Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

Results of a novel intervention to increase rates of diagnosis and treatment of primary hyperparathyroidism.

BACKGROUND: Veterans with primary hyperparathyroidism are under diagnosed and undertreated. We report the results of a pilot study to address this problem. METHODS: We implemented a stakeholder-driven, multi-component intervention to increase rates of diagnosis and treatment for primary hyperparathyroidism at a single VA hospital. Intervention effects were evaluated using an interrupted time series analysis. RESULTS: The mean age of Veterans affected by the intervention was 67 years (SD 12.1) and 84 â€‹% were men. Compared to the pre-intervention period, the intervention doubled the proportion of Veterans who were appropriately evaluated for hyperparathyroidism (absolute difference 25 â€‹%, 95 â€‹% CI 11 â€‹%-38 â€‹%, p â€‹< â€‹0.001) and increased referrals for treatment by 27 â€‹% (95 â€‹% CI 7 â€‹%-47 â€‹%, p â€‹< â€‹0.012). CONCLUSION: Our pilot study suggests it is feasible to address the underdiagnosis and undertreatment of primary hyperparathyroidism among Veterans.

The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

Feminizing gender-affirming hormone therapy (GAHT) is the mainstay of treatment for many transgender and gender diverse (TGD) people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in TGD adults on feminizing GAHT. We also report on testosterone suppression, route (i.e., subcutaneous vs. intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. The data we reviewed suggests that the current guidelines, which recommend starting doses 2-10 mg weekly or 5-30 mg every two weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol valerate via subcutaneous or intramuscular injections at a dose ≤ 5 mg weekly and then titrate accordingly to keep levels within guideline recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

Nonsense-mediated mRNA decay affects hyperactive root formation in oculo-facio-cardio-dental syndrome via up-frameshift protein 1.

OBJECTIVES: Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked genetic disorder caused by mutations in the BCL6 co-repressor (BCOR) and is mainly characterized by radiculomegaly (elongated dental roots). All BCOR mutations reported to date have been associated with premature termination codons, indicating that nonsense-mediated mRNA decay (NMD) might play a vital role in the pathogenesis of OFCD syndrome. However, the molecular mechanisms underlying NMD remain unclear. In this study, we investigated the involvement of up-frameshift protein 1 (UPF1), which plays a central role in NMD, in the hyperactive root formation caused by BCOR mutations. METHODS: Periodontal ligament cells, isolated from a Japanese woman with a c.3668delC frameshift mutation in BCOR, and primary human periodontal ligament fibroblasts (HPdLFs) were used for an RNA immunoprecipitation assay to confirm the binding of UPF1 to mutated BCOR. Additionally, the effects of UPF1 on the BCOR transcription levels and corresponding gene expression were determined by performing relative quantitative real-time polymerase chain reactions. RESULTS: RNA immunoprecipitation revealed that UPF1 binds to exon 9 of mutated BCOR. Additionally, UPF1 knockdown via siRNA upregulated the transcription of BCOR, whereas overexpression of wild-type and mutated BCOR with the same frameshift mutation in HPdLFs altered bone morphogenetic protein 2 (BMP2) expression. CONCLUSIONS: Our findings indicate that BCOR mutations regulate the transcription of BCOR via UPF1, which may in turn regulate the expression of BMP2. NMD, caused by a c.3668delC mutation, potentially leads to an OFCD syndrome phenotype, including elongated dental roots.

What Is the Evidence Surrounding the Cost-Effectiveness of Osteobiologic Use in ACDF Surgery? A Systematic Review of the Literature.

STUDY DESIGN: This study constitutes a systematic review of the literature. OBJECTIVE: The aim of this study was to identify and present all available studies that report on the costs of osteobiologics used in anterior cervical discectomy and fusion (ACDF). METHODS: The literature was systematically reviewed to identify studies with specific inclusion criteria: (1) randomized controlled trials and observational studies, (2) in adult patients, (3) with herniated disc(s) or degenerative cervical spine disease, (4) reporting on either direct or indirect costs of using specific osteobiologics in an ACDF operation. (5) Only studies in English were included. The quality of the included studies was assessed using the MINORS and RoB 2.0 tools. RESULTS: Overall, 14 articles were included; one randomized controlled trial and 13 observational studies. The most commonly used osteobiologics other than autograft/iliac crest bone graft (ICBG) were allograft and bone morphogenetic protein (BMP). None of the studies was reported to be industry-supported. There was considerable heterogeneity on the reported costs. Overall, most studies reported on surgery-related costs, such as anesthesia, operating room, surgical materials and surgeon's fee. Only two studies, both using allograft, reported the exact cost of the osteobiologic used (450 GBP, $700). Some of the studies reported on the cost of care during hospitalization for the surgical operation, such as radiology studies, emergency room costs, cardiologic evaluation, laboratory studies, pharmacy costs, and room costs. Only a few studies reported on the cost of follow-up, reoperation, and physical therapy and rehabilitation. CONCLUSION: Based on the data of this current systematic review, no recommendations can be made regarding the cost-effectiveness of using osteobiologics in ACDF. Given the high costs of osteobiologics, this remains a topic of importance. The design of future studies on the subject should include cost effectiveness.

The Hemoglobin Wayne Variant and Association With Falsely Elevated HbA1c.

The objective of this work is to explain the effect of the clinically silent hemoglobinopathy hemoglobin Wayne (Hb Wayne) variant on glycated hemoglobin A1c (HbA1c) assay. This variant can result in falsely high HbA1c values among euglycemic individuals without diabetes mellitus (DM). We discuss 3 patients who were diagnosed with type 2 DM based on spuriously high HbA1c values due to the presence of Hb Wayne. All 3 patients were found to have elevated HbA1c values that did not correlate with other glycemic parameters such as capillary blood sugar, 2-hour oral glucose tolerance test, and fructosamine levels. Hemoglobin electrophoresis revealed that each patient had a rare hemoglobinopathy called Hb Wayne variant. These patients were reassured that they did not have DM and were able to avoid unnecessary treatment. These cases emphasize the importance of clinical judgment in recognizing the limitations and caveats of the HbA1c test. It is always necessary to investigate further any discordance between HbA1c values and the clinical picture or other glycemic parameters.

Molecular mechanism of hyperactive tooth root formation in oculo-facio-cardio-dental syndrome.

Mutations in the B-cell lymphoma 6 (BCL6) interacting corepressor (BCOR) cause oculo-facio-cardio-dental (OFCD) syndrome, a rare X-linked dominant condition that includes dental radiculomegaly among other characteristics. BCOR regulates downstream genes via BCL6 as a transcriptional corepressor. However, the molecular mechanism underlying the occurrence of radiculomegaly is still unknown. Thus, this study was aimed at identifying BCOR-regulated genetic pathways in radiculomegaly. The microarray profile of affected tissues revealed that the gene-specific transcriptional factors group, wherein nucleus factor 1B, distal-less homeobox 5, and zinc finger protein multitype 2 (ZFPM2) were the most upregulated, was significantly expressed in periodontal ligament (PDL) cells of the diseased patient with a frameshift mutation (c.3668delC) in BCOR. Wild-type BCOR overexpression in human periodontal ligament fibroblasts cells significantly hampered cellular proliferation and ZFPM2 mRNA downregulation. Promoter binding assays showed that wild-type BCOR was recruited in the BCL6 binding of the ZFPM2 promoter region after immunoprecipitation, while mutant BCOR, which was the same genotype as of our patient, failed to recruit these promoter regions. Knockdown of ZFPM2 expression in mutant PDL cells significantly reduced cellular proliferation as well as mRNA expression of alkaline phosphatase, an important marker of odontoblasts and cementoblasts. Collectively, our findings suggest that BCOR mutation-induced ZFPM2 regulation via BCL6 possibly contributes to hyperactive root formation in OFCD syndrome. Clinical data from patients with rare genetic diseases may aid in furthering the understanding of the mechanism controlling the final root length.

The cost of community outreach HIV interventions: a case study in Thailand.

BACKGROUND: There was an estimated 440,000 people living with HIV in Thailand in 2018. New cases are declining rapidly thanks to successful prevention programs and scaling up of anti-retroviral therapy (ART). Thailand aims to achieve its commitment to end the HIV epidemic by 2030 and implemented a cascade of HIV interventions through the Reach-Recruit-Test-Treat-Retain (RRTTR) program. METHODS: This study focused on community outreach HIV interventions implemented by Non-Governmental Organizations (NGOs) under the RRTTR program in 27 provinces. We calculated unit cost per person reached for HIV interventions targeted at key-affected populations (KAPs) including men who have sex with men/ transgender (MSM/TG), male sex workers (MSW), female sex workers (FSW), people who inject drugs (PWID) and migrants (MW). We studied program key outputs, costs, and unit costs in variations across different HIV interventions and geographic locations in Thailand. We used these estimates to determine costs of HIV interventions and evaluate economies of scale. RESULTS: The interventions for migrants in Samut Sakhon was the least costly with a unit cost of 21.6 USD per person to receive services, followed by interventions for migrants in Samut Prakan 23.2 USD per person reached, MSM/TG in Pratum Thani 26.5USD per person reached, MSM/TG in Nonthaburi 26.6 USD per person reached and, MSM/TG in Chon Buri with 26.7 USD per person. The interventions yielded higher efficiency in large metropolitan and surrounding provinces. Harm reduction programs were the costliest compare with other interventions. There was association between unit cost and scale of among interventions indicating the presence of economies scale. Implementing HIV and TB interventions jointly increased efficiency for both cases. CONCLUSION: This study suggested that unit cost of community outreach HIV and TB interventions led by CSOs will decrease as they are scaled up. Further studies are suggested to follow up with these ongoing interventions for identifying potential contextual factors to improve efficiency of HIV prevention services in Thailand.

Sliding with the sines - fatal hyperkalemia: A case report.

BACKGROUND: Classic electrocardiographic manifestations of hyperkalemia starting with peaked symmetrical T-waves are widely recognized in daily clinical practice but little evidence is documented how quickly it can evolve in real-time. CASE SUMMARY: An elderly diabetic and hypertensive male presented with acute renal failure and rhabdomyolysis. He experienced cardiac arrest with moderate hyperkalemia despite medical treatment and hemodialysis. Telemetry changes were retrospectively studied and found to have significant rhythm changes that occurred just less than 10 minutes prior to the cardiac arrest. CONCLUSION: In hyperkalemia, telemetry rhythm can change instantaneously in a significant way. Rapidly rising potassium could be life threatening and may require more than medical treatment.

Mass drug administration for the acceleration of malaria elimination in a region of Myanmar with artemisinin-resistant falciparum malaria: a cluster-randomised trial.

BACKGROUND: To contain multidrug-resistant Plasmodium falciparum, malaria elimination in the Greater Mekong subregion needs to be accelerated while current antimalarials remain effective. We evaluated the safety, effectiveness, and potential resistance selection of dihydroartemisinin-piperaquine mass drug administration (MDA) in a region with artemisinin resistance in Myanmar. METHODS: We did a cluster-randomised controlled trial in rural community clusters in Kayin (Karen) state in southeast Myanmar. Malaria prevalence was assessed using ultrasensitive quantitative PCR (uPCR) in villages that were operationally suitable for MDA (villages with community willingness, no other malaria control campaigns, and a population of 50-1200). Villages were eligible to participate if the prevalence of malaria (all species) in adults was greater than 30% or P falciparum prevalence was greater than 10% (or both). Contiguous villages were combined into clusters. Eligible clusters were paired based on P falciparum prevalence (estimates within 10%) and proximity. Community health workers provided routine malaria case management and distributed long-lasting insecticidal bed-nets (LLINs) in all clusters. Randomisation of clusters (1:1) to the MDA intervention group or control group was by public coin-flip. Group allocations were not concealed. Three MDA rounds (3 days of supervised dihydroartemisinin-piperaquine [target total dose 7 mg/kg dihydroartemisinin and 55 mg/kg piperaquine] and single low-dose primaquine [target dose 0·25 mg base per kg]) were delivered to intervention clusters. Parasitaemia prevalence was assessed at 3, 5, 10, 15, 21, 27, and 33 months. The primary outcomes were P falciparum prevalence at months 3 and 10. All clusters were included in the primary analysis. Adverse events were monitored from the first MDA dose until 1 month after the final dose, or until resolution of any adverse event occurring during follow-up. This trial is registered with ClinicalTrials.gov, NCT01872702. FINDINGS: Baseline uPCR malaria surveys were done in January, 2015, in 43 villages that were operationally suitable for MDA (2671 individuals). 18 villages met the eligibility criteria. Three villages in close proximity were combined into one cluster because a border between them could not be defined. This gave a total of 16 clusters in eight pairs. In the intervention clusters, MDA was delivered from March 4 to March 17, from March 30 to April 10, and from April 27 to May 10, 2015. The weighted mean absolute difference in P falciparum prevalence in the MDA group relative to the control group was -10·6% (95% CI -15·1 to -6·1; p=0·0008) at month 3 and -4·5% (-10·9 to 1·9; p=0·14) at month 10. At month 3, the weighted P falciparum prevalence was 1·4% (0·6 to 3·6; 12 of 747) in the MDA group and 10·6% (7·0 to 15·6; 56 of 485) in the control group. Corresponding prevalences at month 10 were 3·2% (1·5 to 6·8; 34 of 1013) and 5·8% (2·5 to 12·9; 33 of 515). Adverse events were reported for 151 (3·6%) of 4173 treated individuals. The most common adverse events were dizziness (n=109) and rash or itching (n=20). No treatment-related deaths occurred. INTERPRETATION: In this low-transmission setting, the substantial reduction in P falciparum prevalence resulting from support of community case management was accelerated by MDA. In addition to supporting community health worker case management and LLIN distribution, malaria elimination programmes should consider using MDA to reduce P falciparum prevalence rapidly in foci of higher transmission. FUNDING: The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Case Report: Children with Severe Nutritional Rickets in the Naga Region in Northwest Myanmar, on the border with India.

Rickets is an often-neglected, painful, and disabling childhood condition of impaired bone mineralization. In this case series we describe a cluster of 29 children with severe, painful bone deformities who live in the very remote region of Nagaland in northwest Myanmar. Children were found to have low 25-hydroxyvitamin D, elevated parathyroid hormone, and elevated alkaline phosphatase levels, consistent with nutritional rickets secondary to vitamin D deficiency, calcium deficiency, or a combination of the two. After treatment with vitamin D3 and calcium carbonate, significant improvement was seen in symptoms, biochemistry, and radiography. This is the first report of nutritional rickets in Myanmar in more than 120 years. Vitamin D and calcium supplementation, and food fortification for pregnant women and young children may be required to prevent this potentially devastating disease.

Geographical distribution of Burkholderia pseudomallei in soil in Myanmar.

BACKGROUND: Burkholderia pseudomallei is a Gram-negative bacterium found in soil and water in many tropical countries. It causes melioidosis, a potentially fatal infection first described in 1911 in Myanmar. Melioidosis is a common cause of sepsis and death in South and South-east Asia, but it is rarely diagnosed in Myanmar. We conducted a nationwide soil study to identify areas where B. pseudomallei is present. METHODOLOGY/PRINCIPAL FINDINGS: We collected soil samples from 387 locations in all 15 states and regions of Myanmar between September 2017 and June 2019. At each site, three samples were taken at each of three different depths (30, 60 and 90 cm) and were cultured for B. pseudomallei separately, along with a pooled sample from each site (i.e. 10 cultures per site). We used a negative binomial regression model to assess associations between isolation of B. pseudomallei and environmental factors (season, soil depth, soil type, land use and climate zones). B. pseudomallei was isolated in 7 of 15 states and regions. Of the 387 sites, 31 (8%) had one or more positive samples and of the 3,870 samples cultured, 103 (2.7%) tested positive for B. pseudomallei. B. pseudomallei was isolated more frequently during the monsoon season [RR-2.28 (95% CI: 0.70-7.38)] and less in the hot dry season [RR-0.70 (95% CI: 0.19-2.56)] compared to the cool dry season, and in the tropical monsoon climate zone [RR-2.26; 95% CI (0.21-6.21)] compared to the tropical dry winter climate zone. However, these associations were not statistically significant. B. pseudomallei was detected at all three depths and from various soil types (clay, silt and sand). Isolation was higher in agricultural land (2.2%), pasture land (8.5%) and disused land (5.8%) than in residential land (0.4%), but these differences were also not significant. CONCLUSION/SIGNIFICANCE: This study confirms a widespread distribution of B. pseudomallei in Myanmar. Clinical studies should follow to obtain a better picture of the burden of melioidosis in Myanmar.

Bacterial Profile and Antibiotic Resistance among Cancer Patients with Urinary Tract Infection in a National Tertiary Cancer Hospital of Nepal.

Cancer patients are at high risk of antibiotic resistant bacterial urinary tract infections (UTIs). In this study, we assessed the bacterial profile and antibiotic resistance among cancer patients suspected of UTI in B.P. Koirala Memorial Cancer Hospital in Nepal through a cross-sectional study with routinely collected data. All cancer patients who had a recorded urine culture between July 2018-June 2019 were included in the study. Out of 308 patients who had undergone culture, 73 (24%) of samples had bacterial growth. The most common organisms isolated were E. coli (58%), Staphylococcus (11%) and Klebsiella (10%). These bacteria had undergone susceptibility testing to 27 different antibiotics in various proportions. Of the limited antibiotic testing levels, nitrofurantoin (54/66, 82%) and amikacin (30/51, 59%) were the most common. Among those tested, there were high levels of resistance to antibiotics in the "Access" and "Watch" groups of antibiotics (2019 WHO classification). In the "Reserve" group, both antibiotics showed resistance (polymyxin 15%, tigecycline 8%). Multidrug resistance was seen among 89% of the positive culture samples. This calls for urgent measures to optimize the use of antibiotics in UTI care at policy and health facility levels through stewardship to prevent further augmentation of antibiotic resistance among cancer patients.

Observational study of adult respiratory infections in primary care clinics in Myanmar: understanding the burden of melioidosis, tuberculosis and other infections not covered by empirical treatment regimes.

BACKGROUND: Lower respiratory infections constitute a major disease burden worldwide. Treatment is usually empiric and targeted towards typical bacterial pathogens. Understanding the prevalence of pathogens not covered by empirical treatment is important to improve diagnostic and treatment algorithms. METHODS: A prospective observational study in peri-urban communities of Yangon, Myanmar was conducted between July 2018 and April 2019. Sputum specimens of 299 adults presenting with fever and productive cough were tested for Mycobacterium tuberculosis (microscopy and GeneXpert MTB/RIF [Mycobacterium tuberculosis/resistance to rifampicin]) and Burkholderia pseudomallei (Active Melioidosis Detect Lateral Flow Assay and culture). Nasopharyngeal swabs underwent respiratory virus (influenza A, B, respiratory syncytial virus) polymerase chain reaction testing. RESULTS: Among 299 patients, 32% (95% confidence interval [CI] 26 to 37) were diagnosed with tuberculosis (TB), including 9 rifampicin-resistant cases. TB patients presented with a longer duration of fever (median 14 d) and productive cough (median 30 d) than non-TB patients (median fever duration 6 d, cough 7 d). One case of melioidosis pneumonia was detected by rapid test and confirmed by culture. Respiratory viruses were detected in 16% (95% CI 12 to 21) of patients. CONCLUSIONS: TB was very common in this population, suggesting that microscopy and GeneXpert MTB/RIF on all sputum samples should be routinely included in diagnostic algorithms for fever and cough. Melioidosis was uncommon in this population.

Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma.

In Myanmar, hepatocellular carcinoma (HCC) is commonly seen in young adult and associated with poor prognosis, while the molecular mechanisms that characterize HCC in Myanmar are unknown. As co-activation of Wnt/ß-catenin signaling and c-Myc (Myc) are reported to associate with malignancy of HCC, we immunohistochemically investigated the expression of Pygo2 and Bcl9, the co-activators of the Wnt/ß-catenin signaling, Myc and PCNA in 60 cases of Myanmar HCC. Pygo2 expression was confirmed by in situ hybridization. The signal intensity was measured by image analyzer and then statistically analyzed. As a result, the expression of Pygo2 was significantly higher in HCC compared to normal liver tissue and the nuclear signal was the most intense in poorly differentiated HCC. Cytoplasmic Bcl9 was expressed in the normal liver tissue but decreased in HCC with the progression of histopathological grade. Myc was significantly higher in poorly differentiated HCC, whereas PCNA labeling index increased with the progression of histopathological grade. Nuclear Pygo2 showed strong correlation with nuclear Myc (P < 0.01) and PCNA (P < 0.001), and inversely correlated with cytoplasmic Bcl9 (P < 0.01). Our results suggested Wnt/ß-catenin and Myc signaling is commonly activated in Myanmar HCC and that the correlative upregulation of nuclear Pygo2 and Myc characterizes the malignant features of HCC in Myanmar.

Serological evidence indicates widespread distribution of rickettsioses in Myanmar.

BACKGROUND: Little research has been published on the prevalence of rickettsial infections in Myanmar. This study determined the seroprevalence of immunoglobulin G (IgG) antibodies to rickettsial species in different regions of Myanmar. METHODS: Seven hundred leftover blood samples from patients of all ages in primary care clinics and hospitals in seven regions of Myanmar were collected. Samples were screened for scrub typhus group (STG), typhus group (TG) and spotted fever group (SFG) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Immunofluorescence assays were performed for the same rickettsial groups to confirm seropositivity if ELISA optical density ≥0.5. RESULTS: Overall IgG seroprevalence was 19% [95% confidence interval (CI) 16-22%] for STG, 5% (95% CI 3-7%) for TG and 3% (95% CI: 2-5%) for SFG. The seroprevalence of STG was particularly high in northern and central Myanmar (59% and 19-33%, respectively). Increasing age was associated with higher odds of STG and TG seropositivity [per 10-year increase, adjusted odds ratio estimate 1.68 (p < 0.01) and 1.24 (p = 0.03), respectively]. CONCLUSION: Rickettsial infections are widespread in Myanmar, with particularly high seroprevalence of STG IgG antibodies in central and northern regions. Healthcare workers should consider rickettsial infections as common causes of fever in Myanmar.

PSEUDOHYPOPHOSPHATEMIA IN A PATIENT WITH MULTIPLE MYELOMA.

OBJECTIVE: To discuss the diagnosis and management of paraprotein interference in the setting of multiple myeloma (MM). METHODS: We discuss the evaluation of hypophosphatemia in a patient with MM and present a review of the relevant literature. RESULTS: Our patient, who had a history of MM, was found to have persistently undetectable serum phosphate which did not respond to aggressive phosphate replacement. His clinical condition was not consistent with severe phosphate depletion and hence paraprotein interference secondary to MM was suspected. Re-analyzation of samples on a different machine showed normal serum inorganic phosphate levels. CONCLUSION: Paraprotein interference from MM causing pseudohypophosphatemia can be overlooked and lead to unnecessary treatment. Recognition of this phenomenon is important to all clinicians, especially in light of potential complications of unnecessary treatment.

Correction to: Accelerated proliferation of hepatocytes in rats with iron overload after partial hepatectomy.

The figure shown below is the correct version. We apologize for the mistake.

What Are the Barriers for Uptake of Antiretroviral Therapy in HIV-Infected Tuberculosis Patients? A Mixed-Methods Study from Ayeyawady Region, Myanmar.

Antiretroviral therapy (ART) coverage among HIV-infected tuberculosis (HIV-TB) patients has been suboptimal in Myanmar and the reasons are unknown. We aimed to assess the ART uptake among HIV-TB patients in public health facilities of Ayeyawady Region from July 2017-June 2018 and explore the barriers for non-initiation of ART. We conducted an explanatory mixed-methods study with a quantitative component (cohort analysis of secondary programme data) followed by a descriptive qualitative component (thematic analysis of in-depth interviews of 22 providers and five patients). Among 12,447 TB patients, 11,057 (89%) were HIV-tested and 627 (5.7%) were HIV-positive. Of 627 HIV-TB patients, 446 (71%) received ART during TB treatment (86 started on ART prior to TB treatment and rest started after TB treatment). Among the 181 patients not started on ART, 60 (33%) died and 41 (23%) were lost-to-follow-up. Patient-related barriers included geographic and economic constraints, poor awareness, denial of HIV status, and fear of adverse drug effects. The health system barriers included limited human resource, provision of ART on 'fixed' days only, weaknesses in counselling, referral and feedback mechanism, and clinicians' reluctance to start ART early due to concerns about immune reconstitution inflammatory syndrome. We urge the national TB and HIV programs to take immediate actions to improve the ART uptake.

OFF-LABEL USE AND MISUSE OF TESTOSTERONE, GROWTH HORMONE, THYROID HORMONE, AND ADRENAL SUPPLEMENTS: RISKS AND COSTS OF A GROWING PROBLEM.

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to "adrenal fatigue," an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.