Summary
This retrospective, observational study evaluated patterns of inpatient versus outpatient tumour lysis syndrome (TLS) monitoring during venetoclax ramp‐up in 170 patients with chronic ...lymphocytic leukaemia. The primary outcome was clinical/biochemical TLS. Two clinical and four biochemical TLS occurred (4.1%). Five of the six events occurred in high‐risk patients, four occurred at 20 mg dose and three at the 6‐h time‐point. Inpatient versus outpatient TLS rates within the high‐risk subgroup were 15% and 8%. Risk category was the only predictor of TLS events in multivariate analysis. Outpatient escalation did not associate with clinically meaningful TLS events, suggesting outpatient escalation has manageable associated TLS risks, including in high‐risk cohorts. These observations require confirmation in larger studies.
This study proposes that the term ‘spiritual abuse’ is helpful for an understanding of systemic mistreatment experienced by six former-nuns who belonged to the community ‘Servants of God’s Plan’ ...(Siervas del Plan de Dios, or SPD) in Peru, Chile, Colombia and Ecuador. None of the nuns reported sexual abuse, so the focus in this chapter is on spiritual abuse not sexual abuse. However, when sexual abuse takes place within a religious institution, it is very common for spiritual abuse to be an enabling factor. A better understanding of spiritual abuse can therefore contribute to a better church response to sexual abuse.
Background Prognostic uncertainty is one barrier to engaging in goals-of-care discussions in chronic kidney disease (CKD). The surprise question (“Would you be surprised if this patient died in the ...next 12 months?”) is a tool to assist in prognostication. However, it has not been studied in non−dialysis-dependent CKD and its reliability is unknown. Study Design Observational study. Setting & Participants 388 patients at least 60 years of age with non−dialysis-dependent CKD stages 4 to 5 who were seen at an outpatient nephrology clinic. Predictor Trinary (ie, Yes, Neutral, or No) and binary (Yes or No) surprise question response. Outcomes Mortality, test-retest reliability, and blinded inter-rater reliability. Measurements Baseline comorbid conditions, Charlson Comorbidity Index, cause of CKD, and baseline laboratory values (ie, serum creatinine/estimated glomerular filtration rate, serum albumin, and hemoglobin). Results Median patient age was 71 years with median follow-up of 1.4 years, during which time 52 (13%) patients died. Using the trinary surprise question, providers responded Yes, Neutral, and No for 202 (52%), 80 (21%), and 106 (27%) patients, respectively. About 5%, 15%, and 27% of Yes, Neutral, and No patients died, respectively ( P < 0.001). Trinary surprise question inter-rater reliability was 0.58 (95% CI, 0.42-0.72), and test-retest reliability was 0.63 (95% CI, 0.54–0.72). The trinary surprise question No response had sensitivity and specificity of 55% and 76%, respectively (95% CIs, 38%-71% and 71%-80%, respectively). The binary surprise question had sensitivity of 66% (95% CI, 49%-80%; P = 0.3 vs trinary), but lower specificity of 68% (95% CI, 63%-73%; P = 0.02 vs trinary). Limitations Single center, small number of deaths. Conclusions The surprise question associates with mortality in CKD stages 4 to 5 and demonstrates moderate to good reliability. Future studies should examine how best to deploy the surprise question to facilitate advance care planning in advanced non−dialysis-dependent CKD.
Postural tachycardia syndrome (POTS) is associated with exercise intolerance, hypovolemia, and cardiac atrophy, which may contribute to reduced stroke volume and compensatory exaggerated heart rate ...(HR) increases. Acute volume loading with intravenous (iv) saline reduces HR and improves orthostatic tolerance and symptoms in POTS, but its effect on exercise capacity is unknown. In this study, we determined the effect of iv saline infusion on peak exercise capacity (VO2peak) in POTS. Nineteen patients with POTS participated in a sequential study. VO2peak was measured on two separate study days, following administration of placebo or 1 liter of i.v. saline (NaCl 0.9%). Patients exercised on a semirecumbent bicycle with resistance increased by 25 W every 2 min until maximal effort was achieved. Patients exhibited blood volume deficits (-13.4 ± 1.4% ideal volume), consistent with mild to moderate hypovolemia. At baseline, saline significantly increased stroke volume (saline 80 ± 8 ml vs. placebo 64 ± 4 ml; P = 0.010), increased cardiac output (saline 6.9 ± 0.5 liter/min vs. placebo 5.7 ± 0.2 liter/min; P = 0.021), and reduced systemic vascular resistance (saline 992.6 ± 70.0 dyn-s/cm(5) vs. placebo 1,184.0 ± 50.8 dyn-s/cm(5); P = 0.011), with no effect on HR or blood pressure. During exercise, saline did not produce differences in VO2peak (saline 26.3 ± 1.2 mg·kg(-1)·min(-1) vs. placebo 27.7 ± 1.8 mg·kg(-1)·min(-1); P = 0.615), peak HR saline 174 ± 4 beats per minute (bpm) vs. placebo 175 ± 3 bpm; P = 0.672 or other cardiovascular parameters. These findings suggest that acute volume loading with saline does not improve VO2peak or cardiovascular responses to exercise in POTS, despite improvements in resting hemodynamic function.
Obesity is an important risk factor for the development of insulin resistance. Initial compensatory mechanisms include an increase in insulin levels, which are thought to induce sympathetic ...activation in an attempt to restore energy balance. We have previously shown, however, that sympathetic activity has no beneficial effect on resting energy expenditure in obesity. On the contrary, we hypothesize that sympathetic activation contributes to insulin resistance. To test this hypothesis, we determined insulin sensitivity using a standard hyperinsulinemic euglycemic clamp protocol in obese subjects randomly assigned in a crossover design 1 month apart to receive saline (intact day) or trimetaphan (4 mg/min IV, autonomic blocked day). Whole-body glucose uptake (MBW in mg/kg per minute) was used as index of maximal muscle glucose use. During autonomic blockade, we clamped blood pressure with a concomitant titrated intravenous infusion of the nitric oxide synthase inhibitor N-monomethyl-L-arginine. Of the 21 obese subjects (43±2 years; 35±2 kg/m body mass index) studied, 14 were insulin resistant; they were more obese, had higher plasma glucose and insulin, and had higher muscle sympathetic nerve activity (23.3±1.5 versus 17.2±2.1 burst/min; P=0.03) when compared with insulin-sensitive subjects. Glucose use improved during autonomic blockade in insulin-resistant subjects (MBW 3.8±0.3 blocked versus 3.1±0.3 mg/kg per minute intact; P=0.025), with no effect in the insulin-sensitive group. These findings support the concept that sympathetic activation contributes to insulin resistance in obesity and may result in a feedback loop whereby the compensatory increase in insulin levels contributes to greater sympathetic activation.
Resumen Este estudio propone que el término “abuso espiritual” es útil para comprender el maltrato sistémico experimentado por seis ex religiosas que pertenecieron a la comunidad “Siervas del Plan de ...Dios” (SPD) de Perú, Chile, Colombia y Ecuador. Hay relativamente pocos textos sobre el tema, lo que es particularmente significativo ya que el abuso de religiosas ha recibido atención mundial en los últimos años. El artículo pretende identificar mejor las áreas que las comunidades religiosas necesitarían abordar para trabajar esta problemática de manera positiva e informada.
Impaired nitric oxide (NO) vasodilation (endothelial dysfunction) is associated with obesity and thought to be a factor in the development of hypertension. We previously found that NO synthesis ...inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade, suggesting that impaired NO vasodilation is secondary to sympathetic activation. We tested this hypothesis by determining the effect of autonomic blockade (trimethaphan 4 mg/min IV) on NO-mediated vasodilation (increase in forearm blood flow to intrabrachial acetylcholine) compared with endothelial-independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30<body mass index<40 kg/m(2)). Acetylcholine and sodium nitroprusside were given at equipotent doses (10, 30, and 50 μg/min and 1, 2, and 3 μg/min, respectively) to 14 obese subjects (49±3.6 years, 34±1 kg/m(2), 165/94±7/6 mm Hg), on separate occasions 1 month apart, randomly assigned. Autonomic blockade increased basal forearm blood flow (from 3.9±0.7 to 5.2±1.2 mL/100 mL per minute, P=0.078). As expected, NO-mediated vasodilation was blunted on the intact day compared with NO-independent vasodilation; forearm blood flow increased from 3.6±0.6 to 10.1±1.1 with the highest dose of nitroprusside, but only from 3.7±0.4 to 7.2±0.8 mL/100 mL per minute with the highest dose of acetylcholine, P<0.05. In contrast, forearm blood flow responses to acetylcholine were restored by autonomic blockade and were no longer different to nitroprusside (from 6.2±1.1 to 11.4±1.6 mL/100 mL per minute and from 5.2±0.9 to 12.5±0.9, respectively, P=0.58). Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity-associated hypertension and provides further rationale to explore it as a therapeutic target.
According to the World Health Organization, approximately 15% of the global population is affected by mental health or substance use disorders. These conditions contribute significantly to the global ...disease burden, which has worsened because of the direct and indirect effects of COVID-19. In Mexico, a quarter of the population between the ages of 18 and 65 years who reside in urban areas present a mental health condition. The presence of a mental or substance abuse disorder is behind a significant percentage of suicidal behaviors in Mexico, where only 1 in 5 of those who have these disorders receive any treatment.
This study aims to develop, deploy, and evaluate a computational platform to support the early detection and intervention of mental and substance use disorders in secondary and high schools as well as primary care units. The platform also aims to facilitate monitoring, treatment, and epidemiological surveillance ultimately helping specialized health units at the secondary level of care.
The development and evaluation of the proposed computational platform will run during 3 stages. In stage 1, the identification of the functional and user requirements and the implementation of the modules to support the screening, follow-up, treatment, and epidemiological surveillance will be performed. In stage 2, the initial deployment of the screening module will be carried out in a set of secondary and high schools, as well as the deployment of the modules to support the follow-up, treatment, and epidemiological surveillance processes in primary and secondary care health units. In parallel, during stage 2, patient applications to support early interventions and continuous monitoring will also be developed. Finally, during stage 3, the deployment of the complete platform will be performed jointly with a quantitative and qualitative evaluation.
The screening process has started, and 6 schools have been currently enrolled. As of February 2023, a total of 1501 students have undergone screening, and the referral of those students presenting a risk in mental health or substance use to primary care units has also started. The development, deployment, and evaluation of all the modules of the proposed platform are expected to be completed by late 2024.
The expected results of this study are to impact a better integration between the different levels of health care, from early detection to follow-up and epidemiological surveillance of mental and substance use disorders contributing to reducing the gap in the attention to these problems in the community.
DERR1-10.2196/44607.
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