Rifampicin-resistant tuberculosis patients in Myanmar in 2016: how many are lost on the path to treatment?

SETTING: Regional tuberculosis (TB) centres of the Yangon and Mandalay Regions of Myanmar, which account for 65% of all notified rifampicin-resistant tuberculosis (RR-TB) cases countrywide. OBJECTIVE: To determine 1) initial loss to follow-up (LTFU), 2) treatment delay, and 3) factors associated with initial LTFU and treatment delay among RR-TB patients residing in the Yangon and Mandalay regions diagnosed using Xpert® during January-August 2016. DESIGN: This was a retrospective cohort study. Each diagnosed patient was tracked in the drug-resistant TB treatment registers of the Yangon and Mandalay regional treatment centres for January-December 2016 using patient name, age, sex, township and date of diagnosis. If the diagnosed patient was not found in the treatment register by 31 December 2016, he/she was considered 'initial LTFU'. RESULTS: Of the 1037 RR-TB patients diagnosed, 310 (30%) experienced initial LTFU, which was significantly higher among patients aged 55 years and among those diagnosed in the Mandalay Region. A treatment delay of >1 month was observed in 440 (70%) patients (median delay 41 days). Delay was uniformly high across patient subgroups, and was not associated with any factor. CONCLUSION: Initial LTFU and treatment delays among RR-TB patients were high. Future studies using qualitative research methods are needed to ascertain the reasons for this observation.

Comparing breast-reduction techniques: time-to-event analysis and recommendations.

BACKGROUND: Breast reduction is a common procedure used to improve physical and aesthetic factors associated with breast hypertrophy. This study investigated how surgical technique alone affects the risk factors for complications and profiled differences between techniques. Complications were assessed by the use of time-to-event methods. METHODS: Patient information was extracted from a cohort of 283 patients. Demographic, surgical, and follow-up information was analyzed for patients undergoing surgical procedures using the inferior pedicle Wise pattern (IPWP) and modified Hall-Findlay (MHF) techniques. The patients managed with the IPWP technique were considered control subjects. The failure rates were described using the Kaplan-Meier failure estimator to provide a true estimate of the experienced complication rates. RESULTS: Overall, few differences were noted between the groups except for total tissue removed. The overall failure (complication) rate at 6 months was 18.8%, with 9% of all the patients experiencing a major complication that required operative intervention/revision. As expected, the period with the greatest risk of complication was the first month after surgery. Surgical technique, total tissue removed, and age were nonpredictive of complications. Overall, the IPWP group had significantly more total tissue removed than the MHF group (median difference, 227 g; P=0.002). There was no evidence of a learning curve when an experienced surgeon moved from the one technique to the other. CONCLUSION: At 6 months after surgery, 19% of patients are expected to have experienced a complication. There appears to be few differences in outcomes between the techniques of breast reductions used, and the success or otherwise almost certainly relates to factors independent of surgical technique and includes patient selection, operative skill, and experience. Time-to-event analysis provides a precise assessment and description of the complication profile. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

Preliminary study of osmotic membrane bioreactor: effects of draw solution on water flux and air scouring on fouling.

Preliminary study on a novel osmotic membrane bioreactor (OMBR) was explored. Objective of this study was to investigate the effects of draw solution on membrane flux and air scouring at the feed side on fouling tendency in a pilot OMBR system composing the anoxic/aerobic and forward osmosis (FO) processes. Domestic sewage was the raw feed, FO membrane from HTI and NaCl/MgSO4 draw solutions were used in the experiments. Fluxes of 3 l/m2/h (LMH) and 7.2 LMH were achieved at osmotic pressure of 5 and 22.4 atm, respectively. No significant flux decline was observed at 3 LMH over 190 h and at 7.2 LMH over 150 h when air scouring was provided at the feed side of the membrane. However, without air scouring, the flux at 22.4 atm osmotic pressure declined by 30% after 195 h and then levelled off. The potential advantages of the fouling reversibility with air scouring under the operating conditions of the pilot OMBR and better water quality in OMBR over the conventional MBR were preliminarily demonstrated.

Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidism: a sequential comparison.

Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P: < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting that intravenous 1alphaD(2) therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.

Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism.

Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.

Calcimimetic agents and the calcium-sensing receptor.

Blood ionized extracellular calcium is closely regulated. To accomplish this, a hormone-like receptor that is responsive to extracellular ionized calcium regulates both the secretion of parathyroid hormone and the excretion of urinary calcium (as well as other cellular processes). Several hereditary disorders have mutations that cause either loss or gain of function of the calcium-sensing receptor, and alterations of the calcium-sensing receptor may play a role in both primary and secondary hyperparathyroidism. Calcimimetics are agents that act to make the calcium-sensing receptor more sensitive to extracellular ionized calcium; thereby they suppress the secretion of parathyroid hormone. Early trials in animal models of secondary hyperparathyroidism and in patients with primary hyperparathyroidism or with uremic secondary hyperparathyroidism have shown that the first generation calcimimetic, R-568, effectively lowers parathyroid hormone levels and is well tolerated.