Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder.

Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Use of complementary and alternative medicine by cancer patients in Colombia.

BACKGROUND: The use of complementary and alternative medicines (CAM) among cancer patients varies greatly. The available data suggest an increasing use of CAM over time and a higher prevalence in low- and middle-income countries. However, no reliable data are available from Latin America. Accordingly, we examined the prevalence of CAM use among cancer patients from six Colombian regions. METHODS: We conducted a survey on cancer patients attending comprehensive cancer centres in six capital cities from different regions. The survey was designed based on a literature review and information gathered through focus groups on CAM terminology in Colombia. Independent random samples of patients from two comprehensive cancer centres in every city were obtained. Patients 18 years and older with a histopathological diagnosis of cancer undergoing active treatment were eligible. The prevalence of CAM use is reported as a percentage with the corresponding confidence interval. CAM types are reported by region. The sociodemographic and clinical characteristics of CAM users and non-users were compared using Chi square and t tests. RESULTS: In total, 3117 patients were recruited. The average age 59.6 years old, and 62.8% were female. The prevalence of CAM use was 51.7%, and compared to non-users, CAM users were younger, more frequently women, affiliated with the health insurance plan for low-income populations and non-Catholic. We found no differences regarding the clinical stage or treatment modality, but CAM users reported more treatment-related side effects. The most frequent types of CAM were herbal products, specific foods and vitamins, and individually, soursop was the most frequently used product. Relevant variability between regions was observed regarding the prevalence and type of CAM used (range: 36.6% to 66.7%). The most frequent reason for using CAM was symptom management (30.5%), followed by curative purposes (19.5%). CONCLUSIONS: The prevalence of CAM use among cancer patients in Colombia is high in general, and variations between regions might be related to differences in cultural backgrounds and access to comprehensive cancer care. The most frequently used CAM products and practices have little scientific support, suggesting the need to enhance integrative oncology research in the country.

New STAG3 gene variant as a cause of premature ovarian insufficiency / Nueva variante del gen STAG3 causante de insuficiencia ovárica prematura

Objectives: To describe a case of ovarian failure secondary to a homozygous pathogenic variant in the STAG3 gene not previously reported. Materials and Methods: A 16-year-old patient with primary amenorrhea and absence of secondary sexual characteristics, with documented autoimmune hypothyroidism, poor genital and gonadal streak development which prompted the performance of clinical exome sequencing. A homozygous pathogenic variant not previously reported in the STAG3 gene, which has been associated with premature ovarian insufficiency (POI), was identified. Conclusions: In this case, clinical exome sequencing was key for identifying a STAG gene abnormality, probably associated with POI and long term prognosis for the patient. A new pathogenic variant c.2773delT; p.Ser925Profs*6 of the STAG3 gene associated with POI was established.

Objetivos: describir un caso de falla ovárica secundaria a una variante patogénica homocigota en el gen STAG3 no reportada previamente. Materiales y métodos: paciente de 16 años con amenorrea primaria y ausencia de características sexuales secundarias, en quien se documentó hipotiroidismo autoinmune, pobre desarrollo genital y cintilla gonadal, por lo cual se realizó secuenciación de exoma clínico. Se identificó una variante homocigota patogénica previamente no reportada en el gen STAG3, el cual ha sido relacionado con insuficiencia ovárica prematura (IOP). Conclusiones: en este caso, la realización de exoma clínico fue determinante para identificar una alteración del gen STAG, probablemente asociada a la IOP y el pronóstico a largo plazo de la paciente. Se establece una nueva variante patogénica c.2773delT; p.Ser925Profs*6 del gen STAG3 asociada a la IOP.

COVID-19 Vaccine Hesitancy and Emerging Variants: Evidence from Six Countries.

As the world tries to cope with the devastating effects of the COVID-19 pandemic and emerging variants of the virus, COVID-19 vaccination has become an even more critical tool toward normalcy. The effectiveness of the vaccination program and specifically vaccine uptake and coverage, however, is a function of an individual's knowledge and individual opinion about the disease and available vaccines. This study investigated the knowledge, attitudes, and resulting community practice(s) associated with the new COVID-19 variants and vaccines in Bangladesh, Colombia, India, Malaysia, Zimbabwe, and the USA. A cross-sectional web-based Knowledge, Attitudes, and Practices (KAP) survey was administered to respondents living in six different countries using a structured and multi-item questionnaire. Survey questions were translated into English, Spanish, and Malay to accommodate the local language in each country. Associations between KAP and a range of explanatory variables were assessed using univariate and multiple logistic regression. A total of 781 responses were included in the final analysis. The Knowledge score mean was 24 (out of 46), Attitude score 28.9 (out of 55), and Practice score 7.3 (out of 11). Almost 65% of the respondents reported being knowledgeable about COVID-19 variants and vaccination, 55% reported a positive attitude toward available COVID-19 vaccines, and 85% reported engaging in practices that supported COVID-19 vaccination. From the multiple logistic models, we found post-graduate education (AOR = 1.83, 95% CI: 1.23-2.74) and an age range 45-54 years (AOR = 5.81, 95% CI: 2.30-14.69) to be significantly associated with reported COVID-19 knowledge. In addition, positive Attitude scores were associated with respondents living in Zimbabwe (AOR = 4.49, 95% CI: 2.04-9.90) and positive Practice scores were found to be associated with people from India (AOR = 3.68, 95% CI: 1.15-11.74) and high school education (AOR = 2.16, 95% CI: 1.07-4.38). This study contributes to the identification of socio-demographic factors associated with poor knowledge, attitudes, and practices relating to COVID-19 variants and vaccines. It presents an opportunity for collaboration with diverse communities to address COVID-19 misinformation and common sources of vaccine hesitancy (i.e., knowledge, attitudes, and practices).

Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence.

OBJECTIVE: To determine if the repeated occurrence of manic episodes in bipolar I disorder (BD-I) patients is associated with reduced cognitive performance, which could in turn imply a worsening in the disorder's evolution. METHOD: Cognitive performance in euthymic patients was assessed using attention, memory, and executive function tests on 24 BD-I patients who had experienced only 1 manic episode, on 27 BD-I patients with 2 manic episodes, on 47 BD-I patients with 3 or more manic episodes, and on 66 healthy control subjects. RESULTS: In BD-I patients, number of manic episodes was positively associated with poorer performance on neurocognitive tests, an association that was not accounted for by depression, disease chronicity, onset, or medication. Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more. CONCLUSION: The number of manic episodes predicted poor cognitive performance, suggesting that the recurrence of mania may have a long-term neuropsychological impact. Prospective follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function.

Evidence for a role of the NOS1AP (CAPON) gene in schizophrenia and its clinical dimensions: an association study in a South American population isolate.

BACKGROUND/AIMS: Recent studies have implicated a region on chromosome 1q21-23, including the NOS1AP gene, in susceptibility to schizophrenia. However, replication studies have been inconsistent, a fact that could partly relate to the marked psychopathological heterogeneity of schizophrenia. The aim of this study is to evaluate association of polymorphisms in the NOS1AP gene region to schizophrenia, in patients from a South American population isolate, and to assess if these variants are associated with specific clinical dimensions of the disorder. METHODS: We genotyped 24 densely spaced SNPs in the NOS1AP gene region in a schizophrenia trio sample. The transmission disequilibrium test (TDT) was applied to single marker and haplotype data. Association to clinical dimensions (identified by factor analysis) was evaluated using a quantitative transmission disequilibrium test (QTDT). RESULTS: We found significant association between eight SNPs in the NOS1AP gene region to schizophrenia (minimum p value = 0.004). The QTDT analysis of clinical dimensions revealed an association to a dimension consisting mainly of negative symptoms (minimum p value 0.001). CONCLUSIONS: Our findings are consistent with a role for NOS1AP in susceptibility to schizophrenia, especially for the 'negative syndrome' of the disorder.

Stroke as a complication of Coronavirus disease 2019 (COVID-19).

Not available.

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants.

Safety and efficacy of Vecchietti vaginoplasty in vaginal agenesis: cohort study. Medellín, Colombia 2007-2012 / Seguridad y eficacia de la vaginoplastia de Vecchietti en agenesia vaginal: estudio de cohorte, en Medellín, Colombia, 2007 a 2012

Objective: To describe the Vecchietti vaginoplasty technique (VVT) in patients diagnosed with secondary vaginal agenesis and to analyze the safety and efficacy of this technique. Materials and methods: Historical cohort of patients with vaginal agenesis secondary to Mayer- Rokitansky-Kuster-Hauser and androgen insensitivity syndromes, subjected to vaginoplasty using the Vecchietti technique at San Vicente Fundación University Hospital, a high complexity referral institution located in the city of Medellín, during the time period between 2007 and 2012. Patients with functional a vagina for intercourse were excluded. Sampling was consecutive. Sociodemographic, clinical, safety and efficacy variables were measured. Descriptive statistics were used. Results: The main complaint was primary amenorrhea (69.2%). Associated malformations included right renal agenesis (15.4%) and skeletal malformations (15.4%). There was one intra-operative bladder perforation and, postoperatively, there were three (23.1%) minor complications. At 1-year follow-up, a functional vagina had been obtained in 84.6% of cases. Conclusion: Vecchietti vaginoplasty is a simple surgical technique resulting in satisfactory functional outcomes with only minor complications. Further studies with control groups are required in order to better assess the efficacy of the various techniques used for neovagina creation.

Objetivo: describir la técnica de vaginoplastia de Vecchietti (TVV) en pacientes diagnosticadas con agenesia vaginal secundaria y hacer una aproximación a la seguridad y eficacia de esta técnica. Materiales y métodos: cohorte histórica de pacientes con agenesia vaginal secundaria al síndrome de Mayer-Rokitansky-Kuster-Hauser y al síndrome de insensibilidad androgénica, a quienes se les realizó vaginoplastia por técnica de Vecchietti en el Hospital Universitario San Vicente Fundación, institución de referencia, de alta complejidad, en el periodo 2007 a 2012. Se excluyeron quienes tenían una vagina funcional para relaciones coitales. Muestreo consecutivo. Se midieron variables sociodemográficas, clínicas, de seguridad y de eficacia. Se utilizó estadística descriptiva. Resultados: el principal motivo de consulta fue la amenorrea primaria (69,2 %). Las malformaciones asociadas fueron agenesia renal derecha (15,4 %) y malformaciones esqueléticas (15,4 %). Se presentó una perforación intraoperatoria de la vejiga y tres complicaciones menores (23,1 %) en el posoperatorio. En el 84,6 % de ellas se obtuvo una vagina funcional a un año de seguimiento. Conclusiones: la TVV es una técnica quirúrgica simple que ha permitido obtener resultados funcionales satisfactorios con complicaciones menores. Se requieren estudios con grupo control para tener una mejor evaluación de la eficacia de las diferentes técnicas de construcción de la neovagina.

Cuidados paliativos en la atención primaria de salud

En la actualidad, la oferta de cuidados paliativos especializados ha sido superada por la demanda, por lo cual la atención a pacientes con enfermedades en estado terminal o en fase final de la vida suele estar a cargo del médico del nivel primario de asistencia. En ese sentido, los cuidados paliativos primarios incluyen el diagnóstico, el tratamiento paliativo, la planificación anticipada, la gestión y coordinación de intervenciones multidisciplinarias y la transferencia a cuidados especializados cuando sea necesario y haya disponibilidad para ello. Al respecto, en este artículo se exponen brevemente algunos elementos sobre el tema y se propone, además, un algoritmo práctico y fácil de aplicar en la atención primaria, que permitirá identificar a la población aquejada por dolencias en esas etapas, con diferenciación en cuanto a afecciones neoplásicas o no neoplásicas.

Nowadays, the offer of specialized palliative care has been overcome by the demand, reason why care to patients with terminal illness or in end-of-life period is usually in charge of the doctor from primary care level. In that sense, primary palliative care includes the diagnosis, palliative treatment, early planning, administration and coordination of multidisciplinary interventions and referring to specialized care when it is necessary and the service is available. In this respect, some elements on the topic are shortly exposed in this work and, also, a practical and easy implementation algorithm in primary care is proposed that will allow identifying population suffering from pain in those stages, with differentiation as for neoplastic or non neoplastic affections.

Spatial distribution of Zika in Honduras during 2016-2017 using geographic information systems (GIS) - Implications for public health and travel medicine.

BACKGROUND: Zika virus (ZIKV) infection has significantly affected Latin America in 2015-2017. Most studies have been reported from Brazil and Colombia, and only a few from Central America. For these reasons, we analyzed the incidence, incidence rates and evolution of cases in Honduras from 2016 to 2017. METHODS: Using epidemiological weeks (EW) surveillance data on the ZIKV epidemics in Honduras, we estimated incidence rates (cases/100,000 population), and developed maps at national, departmental and municipal levels. RESULTS: From 1 January 2016 to 31 December 2017, a total of 32,607 cases of ZIKV were reported (98.5% in 2016 for an incidence rate of 36.85 cases/100,000 pop; 1% confirmed by RT-PCR). The highest peak was reached on the EW 6°, 2016 (2559 cases; 29.34 cases/100,000 pop). The department with the highest number of cases and incidence rate was Cortés (13,128 cases, 791.08 cases/100,000 pop in 2016). DISCUSSION: The pattern and evolution of ZIKV infection in Honduras have been similar to that which occurred for chikungunya in 2015. As previously reported, infection with chikungunya involved predominantly the central and capital area of the country, reaching incidences there >750 cases/100,000 pop. Studies using geographical information systems linked with clinical disease characteristics are necessary to attain accurate epidemiological data for public health systems. Such information is also useful for assessment of risk for travelers who visit specific areas in a destination country.

Prescription patterns and costs of antidiabetic medications in a large group of patients.

AIMS: To determine the prescription patterns of antidiabetic medications and the variables associated with their use in a Colombian population. METHODS: A cross-sectional study using a systematized database of approximately 3.5 million affiliates of the Colombian Health System. Patients of both genders and all ages treated uninterruptedly with antidiabetic medications for three months (June-August 2015) were included. A database was designed that included sociodemographic, pharmacological, comedication, and cost variables. RESULTS: A total of 47,532 patients were identified; the mean age was 65.5 years, and 56.3% were women. Among the patients, 56.2% (n=26,691) received medication as monotherapy. The most prescribed medications were metformin, 81.3% (n=38,664), insulins, 33.3% (n=15,848), and sulfonylureas, 21.8% (n=10,370). Among the patients, 92.8% received comedications, including antihypertensives (79.7%), hypolipemiants (65.5%), antiplatelet drugs (56.3%), analgesics (33.9%), antiulcerants (33.1%), and thyroid hormone (17.3%). The cost per 1000 inhabitants/day was $1.21 USD for metformin, $3.89 USD for insulins, and $0.02 USD for glibenclamide. CONCLUSIONS: Generally, rational prescription habits predominated, however in some cases an overuse of comedications (such as antiulcer drugs) and a large group of patients with high cost formulations were observed. Subsequent effectiveness and cost-benefit analyzes are required.