Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

Laboratory comparison of stool processing methods for Xpert® Ultra.

TB disease diagnosis in children is difficult due to non-specific symptoms, paucibacillary disease and the need for invasive procedures to obtain diagnostic specimens. In many settings, these specimens are simply not collected and therefore stool, easily obtained, has emerged as a promising specimen for the diagnosis of child TB. In this study, stool from a healthy adult was spiked with known concentrations of bacille Calmette-Guérin vaccine and tested using the Xpert® Ultra assay to determine the relative detection and error rate associated with four different published stool processing methods.

Le diagnostic de TB maladie chez l'enfant est difficile en raison de la non spécificité de symptômes, de son caractère paucibacillaire et du besoin de procédures invasives pour obtenir des échantillons diagnostiques. Dans de nombreux contextes, ces échantillons ne sont tout simplement pas recueillis ; c'est pourquoi les selles, faciles à obtenir, sont apparus comme un échantillon prometteur pour le diagnostic de la TB de l'enfant. Dans cette étude, des selles d'un adulte en bonne santé ont été enrichies avec des concentrations connues de vaccin Bacille Calmette-Guérin et testés avec le test Xpert Ultra pour déterminer les taux relatifs de détection et d'erreur associés à quatre différentes méthodes publiées de traitement des selles.

Bedaquiline and delamanid result in low rates of unfavourable outcomes among TB patients in Eswatini.

SETTING: Since 2015, Eswatini has been scaling up bedaquiline (BDQ) and delamanid (DLM) based drug-resistant TB treatment regimens under programmatic conditions.OBJECTIVE: Identification of factors associated with treatment outcomes in patients receiving BDQ and/or DLM either as a new treatment initiation or drug substitution.DESIGN: This is a retrospective cohort study of patients receiving BDQ and/or DLM in Eswatini between March 2015 and October 2018. We describe factors associated with unfavourable treatment outcomes (death, lost to follow-up, treatment failure and amplification of resistance) and culture conversion using multivariable flexible parametric survival and competing-risks regression analyses.RESULTS: Of 352 patients receiving BDQ and/or DLM, 7.8% and 21.2% had an unfavourable treatment outcome at 6 and 24 months, respectively. Predictors were age ≥ 60 years (adjusted hazard ratio aHR 4.49, 95%CI 1.61-12.57) vs. age 20-39 years, and a treatment regimen combining both drugs (aHR 4.49, 95%CI 1.61-12.57) vs. BDQ only. The probability of culture conversion was increased for two health facilities and patients with a poly resistance profile (adjusted sub-hazard ratio 2.01, 95%CI 1.13-3.59) vs. multidrug resistance.CONCLUSION: Single use of BDQ or DLM was associated with low rates of unfavourable outcomes, suggesting that these medications may be effectively adopted at scale under routine programmatic conditions. Combined use of BDQ and DLM was a risk factor for unfavourable outcomes and should prompt for collection of more data on the combined use of these medications.

Management of patients with multidrug-resistant tuberculosis.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

Time of onset of carcinoma of the stomach following surgical treatment of duodenal ulcer.

In a review of 1,092 patients with histologically proved carcinoma of the stomach, it was found that 40 patients (3.8 per cent) had previously undergone surgical treatment of a duodenal ulcer. In 13 patients, truncal vagotomy had been carried out, while 27 patients had a partial gastrectomy. Patients having truncal vagotomy and who subsequently had carcinoma of the stomach develop did so at a significantly earlier age than those having partial gastrectomy (55 years compared with 64 years). Carcinoma of the stomach was diagnosed after an average interval of 8.5 years in the vagotomy group compared with 24.0 years in the nonvagotomy group. Possible explanations for this observation are considered. Patients in the vagotomy group were less likely to have a resectable tumor.

Response to insulin of the intact stomach in patients with duodenal ulcer.

Insulin tests were performed on 47 duodenal ulcer patients with intact stomachs. Only 20 had a positive response to the test judged positive by the criteria of Hollander in the first 45 minutes after the insulin. Twenty became positive between 45 and 60 minutes, and in five the response was not noted until the second hour. Surprisingly, two patients had apparently negative responses to the insulin. While caution is necessary in comparing responses of the intact stomach to those after vagotomy operations, the occurrence of the ;late positive' and negative patterns of response to insulin in the intact stomach may give rise to reservations about the interpretation of these types of response after vagotomy.

Exocrine secretory responses of the pancreas to insulin and to a meat meal in dogs.

Studies in five dogs with chronic pancreatic and gastric fistulae have shown that insulin-induced vagal stimulation of the pancreas (gastric fistula open) resulted in protein and bicarbonate outputs very much smaller than those obtained with a 400-g meat meal. However, when the insulin-activated gastric acid secretion was allowed access to the duodenum (gastric fistula closed) peak outputs of both bicarbonate and protein were observed which were closely similar to the response to the meal. These findings suggest that insulin-induced hypoglycaemia results in stimulation of the pancreas within the physiological range when gastric acid is allowed access to the duodenum with consequent release of secretin.

Truncal vagotomy and drainage for chronic duodenal ulcer disease: a controlled trial.

The results of elective truncal vagotomy and drainage in 547 duodenal ulcer patients are reported. Altogether, 204 patients were randomly allocated to pyloroplasty and 200 to gastrojejunostomy. In 101 patients gastrojejunostomy was electively chosen and in 42 patients the duodenum was opened to confirm the diagnosis. Operative mortality was 0.5%, the incidence of proved recurrent ulceration 3.3%, severe dumping 2%, and severe diarrhoea 1.1%. There were no significant differences between the groups, with the exception of bilious vomiting which occurred more often in patients with gastrojejunostomy.

Results of adrenal surgery in patients with hypertension, aldosterone excess, and low plasma renin concentration.

Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery. There was a highly significant fall in mean systolic and diastolic pressures after the operation. The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients. There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.