The spectrum of central nervous system manifestations in leprosy: a systematic review of published case reports and case series.

BACKGROUND: This systematic review aimed to investigate central nervous system (CNS) involvement in leprosy by analysing multiple cohort studies, individual cases and case series. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. PubMed, Scopus and Embase databases were searched up to 8 July 2023, using a predefined search strategy. Inclusion criteria included patients diagnosed with leprosy with evidence of CNS involvement. The quality of the included cases was evaluated using the Joanna Briggs Institute checklist. RESULTS: A total of 34 records were identified, including 18 cohort studies and 16 reports describing 27 isolated cases. Autopsies revealed macroscopic changes in the spinal cord, neurofibrillary tangles and senile plaques. Mycobacterium leprae was detected in neurons of the medulla oblongata and spinal cord using PCR and phenolic glycolipid 1 staining. Cerebrospinal fluid (CSF) analysis showed inflammatory changes, increased gamma globulins and detection of Mycobacterium leprae antigens and antibodies. In 21 patients (78%), spinal cord/brachial plexus abnormities were detected. In the majority, MRI revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity in the cervical cord. In patients with brainstem involvement, T2/FLAIR hyperintensity was noted in the cerebellar peduncles, facial nerve nuclei and/or other cranial nerve nuclei. Brain parenchymal involvement was noted in three patients. CONCLUSIONS: This systematic review provides evidence of CNS involvement in leprosy, based on autopsy findings, neuroimaging, CSF analysis and neurophysiological studies.

Assessment of Clinical, Histopathological, and Bacteriological Findings in Treated Leprosy Patients with Persistent Skin Lesions: A Retrospective Cohort Study.

Since the introduction of multidrug therapy (MDT), various disabilities/morbidities due to leprosy have been prevented. However, there is a subset of patients in whom the skin lesions do not resolve completely or remain unchanged despite a full course of MDT, which is a great source of anxiety to the patient and their family members. Hence, we tried to ascertain the putative causes and risk factors of persistent skin lesions (PSLs) by analyzing the clinical, histopathological, bacteriological, and drug resistance patterns. This is a retrospective, cohort study wherein 35 patients who had PSLs after completion of MDT were included. The majority of the patients were 18 to 30 years of age, with males predominating. Borderline tuberculoid leprosy was the most common clinical spectrum observed (71.4%). The majority had PSLs distributed predominantly over photo-exposed sites (upper limbs > trunk > face). Eight patients (22.8%) had a history of contact with leprosy patients in their family, and six patients (17.1%) had associated comorbidities. Improvement in histopathological parameters such as a decrease in granuloma fraction was observed in 22 patients (62.8%) with PSLs after release from treatment in comparison with baseline. Four patients (11.4%) were noted to have drug resistance (three to rifampicin and one to dapsone). Thus, our study emphasizes that leprosy patients with PSLs after completion of MDT should undergo histopathological evaluation and drug resistance studies.

Prevalence and Predictors of COVID-19 Long-Term Symptoms: A Cohort Study from the Amazon Basin.

It remains unclear whether a previous history of tropical infectious diseases and a second SARS-COV-2 infection may influence the likelihood of later symptoms. In this prospective cohort study, individuals infected with SARS-CoV-2 were followed up by telephone shortly after diagnosis of COVID-19 and again 12 months later. Poisson regression was used to identify the predictors of the highest number of symptoms in the post-COVID-19 syndrome. A total of 1,371 patients with COVID-19, with a mean age of 39.7 ± 11.7 years and 50% female, were followed for 12 months. Reinfection was found in 32 (2.3%) participants, and 806 (58.8%) individuals reported a previous history of dengue, malaria, Zika, chikungunya, leprosy, and visceral leishmaniasis. Eight hundred seventy-seven (63.9%) participants reported late symptoms related to COVID-19. After adjusting for multiple factors, female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection were independent predictors of higher number of symptoms in post-COVID-19 syndrome. Female sex, non-White race, number of acute-phase symptoms, body mass index, and reinfection, but not previous endemic tropical diseases, were associated with long-term symptoms.

Risk of skin cancer in kidney, liver and heart recipients: A nationwide population-based study in Taiwan.

Background Previous population-based studies in western countries had revealed increased skin cancer risk among transplant recipients compared to the general population. However, population-based studies in Asia on skin cancer among recipients of different transplanted organs were lacking in the literature. Aims This study aims to estimate skin cancer risk among recipients in Taiwan, examine the association between each specific type of skin cancer and each type of transplanted organ, and compare skin cancer risk between different immunosuppressive regimens. Methods This population-based retrospective cohort study identified 7550 patients with heart, lung, kidney or liver transplantation and 30,200 controls matched for gender, age and comorbidity index from the National Health Insurance Research Database in Taiwan between 2000 and 2015. Using multivariable Cox proportional hazard models, we estimated the hazard ratios and 95% confidence intervals for the correlation of skin cancer with organ transplantation as well as immunosuppressive regimen. Results Organ transplant recipients in Taiwan had an increased risk of skin cancer with adjusted hazard ratios of 4.327 (95% confidence intervals 2.740-6.837, P < 0.001), with the greatest risk, observed among heart recipients (adjusted hazard ratios 6.348, 95% confidence intervals 3.080-13.088, P < 0.001). The risk of non-melanoma skin cancer and melanoma was 4.473 (95% confidence intervals 2.568-7.783, P < 0.001) and 3.324 (95% confidence intervals 1.300-8.172, P < 0.001), respectively. When comparing immunosuppressants, those with calcineurin inhibitors carried the highest risk of skin cancer (adjusted hazard ratios 4.789, 95% confidence intervals 3.033-7.569, P < 0.001), followed by those with antimetabolites (adjusted hazard ratios 4.771, 95% confidence intervals 3.025-7.541, P < 0.001). Limitations We could not evaluate confounding behavioural risk factors of skin cancers that were not documented in the database, nor could we recognize patients' compliance with immunosuppressants. Conclusion Organ recipients have a greater risk of skin cancer. Clinicians should inform recipients of the importance of photoprotection and regular dermatologic follow-up.

Moderna COVID-19 vaccine was linked to myocarditis or myopericarditis at 28 d (4.2 events/100 000 persons).

SOURCE CITATION: Husby A, Hansen JV, Fosbøl E, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ. 2021;375:e068665. 34916207.

Assessing the causal effects of long-term exposure to PM2.5 during pregnancy on cognitive function in the adolescence: Evidence from a nationwide cohort in China.

The effects of air pollution on adolescents need further consideration. Although there is evidence that maternal exposure to air pollution may affect the cognitive function of offspring, relevant studies remain limited and inconsistent, with a lack of studies assessing the causal effects and evidence from developing countries. Using data from Chinese Family Panel Studies, a representative Chinese nationwide cohort study, OLS combined with instrumental variable + two-stage least square (IV+2SLS) was used to explore the causal effects of exposure to PM2.5 concentrations during pregnancy on the cognitive function of offspring when they become adolescents. After detailed argumentation and multiple testing, Planetary Boundary Layer Height (PBLH) and Surface Pressure (SP) were selected as the instrumental variables for this study. One thousand five hundred fifty-five adolescents participated in this study, with a mean age of 13.3 years (sd = 2.3). There were 706 females (45.4%), the mean maternal PM2.5 exposure concentration was 64.9 µg/m3, and recorded a mean cognitive function score of 38.1 (sd = 9.4). The OLS results found that maternal exposure to air pollution increased cognitive function in offspring adolescents, corroborating the presence of endogeneity. Multi-domain knowledge, the results of the weak instrumental variable assessments of F-tests (F = 237 > 10) and Stock-yogo tests (minimum eigenvalue statistic = 153.16 > 16.38), and the results of the Hansen J overidentification test (p > 0.05) verified the plausibility and validity of the instrumental variables. The IV+2SLS results, following causal modeling, showed that PM2.5 exposure during pregnancy impairs the cognitive ability of offspring adolescents (ß = -0.040, p < 0.05). Robustness tests also validated the results. This study provides important policy implications for developing countries on protecting their adolescents and reminds parents that the protection of adolescents from air pollution should begin from conception.

A simple assay to quantify mycobacterial lipid antigen-specific T cell receptors in human tissues and blood.

T cell receptors (TCRs) encode the history of antigenic challenge within an individual and have the potential to serve as molecular markers of infection. In addition to peptide antigens bound to highly polymorphic MHC molecules, T cells have also evolved to recognize bacterial lipids when bound to non-polymorphic CD1 molecules. One such subset, germline-encoded, mycolyl lipid-reactive (GEM) T cells, recognizes mycobacterial cell wall lipids and expresses a conserved TCR-ɑ chain that is shared among genetically unrelated individuals. We developed a quantitative PCR assay to determine expression of the GEM TCR-ɑ nucleotide sequence in human tissues and blood. This assay was validated on plasmids and T cell lines. We tested blood samples from South African subjects with or without tuberculin reactivity or with active tuberculosis disease. We were able to detect GEM TCR-ɑ above the limit of detection in 92% of donors but found no difference in GEM TCR-ɑ expression among the three groups after normalizing for total TCR-ɑ expression. In a cohort of leprosy patients from Nepal, we successfully detected GEM TCR-ɑ in 100% of skin biopsies with histologically confirmed tuberculoid and lepromatous leprosy. Thus, GEM T cells constitute part of the T cell repertoire in the skin. However, GEM TCR-ɑ expression was not different between leprosy patients and control subjects after normalization. Further, these results reveal the feasibility of developing a simple, field deployable molecular diagnostic based on mycobacterial lipid antigen-specific TCR sequences that are readily detectable in human tissues and blood independent of genetic background.

[Factors associated with timing of lepra reactions in a cohort from 2008 to 2016 in Rondônia, Amazon Region, Brazil]. / Fatores associados ao tempo de ocorrência das reações hansênicas numa coorte de 2008 a 2016 em Rondônia, Região Amazônica, Brasil.

The clinical management of leprosy patients poses a specific challenge, namely lepra reactions. This non-concurrent cohort study aimed to analyze the timing of the first lepra reaction during and after polychemotherapy (PCT) and associated factors. A total of 1,621 patients were assessed (PB = 8.9% and MB = 91.1%) from 2008 to 2016, reported to the System of Reaction States in Leprosy (SisReação/RO) database. Reactions occurred predominantly during PCT (997; 61.5%) and less frequently only after PCT (624; 38.5%). Earliness of the reaction after diagnosis was analyzed with Kaplan-Meier survival curves, with comparison between the PB and MB groups using the Mantel-Cox log-rank test. Univariate and multivariate Cox regression models were constructed to identify factors associated with occurrence of lepra reactions (hazard ratio) and the corresponding 95%CI. The multivariate model included variables with p-values < 0.20 in the univariate analysis. PB patients developed reactions earlier than MB patients. Other characteristics were associated with earlier reactions: female gender and negative smear microscopy. In the aggregate period (during and after PCT), PB presented 24% higher risk of lepra reaction than MB patients, and negative smear microscopy increased this risk by 40% compared to positive smear microscopy. During and after PCT, PB presented 1.3 and 1.6 times the risk, respectively, of reactions when compared to MB patients. We thus recommend prioritizing surveillance of lepra reactions during and after PCT as measures to prevent physical disabilities and to improve quality of life for persons with leprosy.

O manejo clínico de pacientes com hanseníase apresenta um desafio particular que são as reações. O objetivo deste estudo de coorte não concorrente foi analisar o tempo e fatores associados à ocorrência da primeira reação durante e após o tratamento da poliquimioterapia (PQT). Avaliou-se 1.621 pacientes paucibacilares (PB = 8,9%) e multibacilares (MB = 91,1%) de 2008 a 2016 notificados no Sistema de Estados Reacionais em Hanseníase/Rondônia (SisReação/RO). Prevaleceu a ocorrência durante o tratamento da PQT = 997 (61,5%), e 624 (38,5%) somente após o PQT. A precocidade da reação, a partir do diagnóstico, foi analisada por meio de curvas de sobrevida de Kaplan-Meier e comparadas entre os grupos PB e MB, usando o teste de log-rank de Mantel-Cox; e foram construídos modelos de regressão de Cox univariada e multivariada para identificar os fatores associados à ocorrência da reação (hazard ratio) e os correspondentes IC95%. No modelo multivariado foram incluídas variáveis com valores de p < 0,2 na análise univariada. Os PB desenvolveram reação de forma mais precoce do que os MB. Outras características associaram-se à reação em menor tempo: sexo feminino e baciloscopia negativa. No período agregado (durante e após a PQT), os pacientes PB apresentaram risco 24% maior de reação do que os MB e aqueles com baciloscopia negativa aumentaram este risco em 40% comparado à baciloscopia positiva. Durante e após a PQT, os PB apresentaram 1,3 e 1,6 vezes maior risco de ocorrência da reação dos pacientes MB. Dessa forma, recomendamos priorizar ações de vigilância para reações hansênicas durante e após a PQT como medidas de prevenção de incapacidades físicas e de melhoria na qualidade de vida das pessoas acometidas pela hanseníase.

La gestión clínica de pacientes con hanseniasis presenta un desafío particular que son las reacciones. El objetivo de este estudio de cohorte no concurrente fue analizar el tiempo y factores asociados a la ocurrencia de la primera reacción durante y tras el tratamiento de la poliquimioterapia (PQT). Se evaluó a 1621 pacientes (PB = 8,9% y MB = 91,1%) de 2008 a 2016, notificados en el Sistema de Estados Reaccionarios en Lepra (SisReação/RO). Prevaleció la ocurrencia durante la PQT = 997 (61,5%), y 624 (38,5%) solamente tras la PQT. La precocidad de la reacción a partir del diagnóstico se analizó mediante curvas de supervivencia de Kaplan-Meier y se compararon entre los grupos PB y MB, usando el test de log-rank de Mantel-Cox; asimismo, se construyeron modelos de regresión univariada y multivariada de Cox para identificar los factores asociados con la ocurrencia de la reacción (cociente de riesgos) y los correspondientes IC95%. En el modelo multivariado se incluyeron las variables con valores de p < 0,2 en el análisis univariado. Los PB desarrollaron una reacción de forma más precoz que los MB. Otras características se asociaron a la reacción en menor tiempo: sexo femenino y baciloscopia negativa. En el período agregado (durante y tras PQT), los PB presentaron un riesgo un 24% mayor de reacción que los multibacilares y la baciloscopia negativa aumentó este riesgo en un 40%, comparado con la baciloscopia positiva. Durante y tras el tratamiento PQT, los PB presentaron 1,3 y 1,6 veces el riesgo de ocurrencia de la reacción de los pacientes MB. De esa forma, recomendamos priorizar acciones de vigilancia para reacciones hansénicas durante y tras PQT, como medidas de prevención de discapacidades físicas, así como de mejoría en la calidad de vida de personas afectadas por la hanseniasis.

Low risk of relapse and deformity among leprosy patients who completed multi-drug therapy regimen from 2005 to 2010: A cohort study from four districts in South India.

INTRODUCTION: Relapse of leprosy among patients released from treatment (RFT) is an indicator of the success of anti-leprosy treatment. Due to inadequate follow-up, relapse in leprosy patients after RFT is not systematically documented in India. Relapsed leprosy patients pose a risk in the transmission of leprosy bacilli. We determined the incidence of relapse and deformity among the patients RFT from the leprosy control programme in four districts in South India. METHODS: We conducted two follow-up surveys in 2012 and 2014 among the leprosy patients RFT between 2005 and 2010. We assessed them for any symptoms or signs of relapse, persistence and deformity. We collected slit skin samples (SSS) for smear examination. We calculated overall incidence of relapse and deformity per 1000 person-years (PY) with 95% confidence intervals (CI) and cumulative risk of relapse. RESULTS: Overall, we identified 69 relapse events, 58 and 11, during the first and second follow-up surveys, respectively. The incidence of relapse was 5.42 per 1000 PY, which declined over the years after RFT. The cumulative risk of relapse was 2.24%. The rate of deformity among the relapsed patients was 30.9%. The overall incidence of deformity was 1.65 per 1000 person years. The duration of M. leprae detection in smears ranged between 2.38 and 7.67 years. CONCLUSIONS: Low relapse and deformity rates in leprosy RFT patients are indicative of treatment effectiveness. However, a higher proportion of detection of deformity among relapsed cases is a cause for concern. Periodic follow-up of RFT patients for up to 3 years to detect relapses early and ensure appropriate treatment will minimize the development of deformity among relapsed patients.

Assisted reproductive technology treatment and risk of breast cancer: a population-based cohort study.

STUDY QUESTION: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation? SUMMARY ANSWER: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years. WHAT IS KNOWN ALREADY: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment. STUDY DESIGN, SIZE, DURATION: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08). LIMITATIONS, REASONS FOR CAUTION: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation. WIDER IMPLICATIONS OF THE FINDINGS: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Quality of life in children with atopic dermatitis: A one-year prospective cohort study.

BACKGROUND: Literature on the quality of life trends across time in children with atopic dermatitis are scarce. AIMS: To assess factors associated with quality of life of children with atopic dermatitis after a one-year follow-up and to examine the factors contributing to greater improvement in the atopic dermatitis-related quality of life over one year. METHODS: Our cohort consisted of 98 children who were treated for atopic dermatitis at the clinic of dermatovenereology. Data collection included atopic dermatitis scoring using the SCORing Atopic Dermatitis (SCORAD) index, Children's Dermatology Life Quality Index (CDLQI) for children aged > four years and Infants' Dermatitis Quality of Life Index (IDLQI) for children aged 0-4 years. Categorization of the impairment of quality of life score due to atopic dermatitis was as follows: mild (score from 0 to 6), moderate (score from 7 to 12) and severe (score from 13 to 30). The cohort was followed for one year after which a total of 80 children were reassessed. RESULTS: Improvements of both CDLQI and IDLQI were observed in children whose impairment of quality of life due to atopic dermatitis after one year was 'mild'. This was not observed in children whose atopic dermatitis caused either 'moderate' or 'severe impairment' of their quality of life. Adjusted analysis showed that lower initial SCORAD and greater improvement in SCORAD after the one-year follow-up were associated with a better quality of life at follow-up. LIMITATIONS: The size of our cohort was relatively small. Study participants were recruited from the largest urban and medical referral center in Serbia. Persons from suburban or rural regions may have had different perceptions of atopic dermatitis-related quality of life. CONCLUSION: Children with less severe atopic dermatitis were more likely to improve their atopic dermatitis-related quality of life. Lower SCORAD was associated with both better quality of life initially and greater improvement in quality of life after one year of follow-up.

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy.

The 10-year results after national introduction of pelvic lymph node staging in Danish intermediate-risk endometrial cancer patients not given postoperative radiotherapy. Gitte Ørtoft; Claus Høgdall; Estrid S Hansen; Margit Dueholm. OBJECTIVE: To prepare for the national introduction of sentinel node staging, we evaluated the consequences of the previous national decision to introduce lymph node staging in intermediate-risk endometrial cancer patients (grade 1/2 with > 50% or grade 3 with < 50% myometrial invasion) by determining the number of patients upstaged by lymphadenectomy and whether upstaging affected the survival and recurrence patterns of non-staged patients and patients with and without lymph node metastases. STUDY DESIGN: In a national cohort study, 2005-12, 1294 stage I-IV patients who should have been offered lymphadenectomy were progressively registered. The number of patients upstaged by lymphadenectomy, 10-year survivals were evaluated by Kaplan-Meier analysis and adjusted Cox regression. RESULTS: This study demonstrates that it takes time to introduce lymphadenectomy at a national level, as indicated by the increasing number of cases staged per year, from 12% in 2005 to 74% in 2012. Pelvic lymphadenectomy was performed in 43.8% (567/1294) and lymph node metastases were found in 13.6% (77/567). As 54 patients had further dissemination outside the uterine body, only 23 patients (6%) were upstaged from stage I to IIIC. Compared to lymph node-negative patients, the 77 patients with lymph node metastasis had significantly lower overall, (55% versus 68%), disease-specific (64% versus 86%), and progression-free survival (51% versus 77%), mainly due to non-local recurrences including a high number of paraaortic recurrences. In 873 final stage I intermediate-risk patients, 10-year survival and recurrence rates were not significantly lower in non-staged as compared to lymph node-negative patients (overall survival 62% versus 70%: disease-specific survival: 90% versus 90%, progression-free survival: 81% vs 83%), probably due to the low number of patients upstaged from stage I to stage IIIC. CONCLUSION: Lymph node metastases were present in 13.6% of patients with intermediate-risk who underwent pelvic lympadenectomy, and these patients had a lower 10-year survival than lymph node-negative patients. Because lymphadenectomy upstaged only 6% from stage I to stage IIIC, survival and recurrence rates were not significantly compromised in non-staged as compared to lymph node-negative intermediate-risk stage I patients. Sentinel node staging has now been implemented in Danish intermediate-risk endometrial cancer patients.

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study.

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

Parenthood among men diagnosed with cancer in childhood and early adulthood: trends over time in a Danish national cohort.

STUDY QUESTION: Is the rate of fatherhood among men diagnosed with cancer in childhood and early adulthood different from men without cancer, and, if so, have the differences changed over time? SUMMARY ANSWER: Men diagnosed with cancer have had significantly reduced rates of fatherhood compared with undiagnosed men; however, the rates of fatherhood among the cancer survivors have increased markedly over time. WHAT IS KNOWN ALREADY: The number of children and young adolescents who survive cancer has steadily increased over recent decades, with a current 5-year survival rate of approximately 80%. Consequently, life circumstances after cancer have gained increasing importance, including the desire among survivors to have children and a family. ARTs to aid reproduction among cancer survivors have been developed, and fertility preservation is increasingly a topic being discussed before undergoing cancer treatment. But the potential for fertility preservation differs dependent on age at diagnosis and type of cancer. Earlier studies have shown a decreased fertility rate among survivors of child and adolescent cancer compared to those diagnosed in early adulthood. STUDY DESIGN, SIZE, DURATION: This study is a national, register-based cohort study. Men diagnosed with cancer in childhood and early adulthood (<30 years of age) were registered in the Danish Cancer Register in 1978-2016 (n = 9353). According to the time of diagnosis, each cancer-diagnosed man was randomly matched with 150 undiagnosed men from the background population within the same birth year. The men were followed until having their first child, death, migration or the end of the study (31 December 2017) in medical registers and socio-demographic population registers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fatherhood among the boys and young men diagnosed with cancer were compared with the age-matched comparison group in all statistical analyses. Cancer diagnoses were categorised as central nervous system (CNS) cancers, haematological cancers or solid cancers. Analyses were stratified by age at diagnosis (0-9, 10-19, 20-29 years) and time of diagnosis (1978-1989, 1990-1999, 2000-2009, 2010-2016). Death was incorporated as a competing risk in all analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The study population consisted of 9353 boys and young men diagnosed with cancer between 1978 and 2016 and 1 386 493 men in the age-matched comparison group. Those surviving CNS cancer as young men had the lowest hazard ratio (HR) of fatherhood compared with the age-matched comparison group (HR 0.67, 95% CI 0.57-0.79), followed by survivors of haematological cancers (HR 0.90, 95% CI 0.81-1.01), while the highest chance of fatherhood was among survivors of solid cancers (HR 1.16, 95% CI 1.12-1.20) with a slightly increased HR compared with undiagnosed males. The HR of becoming a father increased over time. From the first decade to the last decade 30 years later, the HR of becoming a father increased for solid tumours (HR 0.78, 95% CI 0.73-0.83 to HR 1.08, 95% CI 0.95-1.22), haematological cancers (HR 0.64, 95% CI 0.53-0.79 to HR 0.97, 95% CI 0.73-1.30) and CNS cancers (HR 0.44, 95% CI 0.34-0.57 to HR 0.98, 95% CI 0.49-1.95) compared to the age-matched comparison group. Also, when compared with the age-matched comparison group, men diagnosed with cancer when aged 20-29 years were more likely became fathers over the time of the study (HR 0.80, 95% CI 0.74-0.86 to HR 1.08, 95% CI 0.96-1.22). LIMITATIONS, REASONS FOR CAUTION: The study was based on register data, and information was not available about the men's fertility potential, whether they had a desire to have children and whether it was possible for them to find a partner. Information about fertility preservation, e.g. sperm freezing, could also have provided additional insights. Furthermore, information about diagnosis and ART treatment would have been beneficial. WIDER IMPLICATIONS OF THE FINDINGS: Information and education of male patients diagnosed with cancer about fertility preservation options and their chances to create their own family is crucial. Reassuringly, time trends showed more men with a previous cancer diagnosis becoming fathers in recent years than in earlier years, reflecting that survival and fertility preservation have improved over time. STUDY FUNDING/COMPETING INTEREST(S): R.S. received a PhD grant from the Rosa Ebba Hansen Foundation and from the Health Foundation (J.nr. 15-B-0095). The funding for the establishment of the DANAC II Cohort was obtained from the Rosa Ebba Hansen Foundation. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of a self-help intervention to promote the health and wellbeing of marginalised people including those living with leprosy in Nepal: a prospective, observational, cluster-based, cohort study with controls.

BACKGROUND: People affected by leprosy are at increased risk of ulcers from peripheral nerve damage. This in turn can lead to visible impairments, stigmatisation and economic marginalisation. Health care providers suggest that patients should be empowered to self-manage their condition to improve outcomes and reduce reliance on services. Self-care involves carrying out personal care tasks with the aim of preventing disabilities or preventing further deterioration. Self-help, on the other hand, addresses the wider psychological, social and economic implications of leprosy and incorporates, for example, skills training and microfinance schemes. The aim of this study, known as SHERPA (Self-Help Evaluation for lepRosy and other conditions in NePAl) is to evaluate a service intervention called Integrated Mobilization of People for Active Community Transformation (IMPACT) designed to encourage both self-care and self-help in marginalised people including those affected by leprosy. METHODS: A mixed-method evaluation study in Province 5, Nepal comprising two parts. First, a prospective, cluster-based, non-randomised controlled study to evaluate the effectiveness of self-help groups on ulcer metrics (people affected by leprosy only) and on four generic outcome measures (all participants) - generic health status, wellbeing, social integration and household economic performance. Second, a qualitative study to examine the implementation and fidelity of the intervention. IMPACT: This research will provide information on the effectiveness of combined self-help and self-care groups, on quality of life, social integration and economic wellbeing for people living with leprosy, disability or who are socially and economically marginalised in low- and middle- income countries.

The outcome of laparoscopic assisted orchidopexy in very young children: A single hospital experience.

INTRODUCTION: Early orchidopexy has been linked to improved long term outcomes of fertility and reduced malignancy rates. However, the optimal age of intervention has been subject to change over the years. OBJECTIVE: This study aims to study males aged 6 months or less who undergo laparoscopic assisted orchidopexy for intraabdominal testes to establish the safety, efficacy, and benefit in the defined age group. STUDY DESIGN: We prospectively assessed 19 boys at or below 6 months of age, who had laparoscopic assisted orchidopexy for intraabdominal undescended testes at Salmaniya Medical Complex in Bahrain between January 2014 and December 2018. We examined: demographics, laterality, testicular locations, testicular volumes, operative time, complications, and durations of hospitalization and follow-up. Ultrasound-derived testicular volumes were assessed before and after orchidopexy. They were calculated using the Hansen formula (Testicular volume = 0.52 × length [L] × width [W]2 [1]. They were then compared with reference ranges from a Dutch cohort study of 769 healthy boys. Successful outcomes were correct intrascrotal position with minimal complications and normal testicular volumes. RESULTS: A total of 19 males were operated at a mean age of 5.6 months and followed for a mean of 2.35 years. Of these, 7 had left-sided and 12 had right-sided cryptorchidism. Testicular locations were noted intra-operatively; 10 were above the internal ring, 5 near the iliac vessels, and 4 close to the kidney. The mean operative time was 59.58 minutes. Only 2 minor complications occurred and no cases of testicular atrophy. None of the patients required hospital-stay beyond 24 hours. The success rate was 89.46% in achieving correct scrotal position. Testicular volumes were normal before and after orchidopexy. They significantly increased after orchidopexy (P ≤ 0.05). The testicular growth rate after 24 months was slightly higher than normal. DISCUSSION: In line with previous studies we were 89.46% successful in re-positioning testes [2]. In contrast to studies intervening at older ages which associated intra-abdominal testes with greater risks of complications, we found few minor complications and no testicular atrophy [3,4]. Testicular volumes in the affected testes were normal, contrary to decreased volumes found by other researchers [5]. Limitations of this study are the small number of patients and short follow-up which limits assessment of long-term outcomes. CONCLUSION: Early orchiopexy is safe and effective. Laparoscopic assisted orchidopexy at an early age was beneficial and resulted in normal testicular volumes before and after surgery.

Evaluating the health effect of a Social Housing programme, Minha Casa Minha Vida, using the 100 million Brazilian Cohort: a natural experiment study protocol.

INTRODUCTION: Social housing programmes have been shown to influence health, but their effects on cardiovascular mortality and incidence of infectious diseases, such as leprosy and tuberculosis, are unknown. We will use individual administrative data to evaluate the effect of the Brazilian housing programme Minha Casa Minha Vida (MCMV) on cardiovascular disease (CVD) mortality and incidence of leprosy and tuberculosis. METHODS AND ANALYSIS: We will link the baseline of the 100 Million Brazilian Cohort (2001-2015), which includes information on socioeconomic and demographic variables, to the MCMV (2009-2015), CVD mortality (2007-2015), leprosy (2007-2015) and tuberculosis (2007-2015) registries. We will define our exposed population as individuals who signed the contract to receive a house from MCMV, and our non-exposed group will be comparable individuals within the cohort who have not signed a contract for a house at that time. We will estimate the effect of MCMV on health outcomes using different propensity score approaches to control for observed confounders. Follow-up time of individuals will begin at the date of exposure ascertainment and will end at the time a specific outcome occurs, date of death or end of follow-up (31 December 2015). In addition, we will conduct stratified analyses by the follow-up time, age group, race/ethnicity, gender and socioeconomic position. ETHICS AND DISSEMINATION: The study was approved by the ethic committees from Instituto Gonçalo Muniz-Oswaldo Cruz Foundation and University of Glasgow Medical, Veterinary and Life Sciences College. Data analysis will be carried out using an anonymised dataset, accessed by researchers in a secure computational environment according to the Centre for Integration of Data and Health Knowledge procedures. Study findings will be published in high quality peer-reviewed research journals and will also be disseminated to policy makers through stakeholder events and policy briefs.