A general averaging method for count data with overdispersion and/or excess zeros in biomedicine.

With the aim of providing better estimation for count data with overdispersion and/or excess zeros, we develop a novel estimation method-optimal weighting based on cross-validation-for the zero-inflated negative binomial model, where the Poisson, negative binomial, and zero-inflated Poisson models are all included as its special cases. To facilitate the selection of the optimal weight vector, a K-fold cross-validation technique is adopted. Unlike the jackknife model averaging discussed in Hansen and Racine (2012), the proposed method deletes one group of observations rather than only one observation to enhance the computational efficiency. Furthermore, we also theoretically prove the asymptotic optimality of the newly developed optimal weighting based on cross-validation method. Simulation studies and three empirical applications indicate the superiority of the presented optimal weighting based on cross-validation method when compared with the three commonly used information-based model selection methods and their model averaging counterparts.

Forecasting models for leprosy cases: a scoping review protocol.

INTRODUCTION: Leprosy is a neglected tropical disease caused by Mycobacterium leprae that mainly affects the skin, the peripheral nerves, the mucosa of the upper respiratory tract and the eyes. Mathematical models and statistical methodologies could play an important role in decision-making and help maintain the gains in elimination programmes. Various models for predicting leprosy cases have been reported in the literature, but they have different settings and distinct approaches to predicting the cases. This study describes the protocol for a scoping review to identify and synthesise information from studies using models to forecast leprosy cases. METHODS AND ANALYSIS: A scoping review methodology will be applied following the Joanna Briggs Institute methodology for scoping reviews and will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews. We will perform a systematic search from when each database started until April 2022 and we will include the following electronic databases: MEDLINE via PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Science Literature Database. Data will be extracted and recorded on a calibrated predefined data form and will be presented in a tabular form accompanied by a descriptive summary. The Prediction Model Study Risk of Bias Assessment Tool (PROBAST) will be used. ETHICS AND DISSEMINATION: No ethical approval is required for this study. This scoping review will identify and map the methodological and other characteristics of modelling studies predicting leprosy cases. We hope that the review will contribute to scientific knowledge in this area and act as a basis for researchers designing and conducting leprosy models. This information can also be used to enhance national surveillance systems and to target specific policies. The protocol and consequent publications of this scoping review will be disseminated through peer-reviewed publications and policy briefs. SYSTEMATIC REVIEW REGISTRATION: This scoping review was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/W9375).

A comprehensive research agenda for zero leprosy.

BACKGROUND: Leprosy control achieved dramatic success in the 1980s-1990s with the implementation of short course multidrug therapy, which reduced the global prevalence of leprosy to less than 1 in 10 000 population. However, a period of relative stagnation in leprosy control followed this achievement, and only limited further declines in the global number of new cases reported have been achieved over the past decade. MAIN TEXT: In 2016, major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy, lowering the burden of disability and discrimination, and interrupting transmission. This led to the establishment of the Global Partnership for Zero Leprosy (GPZL) in 2018, with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building, resource mobilisation and an enabling research agenda. GPZL convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy. The result is a detailed research agenda focusing on diagnostics, mapping, digital technology and innovation, disability, epidemiological modelling and investment case, implementation research, stigma, post exposure prophylaxis and transmission, and vaccines. This research agenda is aligned with the research priorities identified by other stakeholders. CONCLUSIONS: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community. In a next step, research programmes must be developed, with individual components of the research agenda requiring distinct expertise, varying in resource needs, and operating over different timescales. Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process, from discovery to implementation.

The implementation of an integrated e-leprosy framework in a leprosy control program at primary health care centers in Indonesia.

BACKGROUND AND OBJECTIVE: The implementation of health information systems (HIS) could overcome obstacles in human resources and infrastructure at primary health care centers (PHCs). This study involved an e-Leprosy framework being integrated into the real setting of a leprosy control program in Indonesia. The objectives of this implementation study were to integrate e-Leprosy into a leprosy control program at 27 PHCs in Pekalongan District. Central Java Province, Indonesia to explore factors related the success or failure of such an implementation regarding the usability, involvement, and acceptance of e-Leprosy by PHC staff and to evaluate the effect of the implementation on leprosy patient attendance at PHCs. This paper is based on the Standards for Reporting Implementation Studies (StaRI) statement. METHOD: This study used mixed methods implementation research with longitudinal analysis and involved two groups of participants: Leprosy Surveillance Officers (LSOs), patients, and the relatives of patients. This study involved four phases consisting of preparation, baseline assessment, intervention, and evaluation. The qualitative study conducted focus group discussions and in-depth interviews. The e-Leprosy program automatically sent SMS reminders regarding leprosy treatment to the LSOs, patients, and patients' relatives every month. FINDINGS: This study determined that LSO had difficulties related to their workloads in PHCs while managing information and monitoring treatment and contact after release from treatment. The baseline assessment phase found that LSOs in Pekalongan District were unfamiliar with email but familiar using the internet. Overall, LSOs had a positive perception of the e-Leprosy program. The usability of this e-Leprosy program tended to increase over time, while acceptance of the e-Leprosy exhibited a significant relationship with computer and internet fluency (r = 0.48, p < 0.05) and age (r = 0.621, p < 0.01). The responsible patients correlated (r = 0.67, p < 0.01) with involvement in the e-Leprosy program. This study revealed that patient reminders increased on-time attendance by 13.9 % (p < 0.01 with OR = 2.41). CONCLUSION: Factors that should be considered during implementation HIS included the digital gap, PHC's staff workload, as well as the level of commitment and leadership in the health office.

Validation of a cross-NTD toolkit for assessment of NTD-related morbidity and disability. A cross-cultural qualitative validation of study instruments in Colombia.

BACKGROUND: Many neglected tropical diseases (NTDs) are not fatal, but they are disabling, disfiguring and stigmatizing. More accurate data on these aspects would benefit planning, monitoring and evaluation of interventions, as well as provision of appropriate services for the often life-long consequences. In 2015, a cross-NTD toolkit was developed, consisting of a variety of existing questionnaires to measure morbidity, disability and health-related quality of life. The toolkit covers the domains of the International Classification of Functioning, Disability and Health (ICF) framework. These tools have been developed in a source country, however, it was intended for the cross-NTD toolkit to be applicable across NTDs in many countries with different cultures and languages in order to generate universally comparative data. Therefore; the present study aimed to validate several tools of the toolkit among people affected by leprosy or leishmaniasis in the cultural settings of Cartagena and Cúcuta, Colombia. METHODOLOGY: This study aimed to validate the following tools among 55 participants between 18-85 years old, affected by leprosy and leishmaniasis: (I) Clinical Profile, (II) Self-Reporting Questionnaire (SRQ), (III) WHO Quality of Life assessment-abbreviated version (WHOQOL-BREF), and (IV) WHO Quality of Life assessment-Disability (WHOQOL-DIS). The tools were administered during face-to-face interviews and were followed by open questions about the respondents' thoughts on format of the tool and the understanding, relevance and acceptability of the items. The tools were validated using a qualitative method approach based on the framework for cultural equivalence, measured by the cultural, item, semantic and operational equivalences. RESULTS: The Clinical Profile was seen as acceptable and relevant, only the semantic equivalence was not as satisfying and needs a few adaptations. The SRQ was very well understood and shows to reach the equivalences for the population of Colombia without any additional changes. Several items of the WHOQOL-BREF and the WHOQOL-DIS were not well understood and changes are recommended due to semantic difficulties. Operational equivalence of both questionnaires was not as desired in relation to the used response scales. The participants shared that the tools are relevant and important for their particular situation. CONCLUSIONS/SIGNIFICANCE: The SRQ is found to be a valid tool for Colombia and can be included in the cross-NTD toolkit. The Clinical Profile, WHOQOL-BREF & WHOQOL-DIS need changes and retesting among Colombian people affected by an NTD. The toolkit as a whole is seen as useful to show the effects leprosy and leishmaniasis have on the participants. This cultural validation will contribute to a universally applicable cross-NTD toolkit.

Leprosy Post-Exposure Prophylaxis (LPEP) programme: study protocol for evaluating the feasibility and impact on case detection rates of contact tracing and single dose rifampicin.

INTRODUCTION: The reported number of new leprosy patients has barely changed in recent years. Thus, additional approaches or modifications to the current standard of passive case detection are needed to interrupt leprosy transmission. Large-scale clinical trials with single dose rifampicin (SDR) given as post-exposure prophylaxis (PEP) to contacts of newly diagnosed patients with leprosy have shown a 50-60% reduction of the risk of developing leprosy over the following 2 years. To accelerate the uptake of this evidence and introduction of PEP into national leprosy programmes, data on the effectiveness, impact and feasibility of contact tracing and PEP for leprosy are required. The leprosy post-exposure prophylaxis (LPEP) programme was designed to obtain those data. METHODS AND ANALYSIS: The LPEP programme evaluates feasibility, effectiveness and impact of PEP with SDR in pilot areas situated in several leprosy endemic countries: India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Complementary sites are located in Brazil and Cambodia. From 2015 to 2018, contact persons of patients with leprosy are traced, screened for symptoms and assessed for eligibility to receive SDR. The intervention is implemented by the national leprosy programmes, tailored to local conditions and capacities, and relying on available human and material resources. It is coordinated on the ground with the help of the in-country partners of the International Federation of Anti-Leprosy Associations (ILEP). A robust data collection and reporting system is established in the pilot areas with regular monitoring and quality control, contributing to the strengthening of the national surveillance systems to become more action-oriented. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant ethics committees in the countries. Results and lessons learnt from the LPEP programme will be published in peer-reviewed journals and should provide important evidence and guidance for national and global policymakers to strengthen current leprosy elimination strategies.

Weight bearing or non-weight bearing after surgically fixed ankle fractures, the WOW! Study: study protocol for a randomized controlled trial.

BACKGROUND: The optimal post-operative care regimen after surgically fixed Lauge Hansen supination exorotation injuries remains to be established. This study compares whether unprotected weight bearing as tolerated is superior to protected weight bearing and unprotected non-weight bearing in terms of functional outcome and safety. METHODS/DESIGN: The WOW! Study is a prospective multicenter clinical trial. Patients between 18 and 65 years of age with a Lauge Hansen supination exorotation type 2, 3 or 4 ankle fractures requiring surgical treatment are eligible for inclusion. An expert panel validates the classification and inclusion eligibility. After surgery, patients are randomized to either the 1) unprotected non-weight-bearing, 2) protected weight-bearing, or 3) unprotected weight-bearing group. The primary outcome measure is ankle-specific disability measured by the Olerud-Molander ankle score. Secondary outcomes are 1) quality of life (e.g., return to work and resumption of sport), 2) complications, 3) range of motion, 4) calf wasting, and 5) maximum pressure load after 3 months and 1 year. DISCUSSION: This trial is designed to compare the effectiveness and safety of unprotected weight bearing with two commonly used post-operative treatment regimens after internal fixation of specified, intrinsically stable but displaced ankle fractures. An expert panel has been established to evaluate every potential subject, which ensures that every patient is strictly screened according to the inclusion and exclusion criteria and that there is a clear indication for surgical fixation. TRIAL REGISTRATION: The WOW! Study is registered in the Dutch Trial Register ( NTR3727 ). Date of registration: 28-11-2012.

The pits and falls of graphical presentation.

Graphics are powerful tools to communicate research results and to gain information from data. However, researchers should be careful when deciding which data to plot and the type of graphic to use, as well as other details. The consequence of bad decisions in these features varies from making research results unclear to distortions of these results, through the creation of "chartjunk" with useless information. This paper is not another tutorial about "good graphics" and "bad graphics". Instead, it presents guidelines for graphic presentation of research results and some uncommon, but useful examples to communicate basic and complex data types, especially multivariate model results, which are commonly presented only by tables. By the end, there are no answers here, just ideas meant to inspire others on how to create their own graphics.

The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.

Effects of telemedicine in the treatment of patients with type 2 diabetes--a study protocol.

INTRODUCTION: Despite rehabilitation programmes offered to all patients with newly diagnosed type 2 diabetes in Denmark, a number of patients either never accomplish good diabetes regulation or the regulation deteriorates with time. Therefore, new approaches are needed. The aim of the present study is to examine whether telemedicine conferences with a nurse can contribute to achieving good diabetes control among patients with poorly regulated type 2 diabetes. MATERIAL AND METHODS: A total of 165 patients with type 2 diabetes who have formerly undergone a rehabilitation programme are randomized to either telemedicine intervention or usual care. The intervention lasts for 32 weeks and consists of monthly videoconferences with a nurse from a health-care centre as an add-on to usual care. Blood sugar, blood pressure and weight are regularly self-monitored and measurements are automatically transferred to a database. Glycaemic control (HbA1c level) is examined at baseline, 16 weeks, 32 weeks and 58 weeks (six months post intervention). Blood pressure, weight, waist/hip ratio, quality of life, physical activity, lipids, creatinine and haemoglobin are examined at baseline and after 32 weeks. CONCLUSION: The study will examine whether telemedicine technology can contribute to achieving good diabetes regulation. FUNDING: The City of Copenhagen and the Prevention Fund of the Capital Region of Denmark funded the project. Also "Smedemester Niels Hansen og Hustru Johanne F. Frederiksens Legat" has supported the study. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT01688778.

A conceptual protocol for translational research in the complex reality of leprosy.

In response to an international strategy to prioritise and focus research efforts in leprosy, this conceptual protocol outlines a research plan to address key translational research priorities. The protocol describes in broad terms a five-phase psychosocial and service-related research programme to facilitate: prevention of delay in diagnosis, improvement of adherence with multi-drug therapy, the roll out of chemoprophylaxis and increased participation in community based rehabilitation. The protocol proposes a model of research utilisation and the notion of complexity to form an integrating theoretical framework for exploring and enhancing research translation. The proposed sequential research programme is characterised by traditional and participatory strategies, culminating in participatory implementation of findings. Publication of the conceptual protocol prior to operationalisation and commencement of the research aims to encourage debate, refinement of strategies, collaboration and the optimisation of resources.

Comparing evaluation activities across multiple theories of practice.

This article compares and contrasts the evaluation activities described in Practical Participatory Evaluation (Cousins & Whitmore, 1998), Values-engaged Evaluation (Greene, 2005), and Emergent Realist Evaluation (Mark, Henry, & Julnes, 1998). Using the logic models developed to depict each of the three evaluation theories (Hansen, Alkin, & Wallace, 2013) as a starting point, both quantitative and qualitative analysis techniques are employed to discuss the similarities and differences across the practice prescriptions. The approaches are then described according to Miller's (2010) standards for empirical examinations of evaluation theory. Specifically, I offer speculation about their operational specificity and feasibility in practice. I argue that none of the models is completely specific, or wholly unique, and they all present challenges of adaptation into the field. However, the models each offer varying degrees of guidance and unique elements through their prescriptions.

When does a conceptual framework become a theory? Reflections from an accidental theorist.

In this short paper I reflect on the application of a program logic modeling approach to visualizing evaluation theory as it relates to practical participatory evaluation (PPE). The work of Hansen, Alkin and associates presented in this volume is well-thought out, carefully done, rigorous, and important. I found that their application of the approach resonated well with my understanding of PPE with a few notable exceptions. Specifically, the essence of the partnership aspect of the approach was underemphasized as was stakeholders' role in augmenting the credibility of evaluation findings and PPEs contribution to conceptual use. I then reminisce about the development and evolution of the participatory evaluation framework that we have been working with for so many years. I raise the point that we think of it as a theoretical framework to bound inquiry, not as an evaluation theory per se, which raises an interesting question: when does a theoretical framework become a theory?

Neglected tropical diseases: survey and geometry of randomised evidence.

OBJECTIVE: To assess the quantity and distribution of evidence from randomised controlled trials for the treatment of the major neglected tropical diseases and to identify gaps in the evidence with network analysis. DESIGN: Systematic review and network analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials and PubMed from inception to 31 August 2011. STUDY SELECTION: Randomised controlled trials that examined treatment of 16 neglected tropical diseases or complications thereof published in English, French, Spanish, Portuguese, German, or Dutch. RESULTS: We identified 971 eligible randomised trials. Leishmaniasis (184 trials, 23,039 participants) and geohelminth infections; 160 trials, 46,887 participants) were the most studied, while dracunculiasis (nine trials, 798 participants) and Buruli ulcer (five trials, 337 participants) were least studied. Relative to its global burden of disease, lymphatic filariasis had the fewest trials and participants. Only 11% of trials were industry funded. Either a single trial or trials with fewer than 100 participants comprised the randomised evidence for first or second line treatments for Buruli ulcer, human African trypanosomiasis, American trypanosomiasis, cysticercosis, rabies, echinococcosis, New World cutaneous leishmaniasis, and each of the foodborne trematode infections. Among the 10 disease categories with more than 40 trials, five lacked sufficient head to head comparisons between first or second line treatments. CONCLUSIONS: There is considerable variation in the amount of evidence from randomised controlled trials for each of the 16 major neglected tropical diseases. Even in diseases with substantial evidence, such as leishmaniasis and geohelminth infections, some recommended treatments have limited supporting data and lack head to head comparisons.

Evaluation of leprosy surveillance system in the Amazon region, Brazil, 2001-2007.

OBJECTIVES: We evaluated the leprosy surveillance system in the Amazon region, Brazil, 2001-2007, using evaluation guidelines from the US Centers for Disease Control and Prevention. RESULTS: We found that the leprosy surveillance system in the Amazon region is simple, presents good data quality and is representative in describing the sociodemographic profile and clinical classification of cases. The predictive value positive is high and its sensitivity is unknown. The grade two disability artificially increased in 2007 during the transition to a new version of the information system. The cases are reported, receive treatment and are discharged from the system as treatment completion in a timely fashion. Nevertheless, the dermatological and neurological examination introduces complexity to the system, which may account for the irregular data quality related to the evaluation of the disability degree, the system's lack of representativeness to describe mild neurological manifestations and low proportion of household contacts investigated. CONCLUSIONS: Despite its limitations, the leprosy surveillance system proved to be useful. Recommendations for its improvement were issued based on the results found. More data on surveillance systems in endemic countries are needed to facilitate valid comparisons between country indicators.

Evaluation of psychodynamic psychotherapy in a community mental health center.

This study describes an evaluation of the effectiveness of psychodynamic psychotherapy provided in an outpatient community mental health clinic. The study used a single group pretest-posttest design involving 78 clients. Clinical outcomes included overall psychosocial functioning and quality of life, level of subjective distress, interpersonal functioning and role functioning, measured by the Outcome Questionnaire (Lambert, Hansen, Umpress, Lunnen Okilshi, & Burlingame, 2000). Clients showed statistically significant improvement from pretest (first sessions) to completion of treatment in overall functioning, and quality of life, level of subjective distress, interpersonal functioning and role functioning. Eighty-five percent of clients made statistically and clinically significant change. Calculation of effect sizes for each outcome found moderate to strong change effects ranging from d = .4 to .9. The study illustrates a method of intervention research that therapists and agencies can use to integrate practical evaluation methods into their clinical services in order to improve mental health service to clients, to demonstrate the effectiveness of interventions, and to provide data to support coverage for needed services for clients.

Accuracy of references cited in articles published in Indian Journal of Dermatology, Venereology and Leprology: a pilot study.

BACKGROUND: Progress in science takes place when investigators build on the work of others. Therefore, in scientific communications, it is very important that others' work is correctly noted and understood. Cited references have been found to be inaccurate in every journal in which they have been examined. AIM: To analyze references cited in articles published in Indian Journal of Dermatology, Venereology and Leprology for their citation and quotation precision as an indicator of the quality of articles. METHODS: Twelve citation and five quotation errors were identified and defined. Fifty cited references were selected randomly from the May-June 2008 issue of the journal. For these citations, we obtained 44 full texts of papers and two abstracts. In one case, only citation errors could be verified from the Internet. Three citations of books could not be verified. Thus, citation errors were examined in 47 and quotation errors in 46 citations. RESULTS: Thirteen cited references (28.3%; 95% confidence interval [CI] 15.3-41.3%) were error-free. Twenty-eight citations (59.6%; 95% CI 45.5-73.6%) contained citation errors and 20 (43.5%; 95% CI 29.2-57.8%) quotation errors. CONCLUSION: RESULTS of this pilot study suggest that improving accuracy of the references is important. Solutions to this problem are suggested.