Drug resistant TB - latest developments in epidemiology, diagnostics and management.

AIM: The aim of this review is to inform the reader on the latest developments in epidemiology, diagnostics and management. EPIDEMIOLOGY: Drug-resistant Tuberculosis (DR-TB) continues to be a current global health threat, and is defined by higher morbidity and mortality, sequelae, higher cost and complexity. The WHO classifies drug-resistant TB into 5 categories: isoniazid-resistant TB, rifampicin resistant (RR)-TB and MDR-TB, (TB resistant to isoniazid and rifampicin), pre-extensively drug-resistant TB (pre-XDR-TB) which is MDR-TB with resistance to a fluoroquinolone and finally XDR-TB that is TB resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). Of 500,000 estimated new cases of RR-TB in 2020, only 157 903 cases are notified. Only about a third of cases are detected and treated annually. DIAGNOSTICS: Recently newer rapid diagnostic methods like the GeneXpert, whole genome sequencing and Myc-TB offer solutions for rapid detection of resistance. TREATMENT: The availability of new TB drugs and shorter treatment regimens have been recommended for the management of DR-TB. CONCLUSION: Despite advances in diagnostics and treatments we still have to find and treat two thirds of the drug resistant cases that go undetected and therefore go untreated each year. Control of TB and elimination will only occur if cases are detected, diagnosed and treated promptly.

Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic.

The WHO 2020 global TB Report estimates that in 2019 there were an estimated 500,000 cases of multi-drug resistant TB (MDR-TB) of which only 186,772 MDR-TB cases were diagnosed, and positive treatment outcomes were achieved in 57% of them. These data highlight the need for accelerating and improving MDR-TB screening, diagnostic, treatment and patient follow-up services. The last decade has seen three new TB drugs being licensed; bedaquiline, delamanid and pretomanid, and combinations these new, existing and repurposed drugs are leading to improved cure rates. The all oral six month WHO regimen for MDR-TB is more tolerable, has higher treatment success rates and lower mortality. However, the unprecedented ongoing COVID-19 pandemic is having major direct and indirect negative impacts on health services overall, including national TB programs and TB services. This adds further to longstanding challenges for tackling MDR-TB such as cost, rollout of diagnostics and drugs, and implementation of latest WHO guidelines for MDR-TB. In light of COVID-19 disruption of TB services, it is anticipated the numbers of MDR-TB cases will rise in 2021 and 2022 and will affect treatment outcomes further. Investing more in development of new TB drugs and shorter MDR-TB treatment regimens is required in anticipation of emerging drug resistance to new TB drug regimens. There is an urgent need for protecting current investments in TB services, sustaining gains being made in TB control and accelerating roll out of TB diagnostic and treatment services.

Towards the Probabilistic Analysis of Small Bowel Capsule Endoscopy Features to Predict Severity of Duodenal Histology in Patients with Villous Atrophy.

Small bowel capsule endoscopy (SBCE) can be complementary to histological assessment of celiac disease (CD) and serology negative villous atrophy (SNVA). Determining the severity of disease on SBCE using statistical machine learning methods can be useful in the follow up of patients. SBCE can play an additional role in differentiating between CD and SNVA. De-identified SBCEs of patients with CD and SNVA were included. Probabilistic analysis of features on SBCE were used to predict severity of duodenal histology and to distinguish between CD and SNVA. Patients with higher Marsh scores were more likely to have a positive SBCE and a continuous distribution of macroscopic features of disease than those with lower Marsh scores. The same pattern was also true for patients with CD when compared to patients with SNVA. The validation accuracy when predicting the severity of Marsh scores and when distinguishing between CD and SNVA was 69.1% in both cases. When the proportions of each SBCE class group within the dataset were included in the classification model, to distinguish between the two pathologies, the validation accuracy increased to 75.3%. The findings of this work suggest that by using features of CD and SNVA on SBCE, predictions can be made of the type of pathology and the severity of disease.

Primary bilateral uveal melanoma: a population-based study and systematic review.

IMPORTANCE: Primary bilateral uveal melanoma (UM) is a rare and incompletely described entity. It is not known how these patients compare to those with unilateral UM. BACKGROUND: We sought to comprehensively characterize and compare patients with primary bilateral and unilateral UM. DESIGN: Retrospective, population-based and systematic review. PARTICIPANTS: Patients with bilateral (n = 52) and unilateral UM (n = 8915). METHODS: We analysed cases of primary bilateral UM from three data sources: (i) the University Hospitals Cleveland Medical Center pathology database from 1996 to 2016 (n = 1); (ii) the Surveillance, Epidemiology and End-Results (SEER)-18 database from 1973 to 2013 (n = 5) and (iii) a systematic review of the English language literature (n = 46). Cases of unilateral UM were obtained from the SEER-18 database from 1973 to 2013 for comparison (n = 8915). MAIN OUTCOME MEASURES: Demographics, clinicopathological characteristics, treatments and survival. RESULTS: There were no differences in sex, race, mean age at diagnosis, site of uveal involvement, metastases at diagnosis, or treatment among patients with bilateral as compared to unilateral UM. Additionally, there were no clinicopathological differences between the two UMs in each patient with bilateral disease. Overall survival did not differ between unilateral and bilateral UM patients, or between bilateral UM patients who presented with, or subsequently developed, bilateral disease. CONCLUSIONS AND RELEVANCE: Bilateral and unilateral UM patients share similar demographics, clinicopathological characteristics, treatments and prognoses. Moreover, the development of bilateral disease does not portend a poorer prognosis and patients should be treated similarly to those with unilateral disease.

A cross-sectional study of preoperative medication adherence and early postoperative recovery.

STUDY OBJECTIVE: To quantify the impact of preoperative medication adherence on recovery length of stays and complication rates. DESIGN: Cross-sectional analytical study. SETTING: Postanesthetic care unit (PACU) of a single-center tertiary hospital. PATIENTS: Surgical patients admitted for surgery at our institution over a 4-month period. INTERVENTION: A data collection tool was used to collect demographic data, length of stay in recovery, prespecified conditions likely to impact on PACU recovery (chronic pain, insulin-dependent diabetes, epilepsy, hypertension, on a methadone program, and Parkinson disease), medication compliance, and complications in PACU. MEASUREMENTS: Differences among categorical variables were assessed for significance using the χ2 test; continuous parametric data were compared using a time to survival analysis via Kaplan-Meier estimates and Cox proportional hazard regressions to account for possible confounders. MAIN RESULTS: Preoperative medication compliance for the prespecified conditions was 65.1%. Patients with a preoperative condition spent more time in the PACU compared to patients without a preoperative condition. Time in PACU was not significantly longer for patients who took their medications compared to those who failed to take their medications. Patients with multiple prespecified conditions were more likely to incur a postoperative complication compared to patients without a prespecified condition. Patients with preoperative hypertension and insulin-dependent diabetes incurred higher complication rates in PACU for medication nonadherence compared to medication adherence. CONCLUSION: This study taken together with accruing evidence suggests that preoperative medication omission remains an ongoing issue that can influence complication rates in the PACU. Patients with preoperative conditions stay longer in PACU, and medication omission was associated with higher rates of certain postoperative complications in PACU. This identifies patients likely to require more interventions and greater recovery resources. Further research into the impact of medication omission on recovery parameters after discharge from the PACU is warranted.