):890-896. Epub 2019 Dec 9.

Faculty of Medicine, University of Southampton, UK; Coronary Research Group, University Hospital Southampton, Southampton, UK. Electronic address:

Background: Fractional flow reserve measurement based on computed tomography (FFR) is a novel, well validated, non-invasive method for determining the presence and extent of coronary artery disease (CAD) combined with a physiological assessment of vessel-specific ischemia in patients with chest pain. Previous studies indicate that FFR reduces the uptake of invasive angiography that shows no significant CAD, without compromising patient safety. The clinical effectiveness and economic impact of using FFR instead of other tests in the initial evaluation of patients with stable chest pain has not been tested in a randomized trial.

Methods: The FORECAST trial will randomise 1400 patients with stable chest pain to receive either FFR or routine clinical assessment as directed by the National Institute for Health and Care Excellence (NICE) CG95 guideline for Chest Pain of Recent Onset. The primary endpoint will be resource utilisation over the subsequent nine months, including non-invasive cardiac investigations, invasive coronary angiography, coronary revascularization, hospitalization for cardiac events, and the use of cardiac medications. Key pre-specified secondary endpoints will be major adverse cardiac events, angina severity, quality of life, patient satisfaction, time to definitive management plan, time to completion of initial evaluation, number of hospital attendances, and working days lost in patients who are in employment.

Conclusion: The FORECAST randomized trial will assess the clinical and economic outcomes of using FFR as the primary test to evaluate patients presenting with stable chest pain.
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http://dx.doi.org/10.1016/j.carrev.2019.12.009DOI Listing
July 2020

VIBRA trial - Effect of village-based refill of ART following home-based same-day ART initiation vs clinic-based ART refill on viral suppression among individuals living with HIV: protocol of a cluster-randomized clinical trial in rural Lesotho.

Trials 2019 Aug 22;20(1):522. Epub 2019 Aug 22.

Clinical Research Unit, Department of Medicine, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051, Basel, Switzerland.

Background: There is a need for evaluating community-based antiretroviral therapy (ART) delivery models to improve overall performance of HIV programs, specifically in populations that may have difficulties to access continuous care. This cluster-randomized clinical trial aims to evaluate the effectiveness of a multicomponent differentiated ART delivery model (VIBRA model) after home-based same-day ART initiation in remote villages in Lesotho, southern Africa.

Methods/design: The VIBRA trial (VIllage-Based Refill of ART) is a cluster-randomized parallel-group superiority clinical trial conducted in two districts in Lesotho, southern Africa. Clusters (i.e., villages) are randomly assigned to either the VIBRA model or standard care. The clusters are stratified by district, village size, and village access to the nearest health facility. Eligible individuals (HIV-positive, aged 10 years or older, and not taking ART) identified during community-based HIV testing campaigns are offered same-day home-based ART initiation. The intervention clusters offer a differentiated ART delivery package with two features: (1) drug refills and follow-ups by trained and supervised village health workers (VHWs) and (2) the option of receiving individually tailored adherence reminders and notifications of viral load results via SMS. The control clusters will continue to receive standard care, i.e., collecting ART refills from a clinic and no SMS notifications. The primary endpoint is viral suppression 12 months after enrolment. Secondary endpoints include linkage to and engagement in care. Furthermore, safety and cost-effectiveness analyses plus qualitative research are planned. The minimum target sample size is 262 participants. The statistical analyses will follow the CONSORT guidelines. The VIBRA trial is linked to another trial, the HOSENG (HOme-based SElf-testiNG) trial, both of which are within the GET ON (GETing tOwards Ninety) research project.

Discussion: The VIBRA trial is among the first to evaluate the delivery of ART by VHWs immediately after ART initiation. It assesses the entire HIV care cascade from testing to viral suppression. As most countries in sub-Saharan Africa have cadres like the VHW program in Lesotho, this model-if shown to be effective-has the potential to be scaled up. The system impact evaluation will provide valuable cost estimations, and the qualitative research will suggest how the model could be further modified to optimize its impact.

Trial Registration: Clinicaltrials.gov, NCT03630549 . Registered on 15 August 2018.
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http://dx.doi.org/10.1186/s13063-019-3510-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704675PMC
August 2019

The HOSENG trial - Effect of the provision of oral self-testing for absent and refusing individuals during a door-to-door HIV-testing campaign on testing coverage: protocol of a cluster-randomized clinical trial in rural Lesotho.

Trials 2019 Aug 13;20(1):496. Epub 2019 Aug 13.

Clinical Research Unit, Department of Medicine, Swiss Tropical and Public Health Institute, Socinstrasse 57, 4051, Basel, Switzerland.

Background: HIV-testing coverage remains below the targeted 90% despite efforts and resources invested. Home-based HIV-testing is a key approach endorsed by the World Health Organization (WHO), especially to reach individuals who might not seek testing otherwise. Although acceptance of testing during such campaigns is high, coverage remains low due to absent household members. This cluster-randomized trial aims to assess increase in testing coverage using oral HIV self-testing (HIVST) among individuals who are absent or decline testing during home-based HIV-testing.

Methods: The HOSENG (HOme-based SElf-testiNG) trial is a cluster-randomized, parallel-group, superiority trial in two districts of Lesotho, Southern Africa. Clusters are stratified by district, village size, and village access to the nearest health facility. Cluster eligibility criteria include: village is in catchment area of one of the study facilities, village authority provides consent, and village has a registered, capable, and consenting village health worker (VHW). In intervention clusters, HIV self-tests are provided for eligible household members who are absent or decline HIV-testing in the presence of the campaign team. In control clusters, standard of care for absent and refusing individuals applies, i.e., referral to a health facility. The primary outcome is HIV-testing coverage among individuals aged 12 years or older within 120 days after enrollment. Secondary objectives include HIV-testing coverage among other age groups, and uptake of the different testing modalities. Statistical analyses will be conducted and reported in line with CONSORT guidelines. The HOSENG trial is linked to the VIBRA (Village-Based Refill of ART) trial. Together, they constitute the GET ON (GETting tOwards Ninety) research project.

Discussion: The HOSENG trial tests whether oral HIVST may be an add-on during door-to-door testing campaigns towards achieving optimal testing coverage. The provision of oral self-test kits, followed up by VHWs, requires little additional human resources, finances and logistics. If cost-effective, this approach should inform home-based HIV-testing policies not only in Lesotho, but in similar high-prevalence settings.

Trial Registration: ClinicalTrials.gov, (ID: NCT03598686 ). Registered on 25 July 2018. More information is available at www.getonproject.wordpress.com .
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http://dx.doi.org/10.1186/s13063-019-3469-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693145PMC
August 2019

An ERP study on L2 syntax processing: When do learners fail?

Front Psychol 2014 25;5:1072. Epub 2014 Sep 25.

Center for Language and Cognition, University of Groningen Groningen, Netherlands ; Department of Language and Linguistics, University of Essex Colchester, UK.

Event-related brain potentials (ERPs) can reveal online processing differences between native speakers and second language (L2) learners during language comprehension. Using the P600 as a measure of native-likeness, we investigated processing of grammatical gender agreement in highly proficient immersed Romance L2 learners of Dutch. We demonstrate that these late learners consistently fail to show native-like sensitivity to gender violations. This appears to be due to a combination of differences from the gender marking in their L1 and the relatively opaque Dutch gender system. We find that L2 use predicts the effect magnitude of non-finite verb violations, a relatively regular and transparent construction, but not that of gender agreement violations. There were no effects of age of acquisition, length of residence, proficiency or offline gender knowledge. Additionally, a within-subject comparison of stimulus modalities (written vs. auditory) shows that immersed learners may show some of the effects only in the auditory modality; in non-finite verb violations, an early native-like N400 was only present for auditory stimuli. However, modality failed to influence the response to gender. Taken together, the results confirm the persistent problems of Romance learners of Dutch with online gender processing and show that they cannot be overcome by reducing task demands related to the modality of stimulus presentation.
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http://dx.doi.org/10.3389/fpsyg.2014.01072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4174886PMC
October 2014

Creatine kinase isoform analysis in the detection and assessment of thrombolysis in man.

Circulation 1987 Jun;75(6):1162-9

Recent demonstrations of the efficacy of intravenous thrombolytic therapy in acute myocardial infarction have emphasized the need for a noninvasive index of successful reperfusion. The tissue form of MM creatine kinase (MM3) is known to undergo posttranslational conversion to modified forms MM2 and MM1 after release into the plasma following acute infarction. Since this conversion is rapid, sustained elevation of plasma MM3 may be a marker of the prolonged creatine kinase release characteristic of nonreperfused infarction. Therefore, we investigated the rate of decline of plasma MM3 in a consecutive series of patients undergoing thrombolytic therapy of acute myocardial infarction, all of whom underwent acute angiography to assess treatment success, as well as in 30 conventionally treated patients. Among 55 patients with angiographically documented successful reperfusion (group IA), the rate of decline of MM3 was 4.18 +/- 1.25%/hr (mean +/- SD); in contrast, the rate of decline was 2.37 +/- 1.11%/hr in 39 patients with angiographically documented unsuccessful reperfusion (group IB) and 1.77 +/- 1.46%/hr among the 30 patients receiving conventional treatment (group II) (p less than .001 for groups IB and II vs group IA). A cutoff value of 3.1%/hr minimized the overlap between the groups; 48/55 (87%) patients with successful reperfusion had a rate of decline of MM3 of 3.1%/hr or more, while 29 of 39 (74%) patients in whom thrombolysis was unsuccessful and 27 of 30 (90%) patients receiving conventional treatment had a rate of decline less than 3.1%/hr (p less than .001 for groups IB and II vs group IA).(ABSTRACT TRUNCATED AT 250 WORDS)
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http://dx.doi.org/10.1161/01.cir.75.6.1162DOI Listing
June 1987

Bifunctionality and polarized infidelity at the hisB locus of Aspergillus nidulans.

Mol Gen Genet 1984 ;193(2):332-9

The histidine (hisB) locus of Aspergillus nidulans is unusual in two ways. Firstly, it is bifunctional; besides coding for imidazole glycerol phosphate (IGP) dehydrase, it is required for the production of ascospores (fertility). It appears, therefore, to be partly homologous to the hisB locus of Salmonella typhimurium, which codes for IGP dehydrase and histidinol phosphate phosphatase. Secondly, during meiosis it is often inaccurately transmitted to the progeny (infidelity). This phenomenon may be akin to the aberrant recombination events which cause Bar reversion in Drosophila, "selfing" in Salmonella and Neurospora, and gene fusions of the haemoglobin lepore type. A molecular model is proposed to account for the results.
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http://dx.doi.org/10.1007/BF00330690DOI Listing
March 1984