Molecular Characterization and Clinical Relevance of Taxonomic Reassignment of Staphylococcus schleiferi Subspecies into Two Separate Species, Staphylococcus schleiferi and Staphylococcus coagulans.

Staphylococcus schleiferi is an opportunistic pathogen in humans and dogs. Recent taxonomic reassignment of its subspecies (S. schleiferi subsp. schleiferi and S. schleiferi subsp. coagulans) into two separate species (S. schleiferi and S. coagulans) lacks supporting data for diagnostic implications and clinical relevance. We aimed to confirm the reclassification of S. schleiferi by using genomic and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) data for a large set of isolates from humans and animals to investigate their molecular epidemiology and clinical relevance. Routine MALDI-TOF analysis and Illumina sequencing were performed on 165 S. schleiferi isolates from the Netherlands. With 33 publicly available genomes, the study included 198 genomes from 149 dogs, 34 humans, and 15 other sources. The Type Strain Genome Server was used to identify species in the genomes, and the MALDI-TOF MS database was extended to improve species differentiation. MALDI-TOF did not discriminate between S. schleiferi and S. coagulans. Genome phylogeny distinguished the two species in two monophyletic clusters. S. schleiferi isolates originated from humans, while S. coagulans isolates were found in animals and three human isolates clustering with the animal isolates. The sialidase B gene (nanB) was a unique marker gene for S. schleiferi, whereas the chrA gene was exclusive for S. coagulans. The mecA gene was exclusively detected in S. coagulans, as were the lnu(A), blaZ, erm(B/C), tet(O/M), and aac(6')-aph(2'') genes. The MALDI-TOF database extension did not improve differentiation between the two species. Even though our whole-genome sequencing-based approach showed clear differentiation between these two species, it remains critical to identify S. schleiferi and S. coagulans correctly in routine diagnostics. IMPORTANCE This study clearly shows that S. schleiferi is a concern in human hospital settings, whereas S. coagulans predominantly causes infections in animals. S. coagulans is more resistant to antibiotics and can sometimes transmit to humans via exposure to infected dogs. Even though genome-based methods can clearly differentiate the two species, current diagnostic methods used routinely in clinical microbiology laboratories cannot distinguish the two bacterial species.

Addressing the Clinical Feasibility of Adopting Circulating miRNA for Breast Cancer Detection, Monitoring and Management with Artificial Intelligence and Machine Learning Platforms.

Detecting breast cancer (BC) at the initial stages of progression has always been regarded as a lifesaving intervention. With modern technology, extensive studies have unraveled the complexity of BC, but the current standard practice of early breast cancer screening and clinical management of cancer progression is still heavily dependent on tissue biopsies, which are invasive and limited in capturing definitive cancer signatures for more comprehensive applications to improve outcomes in BC care and treatments. In recent years, reviews and studies have shown that liquid biopsies in the form of blood, containing free circulating and exosomal microRNAs (miRNAs), have become increasingly evident as a potential minimally invasive alternative to tissue biopsy or as a complement to biomarkers in assessing and classifying BC. As such, in this review, the potential of miRNAs as the key BC signatures in liquid biopsy are addressed, including the role of artificial intelligence (AI) and machine learning platforms (ML), in capitalizing on the big data of miRNA for a more comprehensive assessment of the cancer, leading to practical clinical utility in BC management.

Two Cases of Methimazole-Induced Agranulocytosis With Their Risk Factors.

Background: Antithyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of thyrotoxicosis. Agranulocytosis is a rare but lethal adverse effect of antithyroid medications. We have reported 2 cases of MMI-induced agranulocytosis with similar risk factors that likely predisposed them to this adverse reaction. Case Report: Case 1 involved a 71-year-old woman, with a history of Graves disease, who presented with an altered mental status. She was recently discharged on 40 mg of MMI twice daily, and she continued this dose for 2 months. She was readmitted and found to have neutropenic fever in the setting of MMI-induced agranulocytosis. MMI was discontinued, and she was started on filgrastim. Her cell counts gradually improved, and she was subsequently discharged.Case 2 involved a 68-year-old woman, with a history of Graves disease, who presented with severe back pain, nausea, and vomiting. She was recently discharged on 10 mg of MMI twice daily, which was increased to 10 mg 3 times a day. She was readmitted to the hospital because of a septic shock in the setting of pneumonia, colitis, bacteremia, and MMI-induced agranulocytosis. A bone marrow biopsy showed a polyclonal infiltrate with up to 85% plasma cells. Despite treatment with antibiotics, filgrastim, and continuous renal replacement therapy, she ultimately passed away. Discussion: Although these cases had differing outcomes, they shared similar features and risk factors, including older age, female sex, and relatively higher doses of MMI. Conclusion: Close follow up and awareness of risk factors, such as age, female sex, and higher doses of MMI, may decrease the risk of MMI-induced agranulocytosis and fatal outcomes.

Genomic Investigation of Two Acinetobacter baumannii Outbreaks in a Veterinary Intensive Care Unit in The Netherlands.

Acinetobacter baumannii is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended periods imposes a pressing public health threat. Two MDR A. baumannii outbreaks occurred in 2012 and 2014 in a companion animal intensive care unit (caICU) in the Netherlands. Whole-genome sequencing (WGS) was performed on dog clinical isolates (n = 6), environmental isolates (n = 5), and human reference strains (n = 3) to investigate if the isolates of the two outbreaks were related. All clinical isolates shared identical resistance phenotypes displaying multidrug resistance. Multi-locus Sequence Typing (MLST) revealed that all clinical isolates belonged to sequence type ST2. The core genome MLST (cgMLST) results confirmed that the isolates of the two outbreaks were not related. Comparative genome analysis showed that the outbreak isolates contained different gene contents, including mobile genetic elements associated with antimicrobial resistance genes (ARGs). The time-measured phylogenetic reconstruction revealed that the outbreak isolates diverged approximately 30 years before 2014. Our study shows the importance of WGS analyses combined with molecular clock investigations to reduce transmission of MDR A. baumannii infections in companion animal clinics.

High acceptability of HIV self-testing in a randomized trial among transgender women and men who have sex with men, Myanmar.

HIV self-testing (HIVST) shows promise to improve HIV diagnosis among those seeking privacy and anonymity in HIV testing. This may include sexual and gender diverse populations, who experience disproportionately high burdens of stigma and HIV globally. To inform potential scale-up of HIVST in Myanmar, we implemented a community-led, mixed-methods randomized trial in Yangon. Adult trans-feminine individuals and cisgender men who have sex with men were recruited via respondent-driven sampling. Participants (N = 577) completed a baseline survey and were randomized to community-based HIV testing services (HTS) or HIVST. One-third of participants reported lifetime HIV testing. Over half (59.4%) returned for a second study visit to report their test result and test acceptability, which was lower among HTS-assigned participants compared to those assigned to HIVST (55.6% vs. 63.1%; p = 0.096). Participants reported that both HIVST and HTS were easy to access, test, and interpret/understand the results of their HIV test. Ninety percent of HTS-assigned participants indicated they would test regularly if they could access HIVST. Qualitative participants (N = 20) described that the convenience and privacy afforded by HIVST may increase the availability and coverage of testing. Taken together, these results suggest HIVST is an acceptable, low-barrier complement to community-based HTS for key populations in Myanmar.

Is the stepping-down approach a better option than multiple daily injections in obese patients with poorly controlled Type 2 diabetes on advanced insulin therapy?

Aim: To determine whether de-escalating from advanced insulin therapy (AIT) to the combined use of metformin, an SGLT2 inhibitor, a GLP1 receptor agonist and basal insulin is the better option than multiple daily insulin injections (MDI) in obese patients with poorly controlled T2DM. Methods: This was a 16-week, prospective, randomized, controlled trial. Twenty-two obese patients with T2DM on AIT were randomized to intervention (step-down) or control (MDI) group. In the intervention group, all prandial insulin injections were discontinued, but the patient remained on basal insulin and metformin, to which an SGLT2i and a GLP1 RA were added. In the control group, the patient remained on MDI. Results: Compared to control group (n = 8), A1c was significantly lower at week 4 (9.54% vs 8.25%; p = .0088) and week 16 (9.7% vs 7.31%; p < .001) in intervention group (n = 10). In intervention group, compared to baseline, there was a significant decrease in weight (-16.38 pounds; p = .003), BMI (-3.06; p < .001), LDL cholesterol (-15.7 mg/dl; p = .0378), total cholesterol (-18.5 mg/dl; p = .0386), total daily insulin dose (-57.3 units; p < .001) and a significant improvement in DM-SAT patient satisfaction 0-100 scores: total score (+45.3; p < .001) and subscale scores (Convenience + 35.28, p = .019; Lifestyle + 35.8, p = .0052; Medical control + 51.3, p < .001; Wellbeing + 47.2, p = .0091) at week 16. Conclusion: De-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin in obese patients with poorly controlled T2DM on MDI resulted in significant improvement in glycaemic control, weight loss and significantly higher patient satisfaction. This stepping-down approach may be the better option than continuing MDI in these patients.

CCR5-edited CD4+ T cells augment HIV-specific immunity to enable post-rebound control of HIV replication.

BackgroundWe conducted a phase I clinical trial that infused CCR5 gene-edited CD4+ T cells to determine how these T cells can better enable HIV cure strategies.MethodsThe aim of trial was to develop RNA-based approaches to deliver zinc finger nuclease (ZFN), evaluate the effect of CCR5 gene-edited CD4+ T cells on the HIV-specific T cell response, test the ability of infused CCR5 gene-edited T cells to delay viral rebound during analytical treatment interruption, and determine whether individuals heterozygous for CCR5 Δ32 preferentially benefit. We enrolled 14 individuals living with HIV whose viral load was well controlled by antiretroviral therapy (ART). We measured the time to viral rebound after ART withdrawal, the persistence of CCR5-edited CD4+ T cells, and whether infusion of 10 billion CCR5-edited CD4+ T cells augmented the HIV-specific immune response.ResultsInfusion of the CD4+ T cells was well tolerated, with no serious adverse events. We observed a modest delay in the time to viral rebound relative to historical controls; however, 3 of the 14 individuals, 2 of whom were heterozygous for CCR5 Δ32, showed post-viral rebound control of viremia, before ultimately losing control of viral replication. Interestingly, only these individuals had substantial restoration of HIV-specific CD8+ T cell responses. We observed immune escape for 1 of these reinvigorated responses at viral recrudescence, illustrating a direct link between viral control and enhanced CD8+ T cell responses.ConclusionThese findings demonstrate how CCR5 gene-edited CD4+ T cell infusion could aid HIV cure strategies by augmenting preexisting HIV-specific immune responses.REGISTRATIONClinicalTrials.gov NCT02388594.FundingNIH funding (R01AI104400, UM1AI126620, U19AI149680, T32AI007632) was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). Sangamo Therapeutics also provided funding for these studies.

New Eocene primate from Myanmar shares dental characters with African Eocene crown anthropoids.

Recent discoveries of older and phylogenetically more primitive basal anthropoids in China and Myanmar, the eosimiiforms, support the hypothesis that Asia was the place of origins of anthropoids, rather than Africa. Similar taxa of eosimiiforms have been discovered in the late middle Eocene of Myanmar and North Africa, reflecting a colonization event that occurred during the middle Eocene. However, these eosimiiforms were probably not the closest ancestors of the African crown anthropoids. Here we describe a new primate from the middle Eocene of Myanmar that documents a new clade of Asian anthropoids. It possesses several dental characters found only among the African crown anthropoids and their nearest relatives, indicating that several of these characters have appeared within Asian clades before being recorded in Africa. This reinforces the hypothesis that the African colonization of anthropoids was the result of several dispersal events, and that it involved more derived taxa than eosimiiforms.

"We are not gays don't tell me those things": engaging 'hidden' men who have sex with men and transgender women in HIV prevention in Myanmar.

BACKGROUND: In Myanmar, HIV is concentrated among key populations, yet less than half of the estimated 250,000 men who have sex with men (MSM) and transgender women (TW) report recent HIV testing. As many as 50% of MSM and TW may conceal their same-sex preferences and behaviors, yet little is known about the barriers faced by those who are locally regarded as 'hidden' - that is, MSM who do not disclose same-sex preferences and/or identify as gay. This study explored specific barriers to accessing HIV testing and other prevention services among 'hidden' MSM to inform appropriate models of service delivery. METHODS: In-depth interviews with MSM (n = 12) and TW (n = 13) and focus group discussions (FGD) with MSM and TW community members, leaders and key informants (n = 35) were undertaken in Yangon during June - September 2015. Participants were recruited by word-of-mouth by trained peer data collectors. Responses to questions from semi-structured guides were transcribed and coded using Atlas Ti. Codes were based on key domains in the guides and applied to transcripts to identify and analyze emerging themes. RESULTS: Fear of stigma and discrimination and the need to meet gender expectations were key reasons for non-disclosure of same-sex preferences and behaviors; this typically manifested as avoidance of other MSM and settings in which sexual identity might be implicated. These concerns influenced preference and interaction with HIV services, with many avoiding MSM-specific services or eschewing HIV testing services entirely. The difficulties of engaging hidden MSM in HIV prevention was strongly corroborated by service providers. CONCLUSION: Hidden MSM face multiple barriers to HIV testing and prevention. Strategies cognizant of concerns for anonymity and privacy, such as One-Stop Shop services and online-based health promotion, can discretely provide services appropriate for hidden MSM. Enhanced capacity of peer-service providers and mainstream health staff to identify and respond to the psychosocial challenges reported by hidden MSM in this study may further encourage service engagement. Overarching strategies to strengthen the enabling environment, such as legal reform and LGBTI community mobilisation, can lessen stigma and discrimination and increase hidden MSM's comfort and willingness to discuss same-sex behavior and access appropriate services.

Lipid profiles and determinants of total cholesterol and hypercholesterolaemia among 25-74 year-old urban and rural citizens of the Yangon Region, Myanmar: a cross-sectional study.

OBJECTIVE: The first is to estimate the prevalence of dyslipidaemia (hypercholesterolaemia, hypertriglyceridaemia, high low-density lipoprotein (LDL) level and low high-density lipoprotein (HDL) level), as well as the mean levels of total cholesterol, triglyceride, LDL and HDL, in the urban and rural Yangon Region, Myanmar. The second is to investigate the association between urban-rural location and total cholesterol. DESIGN: Two cross-sectional studies using the WHO STEPS methodology. SETTING: Both the urban and rural areas of the Yangon Region, Myanmar. PARTICIPANTS: A total of 1370 men and women aged 25-74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded. RESULTS: Compared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001).Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women. CONCLUSION: The mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed.

A randomized clinical trial of vitamin D3 (cholecalciferol) in ulcerative colitis patients with hypovitaminosis D3.

AIM: To prospectively evaluate the effects of vitamin D3 on disease activity and quality of life in ulcerative colitis (UC) patients with hypovitaminosis D. METHODS: The study was a prospective double-blinded, randomized trial conducted at Community Regional Medical Center, Fresno, CA from 2012-2013. Patients with UC and a serum 25(OH)D level <30 ng/ml were eligible for the study. Enrolled subjects were randomized to receive either 2,000 IU or 4,000 IU of oral vitamin D3 daily for a total of 90 days. The Short IBD Questionnaire (SIBDQ) for quality of life, the Partial Mayo Score for UC disease activity and serum lab tests were compared between the two treatment groups. Matched pair t-tests were computed to assess differences between the vitamin D levels, CRP, UC disease activity and SIBDQ scores before and after vitamin D3 therapy using SPSS version 21. RESULTS: Eight UC patients received 2,000 IU/daily and ten UC patients received 4,000 IU/daily of vitamin D3 for 90 days. Vitamin D levels increased after 90 days of oral vitamin D3 in both dose groups. However, the increase in vitamin D levels after 90 days of oral vitamin D3, in the 4,000 IU group was significantly higher 16.80 ± 9.15 (p < 0.001) compared to the 2,000 IU group of vitamin D 5.00 ± 3.12 (p = 0.008). Normal vitamin D levels (>30 ng/dl) were achieved in four out of the ten UC patients (40%) in the 4,000 IU group and in one out of the eight UC patients (12%) in the 2,000 IU group. In the group receiving 4,000 IU/day of vitamin D3 the increase in quality life scores (SIBDQ) was significant 1.0 ± 1.0 (p = 0.017) but not in the 2,000 IU vitamin D3 group 0.1 ± 1.0 (p = 0.87). In the 2,000 IU of vitamin D3 group the mean decrease in the Partial Mayo UC Score was -0.5 ± 1.5 (p = 0.38) compared to -1.3 ± 2.9 (p = 0.19) in the 4,000 IU vitamin D3 group but this was not statistically significant. CRP levels decreased after 90 days of daily vitamin D3 in both the 2,000 IU group and 4,000 IU group by -3.0 ± 9.4 (p = 0.4) and -10.8 ± 35.0 (p = 0.36) respectively. CONCLUSION: Vitamin D3 at 4,000 IU/day is more effective than 2,000 IU/day in increasing vitamin D to sufficient levels in UC patients with hypovitaminosis D, however higher doses or treatment beyond ninety days may be required. Vitamin D3 may improve the quality of life in UC patients but clinically significant improvement is not yet established. The effect of vitamin D3 on UC disease activity is still unclear. Further larger studies are needed to investigate the effects of vitamin D in ulcerative colitis.

The Parasol Protocol: An Implementation Science Study of HIV Continuum of Care Interventions for Gay Men and Transgender Women in Burma/Myanmar.

BACKGROUND: Efforts to improve HIV diagnosis and antiretroviral therapy (ART) initiation among people living with HIV and reduce onward transmission of HIV rely on innovative interventions along multiple steps of the HIV care continuum. These innovative methods are particularly important for key populations, including men who have sex with men (MSM) and transgender women (TW). The HIV epidemic in Myanmar is concentrated among key populations, and national efforts now focus on reducing stigma and improving engagement of MSM and TW in HIV prevention and care. OBJECTIVE: This study aims to test the use of several innovations to address losses in the HIV care continuum: (1) use of respondent-driven sampling (RDS) to reach and engage MSM and TW in HIV testing, (2) HIV self-testing (HIVST) to increase HIV testing uptake and aid early diagnosis of infection, (3) community-based CD4 point-of-care (POC) technology to rapidly stage HIV disease for those who are HIV infected, and (4) peer navigation support to increase successful health system navigation for HIV-infected MSM and TW in need of ART or HIV engagement in care. METHODS: To assess the effect of HIVST, we will implement a randomized trial in which MSM and TW adults in the greater Yangon metropolitan area who are HIV uninfected will be recruited via RDS (N=366). Participants will complete a baseline socio-behavioral survey and will be randomized to standard, voluntary counseling and testing (VCT) or to HIVST. Biologic specimens will be collected during this baseline visit for confirmatory testing using dried blood spots. Participants will be asked to return to the study office to complete a second study visit in which they will report their HIV test result and answer questions on the acceptability of the assigned testing method. Aim 1 participants with confirmed HIV infection and who are not engaged in care (N=49) will be offered direct enrollment into Aims 2 and 3, which include immediate CD4 POC and the option for peer navigation, respectively. Aims 2 and 3 participants will be prospectively followed for 12 months with data collection including interviewer-administered sociobehavioral survey, CD4 POC, and viral load testing occurring biannually. Participants who accept peer navigation will be compared to those who decline peer navigation. Analyses will estimate the impact of CD4 POC on engagement in care and the impact of peer navigation on ART adherence and viral load. RESULTS: Formative qualitative research was conducted in June and September 2015 and led to further refinement of recruitment methods, HIVST instructions and counseling, and peer navigation methods. Aim 1 recruitment began in November 2015 with subsequent enrollment into Aims 2 and 3 and is currently ongoing. CONCLUSIONS: These innovative interventions may resolve gaps in the HIV care continuum among MSM and TW and future implementation may aid in curbing the HIV epidemic among MSM and TW in Myanmar.

New HIV testing technologies in the context of a concentrated epidemic and evolving HIV prevention: qualitative research on HIV self-testing among men who have sex with men and transgender women in Yangon, Myanmar.

INTRODUCTION: Global effort to increase early diagnosis and engagement in HIV care emphasize the importance of developing novel approaches to reaching those missed by traditional methods. Such needs are particularly great for men who have sex with men (MSM), transgender women (TW), and other populations who face stigma. Myanmar's HIV epidemic is concentrated among key populations and the revised National Strategy aims to reduce late diagnosis and barriers to care to curb HIV incidence among these groups. HIV self-testing (HIVST) may be one method to improve testing and diagnosis among key populations, by placing HIV testing and disclosure within the individual's control. METHODS: Formative, qualitative research including in-depth interviews with adult MSM (N = 12) and TW (N = 13) and focus group discussions with MSM, TW, and community key informants (N = 35) were conducted in June-September 2015 in Yangon, Myanmar. To inform a subsequent HIV care continuum intervention, including HIVST, participants' opinions and perceptions about HIVST were elicited. RESULTS: The confidentiality and privacy of HIVST, particularly as it related to disclosure of HIV status and sexual behaviour, was widely recognized among participants. These major advantages were further supported by the opportunity to avoid stigma, convenience of self-testing (reduced need for transportation and time to go to clinics), and the availability of a pain-free testing option. Participants weighed these benefits against perceived disadvantages of HIVST, the majority of which centred on the perception that HIVST does not include counselling. Participants were concerned that potential lack of counselling would result in poor mental health outcomes, inadequate linkage to HIV care and surveillance, and reductions in disclosure of HIV status. Participants did not view these disadvantages as an impediment, but provided suggestions for future implementation of HIVST in Myanmar. CONCLUSION: MSM and TW are optimistic about the confidentiality and privacy afforded by HIVST but wanted HIV counselling and linkage to appropriate services. The domestic reprioritization of HIV and opening of the country to international support has substantially increased the availability of HIV treatment and provides new opportunities, like HIVST, to potentially improve the HIV response for key populations who are at risk for HIV acquisition.

Impact of EMPA-REG OUTCOME® on the management of type 2 diabetes mellitus: a review for primary care physicians.

Cardiovascular (CV) disease is the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Most published trials of glucose-lowering agents have shown no significant CV benefit or increased risk of death or heart failure, with the exception of metformin. Three novel classes of glucose-lowering agents, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors, have been approved by the U.S. Food and Drug Administration for the treatment of T2DM in the United States and have also been available in other parts of the world in the past decade. Of the SGLT2 inhibitors, empagliflozin has demonstrated a CV benefit in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME®) while trials with other SGLT2 inhibitors are still ongoing. Empagliflozin has also provided possible renal protective benefit in those with mild-to-moderate renal impairment. The mechanisms behind the benefits seen with empagliflozin are likely multifactorial. Empagliflozin is the reasonable choice for add-on therapy in patients with long-standing T2DM who are at high CV risk as demonstrated in the EMPA-REG OUTCOME® study.

Retention and mortality outcomes from a community-supported public-private HIV treatment programme in Myanmar.

INTRODUCTION: There is a growing interest in the potential contribution the private sector can make towards increasing access to antiretroviral therapy (ART) in low- and middle-income settings. This article describes a public-private partnership that was developed to expand HIV care capacity in Yangon, Myanmar. The partnership was between private sector general practitioners (GPs) and a community-based non-governmental organization (International HIV/AIDS Alliance). METHODS: Retrospective analysis of 2119 patient records dating from March 2009 to April 2015 was conducted. Outcomes assessed were immunological response, loss to follow-up, all-cause mortality, and alive and retained in care. Follow-up time was calculated from the date of registration to the date of death, loss to follow-up, transfer out, or if still alive and known to be in care, until April 2015. Cox proportional hazards model was used to identify predictors of loss to follow-up and mortality. Kaplan-Meier survival analysis was used to estimate survival function of being alive and retained in care. RESULTS: The median number of patients for each of the 16 GPs was 42 (interquartile range (IQR): 25-227), and the median follow-up period was 13 months. The median patient age was 35 years (IQR: 30-41); 56.6% were men, 62 and 11.8% were in WHO Stage III and Stage IV at registration, respectively; median CD4 count at registration was 177 cells/mm3; and 90.7% were on ART in April 2015. The median CD4 count at registration increased from 122 cells/mm3 in 2009 to 194 cells/mm3 in 2014. Among patients on ART, CD4 counts increased from a median of 187 cells/mm3 at registration to 436 cells/mm3 at 36 months. The median time to initiation of ART among eligible patients was 29 days, with 93.8% of eligible patients being initiated on ART within 90 days. Overall, 3.3% patients were lost to follow-up, 4.2% transferred out to other health facilities, and 8.3% died during the follow-up period. Crude mortality rate was 48.6/1000 person-years; 42% (n=74) of deaths occurred during the pre-ART period and 39.8% (n=70) occurred during the first six months of ART. Of those who died during the pre-ART period, 94.5% were eligible for ART. In multivariate regression, baseline CD4 count and ART status were independent predictors of mortality, whereas ART status, younger age and patient volumes per provider were predictors of loss to follow-up. Probability of being alive and retained in care at six months was 96.8% among those on ART, 38.5% among pre-ART but eligible patients, and 20.0% among ART-ineligible patients. CONCLUSIONS: Effectively supported private sector GPs successfully administered and monitored ART in Myanmar, suggesting that community-supported private sector partnerships can contribute to expansion of HIV treatment and care capacity. To further improve patient outcomes, early testing and initiation of ART, combined with close clinical monitoring and support during the initial periods of enrolling in treatment and care, are required.

Cross-sectional descriptive study of management modalities and quality of life of surgical patients in a palliative care unit

Introduction: The goal of palliative care is the provision of the best quality of life (QOL) for terminally ill and dying patients. Advances in medical treatment has seen an increase in overall survival of all stages of malignant diseases. This includes advanced and/or inoperable malignancies where management is mainly palliative involving different modalities. Methods: We designed a cross-sectional descriptive study of surgical patients in a palliative care unit in a 1000-bedded teaching hospital in Kuantan, Malaysia. Objectives of this study are: to study the demographic characteristics and indications for admission of surgical patients in palliative care unit, to study the options of treatment modalities and their complications, to identify the barriers in decision making in surgical treatment and finally to objectively assess the quality of life of these patients by utilizing QUALITY OF LIFE (WHOQOL) –BREF –questionnaire. Results: One hundred and one eligible patients (53%) male, (47%) female of mean age of 54yrs, majority Malay and Chinese patients were included in the study. All patients had malignancies and they were Breast (30%), Lower gastrointestinal (GI) (24%), (18%) upper GI, (15%) hepato-biliary, and (7%) pancreatic cancers. Thirty two percents of patients had emergency treatment while the rest had supportive treatment. Barriers to decision making were mainly due to patient factors in 71%, while 12% was due to the disease presenting at an advanced stage and 15% due to limitation of care. The final results of overall quality of life rating were shown as poor (1%), neither poor nor good (42%), good (52%) and very good (2%). Conclusions: Palliative care and end of life decision making from surgical point of view is a delicate issue. Like all other fields in medicine, palliative care must be evidence-based with specific goal directed therapy. Our study shows that we are able to positively impact the quality of life in more than two thirds of our patients. Our aim is to achieve 100% success. As such, it is imperative to inculcate the goal of palliative care to all grades of health care personnel. ‘To cure sometimes, To relieve often, To comfort always’ should not be mere words.

Hypogonadism in chronic obstructive pulmonary disease: incidence and effects.

PURPOSE OF REVIEW: This review summarizes the literature on hypogonadism in men with chronic obstructive pulmonary disease (COPD). RECENT FINDINGS: COPD is a systemic disease with effects beyond the lungs. Many prior studies have shown that middle-aged and elderly COPD patients may develop hypogonadism. Prevalence of hypogonadism in men with COPD can range from 22 to 69% and has been associated with several other systemic manifestations including osteoporosis, depression, and muscle weakness. Recent studies have revealed conflicting results with regards to these previous perceptions. The discrepancies in the findings can be mainly attributed to small sample size, differences in patient selection, and inconsistent findings. Testosterone replacement therapy may result in modest improvements in fat-free mass and limb muscle strength but its therapeutic efficacy in COPD patients still remains controversial. SUMMARY: The relationship between hypogonadism and COPD still remains poorly understood. The current literature is at best circumstantial.

Clinical behavior of radiation-induced thyroid cancer: factors related to recurrence.

BACKGROUND: Whether thyroid cancer is more aggressive in radiation-exposed patients is not resolved. The frequency of aggressive features in post-Chernobyl patients suggests this may be the case. Our aim was to address this question by re-examining the pattern of risk factors for recurrence of thyroid cancers found in a cohort exposed to external radiation. METHODS: The study population was drawn from a cohort of 4296 people, followed since 1974, who were treated before the age of 16 with conventional external radiation for benign conditions of the head and neck between 1939 and the early 1960s. The study group consisted of 390 patients who had surgically verified thyroid cancer. Potential risk factors for recurrence were evaluated by proportional hazards analysis. RESULTS: Fifty patients had recurrences an average of 8.7 years after diagnosis while the other 340 patients were followed for an average of 19.7 years. The sooner after radiation exposure the cancer occurred, the more likely it was to recur (hazard ratio, 0.96/year; 95% confidence interval [CI] 0.91-0.99). Taking into account the effect of the onset of screening in 1974, the features predictive of recurrence were younger age at the initial diagnosis (hazard ratio, 0.95/year; 95% CI, 0.91-0.99) and the size of the thyroid cancer (hazard ratio, 1.2/cm; 95% CI, 1.0-1.6). CONCLUSION: Although not based on a direct comparison, we conclude that thyroid cancers following external radiation exposure are not, on average, more aggressive than other thyroid cancers. The similarity of risk factors for recurrence suggests that they should be treated and followed in the same way as non-radiation-induced thyroid cancers.