Catastrophic Anti-Phospholipid Syndrome in Systemic Lupus Erythematosus: A Tsunami in the Ocean.

Antiphospholipid anti body syndrome is an autoimmune disorder characterized by arterial or venous thrombosis and/or pregnancy morbidity with foetal deaths or abortions in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid antibody syndrome (CAPS) is an accelerated form of disease with rapid involvement of multiple organ systems often posing a diagnostic challenge. There is a paucity of literature on the presentations of CAPS owing to the orphan nature of the disease. MATERIAL: We present three cases of CAPS in patients with systemic lupus erythematosus (SLE). OBSERVATION: Case 1 - A 22-year-old lady with SLE presented with anasarca, abnormal mentation, anaemia, thrombocytopenia, ANA (IIF) 4+ speckled, positive lupus anticoagulant with pulmonary thromboembolism involving right middle and left lower lobes. While in hospital, she developed infarct in left middle cerebral artery territory; was managed with IVIg, anticoagulation, pulse methylprednisolone and cyclophosphamide. She had a refractory course with cytokine storm syndrome, neutropenic sepsis and eventually succumbed to her illness. Case 2 - A 23-year-old lady presented with a history of oral ulcers, alopecia, photosensitive malar rash, polyarthritis of small joints of hands, Raynaud's phenomenon, intermittent fever with headache and arterial thrombosis resulting in gangrene of the right thumb. She had ANA (IIF) 3+ speckled, raised anti-ds-DNA, positive for lupus anticoagulant; was managed as SLE with hydroxychloroquine and prednisolone. She returned to hospital with generalized tonic-clonic seizures, papilledema but no focal neurological deficit. MRI brain showed superior sagittal sinus thrombosis; was managed with pulse methylprednisolone, anti-coagulation, anti-epileptic drugs, cyclophosphamide and hydroxychloroquine; patient survived. Case 3 - A 47- year-old lady with SLE and Lupus Nephritis Class IV on Euro-Lupus regime presented with paraparesis, cold and clammy left lower limb with absent femoral, popliteal, anterior tibial and dorsalis pedis pulses. CT angiography showed thrombosis infra-renal abdominal aorta and in the left popliteal artery; was positive for high titre ß2-GPI IgM. She was managed with pulse methylprednisolone, anti-coagulation, broad-spectrum antibiotics but developed sudden haemodynamic deterioration after the first cycle of plasmapheresis and was switched to IVIg. However, she developed cardiac arrest and succumbed before MR angiography for suspected anterior spinal artery thrombosis and amputation for left lower limb. CONCLUSION: In our cases, timely diagnoses were made based on a high index of suspicion and were managed with a combination of IVIg, systemic glucocorticoids, plasmapheresis and other supportive measures. However, despite providing the standard of care, we encountered poor outcome in two patients, highlighting the high mortality associated with CAPS.

Clinical Profile and Outcome of Surgery of Patients with Hydatid Cysts at the National Referral Hospital, Bhutan: An Observational Study.

Background Hydatid disease a zoonosis caused by tapeworms (cestodes) of genus Echinococcus. Humans acquire this infection by ingestion of eggs of Echinococcus from infected dogs, sheep, goat, cattle or pigs. Hydatid cyst causes significant morbidity, mortality and socioeconomic loss. Objective The objective of this study was to describe the clinical profile and short-term outcome of surgical treatment of hydatidosis at Bhutan's largest hospital. Method This was a descriptive study conducted among patients ≥ 18 years at the National Referral Hospital, Thimphu, Bhutan from 01 January to 31 December 2017. Data on pre-surgery treatment, type and outcome of surgery and histopathology were collected. Data was entered analysed in EpiData. All variables are presented using descriptive statistics. Ethics approval was obtained from the Research Ethics Board of Health, Ministry of Health, Bhutan. Result There were 38 patients who underwent surgeries. The mean age of the sample was 36 (±17) years; cases were reported from almost all districts in the country. The most common symptoms at presentation was abdominal pain (27, 71.4%), nausea (21, 55.3%), abdominal distension (16, 41.1%). The median duration of symptoms was 6.0 months (IQR 3.0, 12.0). Liver was involved in 36 patients (94.7%). All underwent de-roofing and drainage through laparotomy (35; 92.1%), laparoscopy (2, 5.3%) or throracotomy (1, 2.6%). Histopathologic confirmation was obtained in 28 patients (73.7%). Twenty-three patients (60.5%) suffered from minor post-operative complications. Conclusion Patients with hydatid cyst present with abdominal pain, nausea abdominal distension. They suffer with symptoms for long periods till surgical treatment. The majority had favourable outcomes of surgery.

Changes in flowering functional group affect responses of community phenological sequences to temperature change.

Our ability to predict how temperature modifies phenology at the community scale is limited by our lack of understanding of responses by functional groups of flowering plants. These responses differ among species with different life histories. We performed a reciprocal transplant experiment along four elevation gradients (e.g., 3,200, 3,400, 3,600 and 3,800 m) to investigate the effects of warming (transferred downward) and cooling (transferred upward) on plant flowering functional groups (FFGs) and community phenological sequences (i.e., seven phenological events). Warming significantly decreased early-spring-flowering (ESF) plant coverage and increased mid-summer-flowering plant (MSF) coverage, while cooling had the opposite effect. All community phenological events were advanced by warming and delayed by cooling except for the date of complete leaf-coloring, which showed the opposite response. Warming and cooling could cause greater advance or delay in early-season phenological events of the community through increased coverage of MSF species, and warming could delay late-season phenological events of the community by increased coverage of ESF species. These results suggested that coverage change of FFGs in the community induced by temperature change could mediate the responses of the community phenological events to temperature change in the future. The response of phenological events to temperature change at the species level may not be sufficient to predict phenological responses at the community-level due to phenological compensation between species in the community.

Relatively stable response of fruiting stage to warming and cooling relative to other phenological events.

The timing of the fruit-set stage (i.e., start and end of fruit set) is crucial in a plant's life cycle, but its response to temperature change is still unclear. We investigated the timing of seven phenological events, including fruit-set dates during 3 yr for six alpine plants transplanted to warmer (approximately +3.5°C in soils) and cooler (approximately -3.5°C in soils) locations along an altitudinal gradient in the Tibetan area. We found that fruit-set dates remained relatively stable under both warming and cooling during the 3-yr transplant experiment. Three earlier phenological events (emergence of first leaf, first bud set, and first flowering) and two later phenological events (first leaf coloring and complete leaf coloring) were earlier by 4.8-8.2 d/°C and later by 3.2-7.1 d/°C in response to warming. Conversely, cooling delayed the three earlier events by 3.8-6.9 d/°C and advanced the two later events by 3.2-8.1 d/°C for all plant species. The timing of the first and/or last fruit-set dates, however, did not change significantly compared to earlier and later phenological events. Statistical analyses also showed that the dates of fruit set were not significantly correlated or had lower correlations with changes of soil temperature relative to the earlier and later phenological events. Alpine plants may thus acclimate to changes in temperature for their fruiting function by maintaining relatively stable timings of fruit set compared with other phenological events to maximize the success of seed maturation and dispersal in response to short-term warming or cooling.

Diversity and phylogeny of mitochondrial DNA isolated from mithun Bos frontalis located in Bhutan.

We sequenced the 16S rRNA gene in mitochondrial DNA to characterize mithun located in Bhutan and to increase our understanding of its origin. We compared mithun with yak, European cattle, Bhutanese zebu and Indian zebu. Sequencing revealed low nucleotide diversity within the mithun population and their phylogenetic proximity to gaur. A close relationship between Bhutanese mithun and gaur was confirmed by an additional comparison with wild gaur specimens from three locations in Bhutan. Direct domestication of mithun from gaur was supported, while maternal contribution from the cattle lineage during domestication was not supported.

Construction of Multiple Choice Questions Before and After An Educational Intervention.

INTRODUCTION: Khesar Gyalpo University of Medical Sciences of Bhutan, established in 2014, has ushered in a new era in medical education in Bhutan. Multiple Choice Questions are a common means of written assessment in medical education. METHODS: This was a quasi-experimental study conducted at the Faculty of Postgraduate Medicine, KGUMSB, Thimphu in December 2016. A total of 8 MCQs were prepared by four teaching faculties from different fields who had no prior training on construction of MCQs. It was delivered to a group of 16 randomly selected intern doctors. A 2 hours long workshop on construction of MCQs was conducted. After the workshop, the same MCQs were modified according to standard guidelines on developing MCQs and were tested in the same group of intern doctors. An analysis on the performance, difficulty factor, discrimination index and distractor analysis was done on the two sets of MCQs using Microsoft Excel and SPSS 20.0. RESULTS: For the pre- and post-workshop questions respectively, the pass percentage was 69.8% (11) and 81.3% (13), difficulty factor was 0.51 and 0.53, discrimination index was 0.59 and 0.47, distractor effectiveness was 83.3% and 74.9%. CONCLUSIONS: The workshop on MCQ development apparently seemed highly valuable and effective in changing the learning and performances of medical educators in the development of MCQs.

Providing a gateway to prevention and care for the most at-risk populations in Bhutan: is this being achieved?

SETTING: Two free-standing urban human immunodeficiency virus (HIV) testing and counselling (HCT) centres in Bhutan offering services to the general population and targeting the most at-risk populations (MARPs). OBJECTIVES: To assess the trend in testing for HIV, hepatitis B and syphilis in both the general population and MARPs, and to determine if sociodemographic and risk behaviour characteristics are associated with HIV, hepatitis B and syphilis seropositivity. DESIGN: Cross-sectional study using client records, 2009 - 2012. RESULTS: Of 7894 clients, 3009 (38%) were from the general population, while 4885 (62%) were from MARPs. Over the 4-year period, testing declined progressively among the general population, while it increased or remained static for MARPs. Of 4885 MARPs, seropositivity was respectively 0.7%, 1.3% and 1.2% for HIV, hepatitis B and syphilis. Female sex workers (FSWs) (relative risk [RR] 4.4, P = 0.03) and partners of person living with HIV (RR 25.9, P < 0.001) had a higher risk of being HIV-positive. FSWs had also a greater risk of being syphilis-positive (RR 9.1, P < 0.001). CONCLUSION: The increase in uptake of HCT services by MARPs is a welcome finding; however, the relatively static trends call for the introduction of community outreach approaches. The critical gateway being provided to MARPs is an 'opportunity' for the expansion of the current service package.

Contexte : Deux centres indépendants de dépistage et conseil pour le VIH (HCT) au Bhoutan proposant leurs services à la population générale et ciblent les plus à risque (MARP).Objectifs : Evaluer la tendance des tests VIH, hépatite et syphilis dans la population générale et chez les MARP et déterminer si les caractéristiques sociodémographiques et les conduites à risque sont associées à la séropositivité pour le VIH, l'hépatite et la syphilis.Schéma : Etude transversale sur les dossiers des clients, de 2009 à 2012.Résultats :Sur 7894 clients, 3009 (38%) appartenaient à la population générale et 4885 (62%) aux MARP. Au cours des 4 années, les examens ont diminué pour la population générale tandis qu'ils augmentaient ou restaient stables pour les MARP. Sur 4885 MARP, la séropositivité était de 0,7% pour le VIH, 1,3% pour l'hépatite B et 1,2% pour la syphilis. Les professionnelles du sexe (risque relatif [RR] 4,4 ; P = 0,03) et les partenaires de personnes vivant avec le VIH (RR 25,9 ; P < 0,001) avaient davantage de risques d'être VIH positif. Les professionnelles du sexe aveint également un risque plus élevé d'être positives pour la syphilis (RR 9,1 ; P < 0,001).Conclusion : L'augmentation de l'utilisation des services de HCT par les MARP est un résultat bienvenu, mais la tendance relativement stationnaire demande l'introduction d'approches de stratégie avancées dans les communautés. La porte d'entrée critique offerte aux MARP est une « opportunité ¼ d'accroitre le paquet de services actuels.

Marco de referencia: Dos centros independientes de diagnóstico y orientación de la infección por el virus de la inmunodeficiencia humana (VIH) en Bután, que prestan servicios a la población general, con una orientación especial hacia la población de más alto riesgo (MARP).Objetivos: Evaluar la tendencia en la práctica de las pruebas diagnósticas del VIH, la hepatitis B y la sífilis en la población general y en los MARP y analizar si existen factores sociodemográficos y comportamentales que se asocien con la positividad del examen serológico de estas infecciones.Métodos: Fue este un estudio transversal a partir de los registros de los usuarios de los centros entre el 2009 y el 2012.Resultados: De los 7894 usuarios, 3009 (38%) formaban parte de la población general y 4885 (62%) pertenecían a los MARP. Durante el período de 4 años, la práctica de las pruebas diagnósticas disminuyó de manera progresiva en la población general, pero aumentó o permaneció estable en los MARP. En las 4885 personas del grupo con mayor riesgo, la seropositividad fue 0,7% frente al VIH, 1,3% a la hepatitis B y 1,2% a la sífilis. Se observó un riesgo más alto de obtener un resultado positivo al VIH en las mujeres profesionales del sexo (riesgo relativo [RR] 4,4; P = 0,03) y en las parejas de las personas resultados positivos a la serología del VIH (RR 25,9; P < 0,001). Las profesionales del sexo exhibieron un mayor riesgo de obtener una serología positiva de la sífilis (RR 9,1; P < 0,001).Conclusión: El aumento de la utilización de los servicios de diagnóstico y orientación del VIH por parte de las poblaciones con más alto riesgo constituye una observación afortunada, pero la estabilización de las tendencias invita a introducir estrategias de extensión a la comunidad. La pasarela crucial que se está ofreciendo a la población en mayor riesgo de contraer estas enfermedades representa una 'oportunidad' de difusión del conjunto de servicios que se prestan en la actualidad.

The burden and treatment outcomes of extra-pulmonary tuberculosis in Bhutan.

SETTING: All tuberculosis (TB) registration sites in Bhutan. DESIGN: Cross-sectional study involving a retrospective review of TB registers and TB treatment cards. OBJECTIVES: To determine: 1) the number and proportion of all TB cases registered as extra-pulmonary TB (EPTB) from 2001 to 2010, 2) the age and sex of the patients and the categories and types of EPTB registered in 2010, and 3) their treatment outcomes. RESULTS: The proportion of all TB cases registered as EPTB over a period of 10 years varied from 30% to 40%. In 2010, 505 patients were registered with EPTB, of whom 50% were male, 21% were children, and 96% were new EPTB cases. TB lymph node enlargement and pleural effusion were the two most common types of EPTB, accounting for 67%, followed by abdominal TB and spinal/bone/kidney disease. The overall treatment success rate was 90%, and was generally similar with respect to sex, age and different types of EPTB. CONCLUSION: Bhutan has a high proportion of patients registered as having EPTB, for whom treatment outcomes are satisfactory. Further work is needed to better understand how EPTB is diagnosed throughout the country.

Childhood tuberculosis in Bhutan: profile and treatment outcomes.

SETTING: All hospitals and health centres under the National Tuberculosis Control Programme (NTCP) in Bhutan. OBJECTIVE: To describe the number and proportion of childhood tuberculosis (TB) cases registered under the NTCP in 2010, their demographic and clinical characteristics and any associations with treatment outcomes. DESIGN: Retrospective cohort study involving a review of TB treatment cards and registers. RESULTS: Of 1332 TB cases registered, 187 (14%) were children aged <15 years, 75 (40%) were aged <5 years, and 180 (96%) were new cases; nearly half were extra-pulmonary TB, with lymphadenitis being the most common form. The overall treatment success rate was 93%, and none of the demographic and clinical characteristics were associated with treatment outcomes. A few recording deficiencies were identified. CONCLUSION: TB in children is well recognised in Bhutan, and their treatment outcomes were excellent.

The kingdom of Bhutan health system review

The predominantly public financed and managed health system in Bhutan has evolved and grown remarkably in the past five and a half decades. Health services are available through a three-tier structure, i.e. primary, secondary and tertiary levels. Traditional and allopathic medicine services are integrated and delivered under one roof. Village health workers play an important role as a bridge between health services and the community to promote health. Programmes are in place to address the public health challenges facing the country. Health services are free as enshrined in the Constitution of Bhutan. Therefore, government revenue is the predominant source of health financing. In 2014, the total health expenditure (THE) was 3.6% of the gross domestic product (GDP). Despite the difficult geographical terrain and dispersed population settlements, access to health services has improved remarkably. Bhutan is among the top global performers in gains in life expectancy in the past 40 years. The targets of MDGs 4 and 5 have been achieved and since 2010, immunization levels have been maintained over 95%. However, the country faces multiple burden of health challenges. While communicable diseases remain a substantial burden, noncommunicable diseases (NCDs) are increasing. A few other emerging, challenging issues are crime, substance dependence and suicide/other mental health problems. Health equity requires attention as disparities exist in access to and utilization of health services as well as in health outcomes between urban and rural areas, income levels, districts and between western, central and eastern regions. Variations in efficiency levels among different districts and health facilities highlight the potential for improvement in overall efficiency. Though there is good evidence of intersectoral action, it needs to be fostered further to close the existing equity gaps and achieve the Sustainable Development Goals (SDGs).