Determinants of non-adherence to anti-TB treatment in high income, low TB incidence settings: a scoping review.

BACKGROUND: Improving adherence to anti-TB treatment is a public health priority in high-income, low incidence (HILI) regions. We conducted a scoping review to identify reported determinants of non-adherence in HILI settings.METHODS: Key terms related to TB, treatment and adherence were used to search MEDLINE, EMBASE, Web of Science, PsycINFO and CINAHL in June 2019. Quantitative studies examining determinants (demographic, clinical, health systems or psychosocial) of non-adherence to anti-TB treatment in HILI settings were included.RESULTS: From 10,801 results, we identified 24 relevant studies from 10 countries. Definitions and methods of assessing adherence were highly variable, as were documented levels of non-adherence (0.9-89%). Demographic factors were assessed in all studies and clinical factors were frequently assessed (23/24). Determinants commonly associated with non-adherence were homelessness, incarceration, and alcohol or drug misuse. Health system (8/24) and psychosocial factors (6/24) were less commonly evaluated.CONCLUSION: Our review identified some key factors associated with non-adherence to anti-TB treatment in HILI settings. Modifiable determinants such as psychosocial factors are under-evidenced and should be further explored, as these may be better targeted by adherence support. There is an urgent need to standardise definitions and measurement of adherence to more accurately identify the strongest determinants.

Coping with COVID-19: ventilator splitting with differential driving pressures using standard hospital equipment.

The global COVID-19 pandemic has led to a worldwide shortage of ventilators. This shortage has initiated discussions on how to support multiple patients with a single ventilator (ventilator splitting). Ventilator splitting is incompletely tested, experimental and the effects have not been fully characterised. This study investigated the effect of ventilator splitting on system variables (inspiratory pressure, flow and volume) and the possibility of different ventilation targets for each limb using only standard hospital equipment. Experiments were conducted on two test lungs with different compliances (0.02 l.cmH2 O-1 and 0.04 l.cmH2 O-1 ). The ventilator was used in both pressure and volume control modes and was set to ventilate the low compliance lungs at end-tidal volumes of 500 ± 20 ml. A flow restrictor apparatus consisting of a Hoffman clamp and tracheal tube was connected in series to the inspiratory limb of the high compliance test lungs and the resistance modified to achieve end-tidal volumes of 500 ± 20 ml. The restriction apparatus successfully modified the inspiratory pressure, minute ventilation and volume delivered to the high compliance test lungs in both pressure control (27.3-17.8 cmH2 O, 15.2-8.0 l.min-1 and 980-499 ml, respectively) and volume control (21.0-16.7 cmH2 O, 10.7-7.9 l.min-1 and 659-498 ml, respectively) ventilation modes. Ventilator splitting is not condoned by the authors. However, these experiments demonstrate the capacity to simultaneously ventilate two test lungs of different compliances, and using only standard hospital equipment, modify the delivered pressure, flow and volume in each test lung.

The role of neuronal GABA(A) receptor subunit mutations in idiopathic generalized epilepsies.

Rare GABA(A) receptor gamma2 and alpha1 subunit mutations of pathogenic effect have been described segregating in families with "monogenic" epilepsies. We now report globally on the genetic variation contained within all 16 neuronal GABA(A) receptor subunit genes from the one patient cohort. The cohort consists of GEFS(+), FS, and IGE subgroups as either sporadic cases or index cases from small families, with one index case from one large IGE family. The rarity of mutations and coding variation in general across all of the subunits suggests a low tolerance for mutations affecting GABA mediated neuronal inhibition. Characterization of the broader channelopathy load associated with susceptibility to these common epilepsies mostly with complex genetics will need to be expanded beyond the family of GABA(A) receptor subunits to all families of neuronal ion channels and their interacting molecules by systematic mutation detection associated with functional investigation of their naturally occurring genetic variations.

Calcified plaque is common in the carotid and femoral arteries of dialysis patients without clinical vascular disease.

BACKGROUND: Cardiac and vascular mortality are common in end-stage renal disease (ERSD) and are often attributed to accelerated atherosclerosis. SUBJECTS AND METHODS: We studied 24 non-diabetic ESRD patients without cardiac or vascular disease (M = 12, F = 12) and 24 age-, sex- and race-matched healthy controls. All underwent B-mode ultrasound for carotid and femoral intima media thickness (IMT) and plaque (% stenosis) together with blood pressure (BP), and echocardiograms to determine left ventricular mass. RESULTS: Both BP and mean IMT were similar in patients and controls. However, discrete plaque was present in 71% (17/24) of patients compared with 21% (5/24) of controls (P = 0.001), and % stenosis was greater in patients (carotid 12.2 +/- 11% vs 2.3 +/- 5.9%, P < 0.0004; femoral 16.4 +/- 19.1% vs 3.1 +/- 6.4%, P < 0.003). Plaque was soft/atheromatous in 3 of the 5 controls, but not in any of the 17 patients (P = 0.007), all of whom had calcified lesions. BP and cholesterol were not correlated with IMT or plaque in patients, but in control subjects carotid IMT was correlated with systolic BP (r = 0.66, P < 0.0005) and diastolic BP (r = 0.45, P < 0.03). In patients, the only independent variables related to vascular morphology were serum albumin which was inversely related to IMT (P < 0.03) and to plaque (carotid P < 0.05, femoral P < 0.02) and age, which was related to femoral plaque only (P < 0.04). Left ventricular end-diastolic internal dimension, not LVMI, correlated positively with carotid IMT (P < 0.04). CONCLUSION: Our results show that calcified plaque is common in ESRD patients and hypoalbuminaemia may be an associated factor.

Women, resources, and dispersal in nineteenth-century Sweden.

In a recent study, female dispersal in nineteenth-century Sweden has been found to correlate negatively with access to resources: women with limited access to local resources tended to migrate more frequently. In this paper I review the literature to explore whether this observed correlation was derived from a relationship in which a woman's limited access to resources worsened her position in the marriage market and led to migration, as a strategy to improve resources and this position. Many studies within a variety of disciplines indicate that a woman's propensity to disperse from her parish of birth variedinversely with her propensity to inherit resources. My review of the literature suggests that the less likely a woman was to inherit resources, the lower her probability of marriage, the later her expected age at marriage, and the earlier she left home, presumably to improve her resource base for marriage.