Exercise in Futility or do CART or MEWS Prevent Errors?

How to cite this article: Rao RMG. Exercise in Futility or do CART or MEWS Prevent Errors? Indian J Crit Care Med 2022;26(7):765-766.

ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice.

BACKGROUND: Acetaldehyde, the toxic ethanol (EtOH) metabolite, disrupts intestinal epithelial barrier function. Aldehyde dehydrogenase (ALDH) detoxifies acetaldehyde into acetate. Subpopulations of Asians and Native Americans show polymorphism with loss-of-function mutations in ALDH2. We evaluated the effect of ALDH2 deficiency on EtOH-induced disruption of intestinal epithelial tight junctions and adherens junctions, gut barrier dysfunction, and liver injury. METHODS: Wild-type and ALDH2-deficient mice were fed EtOH (1 to 6%) in Lieber-DeCarli diet for 4 weeks. Gut permeability in vivo was measured by plasma-to-luminal flux of FITC-inulin, tight junction and adherens junction integrity was analyzed by confocal microscopy, and liver injury was assessed by the analysis of plasma transaminase activity, histopathology, and liver triglyceride. RESULTS: EtOH feeding elevated colonic mucosal acetaldehyde, which was significantly greater in ALDH2-deficient mice. ALDH2(-/-) mice showed a drastic reduction in the EtOH diet intake. Therefore, this study was continued only in wild-type and ALDH2(+/-) mice. EtOH feeding elevated mucosal inulin permeability in distal colon, but not in proximal colon, ileum, or jejunum of wild-type mice. In ALDH2(+/-) mice, EtOH-induced inulin permeability in distal colon was not only higher than that in wild-type mice, but inulin permeability was also elevated in the proximal colon, ileum, and jejunum. Greater inulin permeability in distal colon of ALDH2(+/-) mice was associated with a more severe redistribution of tight junction and adherens junction proteins from the intercellular junctions. In ALDH2(+/-) mice, but not in wild-type mice, EtOH feeding caused a loss of junctional distribution of tight junction and adherens junction proteins in the ileum. Histopathology, plasma transaminases, and liver triglyceride analyses showed that EtOH-induced liver damage was significantly greater in ALDH2(+/-) mice compared to wild-type mice. CONCLUSIONS: These data demonstrate that ALDH2 deficiency enhances EtOH-induced disruption of intestinal epithelial tight junctions, barrier dysfunction, and liver damage.

Building a primary care/research partnership: lessons learned from a telehealth intervention for diabetes and depression.

INTRODUCTION: Evidence-based interventions are often poorly translated into primary care settings due to inadequate integration into organizational cultures and clinical workflows. Study designs that blend evaluation of effectiveness and implementation may enhance uptake of interventions into primary care settings. Community-Based Participatory Research (CBPR) models are useful for developing partnerships between research teams and primary care clinical partners to test blended study designs. METHODS: We conducted a formative evaluation of partnership building between a health services research team and a primary care community in US Veterans Affairs Health System to conduct a randomized effectiveness trial of an intervention embedded in routine primary care. The formative evaluation used qualitative data drawn from research/clinical partnership meetings. Data were coded and analysed using qualitative framework analysis. RESULTS: The CBPR model guided development of a research/clinical partnership based on a facilitation team consisting of 'external facilitators' (research team), 'internal facilitators' (primary care leadership) and a 'clinical advisory committee' drawn from the primary care community. Qualitative themes focused on: how the intervention components ('evidence') aligned with local clinical cultures, barriers and facilitators to acceptance and adoption of the intervention processes within the context of clinical workflows and identified 'facilitators' of intervention uptake and sustainability. CONCLUSION: A CBPR model can guide the development of research/clinical partnerships. Partnerships can identify barriers and craft modifications to intervention procedures that promote integration and into primary care workflows. Formative research/clinical partnerships are critical for designing and testing interventions focused on implementation and sustainability of new evidence within routine primary care.

Proactive outreach for smokers using VHA mental health clinics: protocol for a patient-randomized clinical trial.

BACKGROUND: Persons with a mental health diagnosis have high rates of tobacco use and face numerous barriers to cessation including high levels of nicotine dependence, low rates of tobacco treatment referrals from mental health providers, and limited availability of tobacco treatment targeted to their needs. This manuscript describes the rationale and methods of a clinical trial with the following aims: 1) Compare the reach and efficacy of a proactive telephone-based tobacco cessation program for Veterans Health Administration (VHA) mental health clinic patients to VHA usual care and 2) Model longitudinal associations between baseline patient characteristics and long-term abstinence. METHODS/DESIGN: We will use the electronic medical record to identify patients across four VHA healthcare facilities who have a clinical reminder code indicating current tobacco use in the past six months and who have had a mental health clinic visit in the past 12 months. We will send each patient an introductory letter and baseline survey. Survey respondents (N = 3840) will be randomized in a 1:1 fashion to intervention or control. Control participants will receive VHA usual care. Intervention participants will receive proactive motivational telephone outreach to offer tobacco treatment. Intervention participants interested in treatment will receive eight weeks of nicotine replacement therapy plus eight sessions of specialized telephone counseling over two months, followed by monthly maintenance counseling for four months. We will conduct telephone surveys with participants at six and 12 months to assess study outcomes. We will collect a mailed saliva sample from patients reporting 7-day abstinence on the telephone surveys. The primary outcome will be cotinine-validated abstinence at 12-month follow-up. DISCUSSION: Mental health patients are a high-risk smoking population with significant barriers to cessation. This study will evaluate the efficacy of a program that proactively reaches out to smokers with a mental health treatment history to engage them into telephone cessation counseling targeted to the needs of mental health patients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01737281 (registered November 5, 2012).

Behavioral health coaching for rural veterans with diabetes and depression: a patient randomized effectiveness implementation trial.

BACKGROUND: Depression and diabetes cause significant burden for patients and the healthcare system and, when co-occurring, result in poorer self-care behaviors and worse glycemic control than for either condition alone. However, the clinical management of these comorbid conditions is complicated by a host of patient, provider, and system-level barriers that are especially problematic for patients in rural locations. Patient-centered medical homes provide an opportunity to integrate mental and physical health care to address the multifaceted needs of complex comorbid conditions. Presently, there is a need to not only develop robust clinical interventions for complex medically ill patients but also to find feasible ways to embed these interventions into the frontlines of existing primary care practices. METHODS/DESIGN: This randomized controlled trial uses a hybrid effectiveness-implementation design to evaluate the Healthy Outcomes through Patient Empowerment (HOPE) intervention, which seeks to simultaneously address diabetes and depression for rural veterans in Southeast Texas. A total of 242 Veterans with uncontrolled diabetes and comorbid symptoms of depression will be recruited and randomized to either the HOPE intervention or to a usual-care arm. Participants will be evaluated on a host of diabetes and depression-related measures at baseline and 6- and 12-month follow-up. The trial has two primary goals: 1) to examine the effectiveness of the intervention on both physical (diabetes) and emotional health (depression) outcomes and 2) to simultaneously pilot test a multifaceted implementation strategy designed to increase fidelity and utilization of the intervention by coaches interfacing within the primary care setting. DISCUSSION: This ongoing blended effectiveness-implementation design holds the potential to advance the science and practice of caring for complex medically ill patients within the constraints of a busy patient-centered medical home. TRIAL REGISTRATION: Behavioral Activation Therapy for Rural Veterans with Diabetes and Depression: NCT01572389.

Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study.

BACKGROUND: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma. METHODS: In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375 mg/m(2) per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967. FINDINGS: 71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively). INTERPRETATION: mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma. FUNDING: National Institutes of Health and the Predolin Foundation.

Novel Quinolone Derivatives: Synthesis and Antioxidant Activity.

Novel quinolone derivatives have been designed and readily synthesized according to a simple protocol including O-alkylation and Claisen rearrangement processes. Structures of the synthesized compounds have been confirmed by IR, 1H and 13C NMR, and mass spectra. The new products have been tested for their antioxidant activity, and two of those demonstrate high antioxidant activity.

A case of herniated gravid uterus through a laparotomy scar.

A 36-year-old manual worker presented in her second pregnancy at 34 weeks of gestation with an unusual bulge of her abdomen. The lower abdominal bulge turned out to be her gravid uterus herniated through an anterior abdominal wall incisional hernia which is a rare but serious obstetric situation with complications such as premature labour, intrauterine growth retardation, strangulation, intrauterine death and rupture of the lower uterine segment been reported. We had a successful outcome by conservative treatment till 38 weeks of gestation followed by an elective lower segment Caesarean section with hernia repair. Incisional hernia is a frequent complication of abdominal wall closure and the management of pregnancy with a large incisional hernia with gravid uterus in its sac is challenging.

Crescentic glomerulonephritis and dense deposit disease in a woman with breast carcinoma on immunosuppressive chemotherapy.

The authors describe an unusual case of acute renal failure in a 50-year-old woman with a history of breast carcinoma. The breast carcinoma was treated with 4 cycles of chemotherapy. After chemotherapy, she felt fatigued and noticed decreased urine output. Her serum creatinine level had risen from 0.8 to 10.1 mg/dL (71 to 893 micromol/L). Renal biopsy was done that showed a severe crescentic glomerulonephritis secondary to dense deposit disease. This case is extremely unusual in that: (1) Dense deposit disease developed in a 50-year-old woman, whereas it is primarily a disease of children and young adults, and (2) the patient was being treated with immunosuppressive chemotherapy for breast carcinoma when dense deposit disease developed, thus posing a therapeutic dilemma.

Physicians' diagnostic accuracy, confidence, and resource requests: a vignette study.

IMPORTANCE: Little is known about the relationship between physicians' diagnostic accuracy and their confidence in that accuracy. OBJECTIVE: To evaluate how physicians' diagnostic calibration, defined as the relationship between diagnostic accuracy and confidence in that accuracy, changes with evolution of the diagnostic process and with increasing diagnostic difficulty of clinical case vignettes. DESIGN, SETTING, AND PARTICIPANTS: We recruited general internists from an online physician community and asked them to diagnose 4 previously validated case vignettes of variable difficulty (2 easier; 2 more difficult). Cases were presented in a web-based format and divided into 4 sequential phases simulating diagnosis evolution: history, physical examination, general diagnostic testing data, and definitive diagnostic testing. After each phase, physicians recorded 1 to 3 differential diagnoses and corresponding judgments of confidence. Before being presented with definitive diagnostic data, physicians were asked to identify additional resources they would require to diagnose each case (ie, additional tests, second opinions, curbside consultations, referrals, and reference materials). MAIN OUTCOMES AND MEASURES: Diagnostic accuracy (scored as 0 or 1), confidence in diagnostic accuracy (on a scale of 0-10), diagnostic calibration, and whether additional resources were requested (no or yes). RESULTS: A total of 118 physicians with broad geographical representation within the United States correctly diagnosed 55.3% of easier and 5.8% of more difficult cases (P < .001). Despite a large difference in diagnostic accuracy between easier and more difficult cases, the difference in confidence was relatively small (7.2 vs 6.4 out of 10, for easier and more difficult cases, respectively) (P < .001) and likely clinically insignificant. Overall, diagnostic calibration was worse for more difficult cases (P < .001) and characterized by overconfidence in accuracy. Higher confidence was related to decreased requests for additional diagnostic tests (P = .01); higher case difficulty was related to more requests for additional reference materials (P = .01). CONCLUSIONS AND RELEVANCE: Our study suggests that physicians' level of confidence may be relatively insensitive to both diagnostic accuracy and case difficulty. This mismatch might prevent physicians from reexamining difficult cases where their diagnosis may be incorrect.

Comparative effectiveness of goal setting in diabetes mellitus group clinics: randomized clinical trial.

BACKGROUND: Diabetes mellitus (DM) group clinics can effectively control hypertension, but data to support glycemic control are equivocal. This study evaluated the comparative effectiveness of 2 DM group clinic interventions on glycosylated hemoglobin (HbA(1c)) levels in primary care. METHODS: Eighty-seven participants were recruited from a DM registry of a single regional Veterans Affairs medical center to participate in an open, randomized comparative effectiveness study. Two primary care-based DM group interventions of 3 months' duration were compared. Empowering Patients in Care (EPIC) was a clinician-led, patient-centered group clinic consisting of 4 sessions on setting self-management action plans (diet, exercise, home monitoring, medications, etc) and communicating about progress with action plans. The comparison intervention consisted of group education sessions with a DM educator and dietician followed by an additional visit with one's primary care provider. Hemoglobin A(1c) levels were compared after intervention and at the 1-year follow-up. RESULTS: Participants in the EPIC intervention had significantly greater improvements in HbA(1c) levels immediately following the active intervention (8.86%-8.04% vs 8.74%-8.70% of total hemoglobin; mean [SD] between-group difference 0.67% [1.3%]; P=.03), and these differences persisted at the 1 year follow-up (0.59% [1.4%], P=.05). A repeated-measures analysis using all study time points found a significant time-by-treatment interaction effect on HbA(1c) levels favoring the EPIC intervention (F(2,85)=3.55; P=.03). The effect of the time-by-treatment interaction seems to be partially mediated by DM self-efficacy (F(1,85)=10.39; P=.002). CONCLUSION: Primary care-based DM group clinics that include structured goal-setting approaches to self-management can significantly improve HbA(1c) levels after intervention and maintain improvements for 1 year. Trial Registration clinicaltrials.gov Identifier: NCT00481286.

Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1.

PURPOSE: Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. METHODS: A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. RESULTS: Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. CONCLUSION: This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.