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Recent evidence suggests Trendelenburg positioning can produce a significant rise in intra-ocular pressure. Peri-operative vision loss in patients undergoing laparoscopic colorectal surgery has been reported with the rise in intra-ocular pressure suggested as a possible factor. Acetazolamide decreases intra-ocular pressure by reducing the formation of aqueous humour, so we aimed to investigate if it could attenuate the intra-ocular pressure rise that can occur in the Trendelenburg position. Nine healthy volunteers were recruited and randomly assigned to a double-blind crossover comparison of placebo or acetazolamide with a minimal 4 days' washout period before the second study day. One and a half hours after taking the medication, volunteers lay head-down at 17° for 4 h. Intraocular pressure measurements were repeated in both eyes every 30 min over a 4-h period. There were two males and seven female volunteers, with a mean (SD) age of 54.3 (18.5) years. The mean (SD) increase in intra-ocular pressure following 4 h in the Trendelenburg position was 3.17 (4.63) mmHg after the placebo, and 0.02 (4.01) mmHg (p = 0.02) after acetazolamide. We have shown than acetazolamide can attenuate the rise that occurs in intra-ocular pressure when in the Trendelenburg position. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidence suggests that covalent modifications to the genomic platform in the brain, that is DNA and its surrounding histones, provide a stable potentially lifelong mechanism for remembrance. Consequently, the making and unmaking of memories is accessible through pharmacological manipulations of these modifications. This has implications for psychotherapy and long-term rehabilitation of CNS disorders. We hypothesize that by enhancing learning through pharmacologically manipulating ‘epigenetic’ parameters, the effects of psychotherapies and rehabilitation can be enhanced. [Copyright &y& Elsevier]

The Revised National Tuberculosis Control Programme (RNTCP), which incorporated the WHO DOTS strategy was introduced in India in the mid-1990s. An operational research project was conducted between 1996 and 1998 to assess the needs and perspectives of patients and providers in two chest clinics in Delhi, Moti Nagar and Nehru Nagar, during the introduction of the new strategy. This paper reports on the findings of the project, concentrating on information collected from 40 in-depth interviews with patient defaulters and from non-participant observations in clinics and directly observed treatment centres. In Moti Nagar chest clinic, 117 of 1786 (6.5%) patients and 195 of 1890 (10%) patients in Nehru Nagar left care before their treatment was complete. It was argued that the reasons for default stem from a poor correlation between patient and programme needs and priorities, and from particular characteristics of the disease and its treatment. Patient needs that were not met by the health system included convenient clinic timings, arrangements for the provision for treatment in the event of a family emergency and provision for complicated cases like alcoholics. The problems facing the provider were poor interpersonal communication with the health staff, lack of attention and support at the clinic, difficulty for patients to re-enter the system if they missed treatment and, in certain areas, long distances to the clinic. Problems related to diseases were inability of the staff to deal with drug side-effects, and patients' conception of equating well-being with cure. Simple, practical measures could improve the provision of tuberculosis (TB) treatment: more flexible hours, allowances for poor patients to reach the clinics and training health care staff for respectful communication and monitoring drug side-effects. The findings indicate a need to rethink the label of 'defaulter' often given to the patients. The important areas for future operational research is also highlighted. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of good quality evidence regarding the best therapeutic option for acute control of blood pressure during acute hypertensive emergency of pregnancy.Objective: We sought to compare the efficacy of intravenously administered hydralazine and oral nifedipine for acute blood pressure control in acute hypertensive emergency of pregnancy.Study Design: In this double-blind, randomized, controlled trial, pregnant women (≥24 weeks period of gestation) with sustained increase in systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥110 mm Hg were randomized to receive intravenous hydralazine injection in doses of 5, 10, 10, and 10 mg and a placebo tablet or oral nifedipine (10 mg tablet up to 4 doses) and intravenous saline injection every 20 minutes until the target blood pressure of 150 mm Hg systolic and ≤100 mm Hg diastolic was achieved. Crossover treatment was administered if the initial treatment failed. The primary outcome of the study was time necessary to achieve target blood pressure. The secondary outcomes were the number of dosages required, adverse maternal and neonatal effects, and perinatal outcome.Results: From December 2014 through September 2015, we enrolled 60 patients. The median time to achieve target blood pressure was 40 minutes in both groups (intravenous hydralazine and oral nifedipine) (interquartile interval 5 and 40 minutes, respectively, P = .809). The median dose requirement in both groups was 2 (intravenous hydralazine and oral nifedipine) (interquartile range 1 and 2 doses, respectively, P = .625). Intravenous hydralazine was associated with statistically significantly higher occurrence of vomiting (9/30 vs 2/30, respectively, P = .042). No serious adverse maternal or perinatal side effects were witnessed in either group.Conclusion: Both intravenous hydralazine and oral nifedipine are equally effective in lowering of blood pressure in acute hypertensive emergency of pregnancy. [ABSTRACT FROM AUTHOR]

Study Objective: Copperhead snake (Agkistrodon contortrix) envenomation causes limb injury resulting in pain and disability. It is not known whether antivenom administration improves limb function. We determine whether administration of antivenom improves recovery from limb injury in patients envenomated by copperhead snakes.Methods: From August 2013 through November 2015, we performed a multicenter, randomized, double-blind, placebo-controlled, clinical trial to evaluate the effect of ovine Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) antivenom therapy on recovery of limb function in patients with copperhead snake envenomation at 14 days postenvenomation. The study setting was 18 emergency departments in regions of the United States where copperhead snakes are endemic. Consecutive patients aged 12 years or older with mild- to moderate-severity envenomation received either FabAV or placebo. The primary outcome was limb function 14 days after envenomation, measured by the Patient-Specific Functional Scale. Additional outcomes included the Patient-Specific Functional Scale at other points; the Disorders of the Arm, Shoulder, and Hand, Lower Extremity Functional Scale, and Patient's Global Impression of Change instruments; grip strength; walking speed; quality of life (Patient-Reported Outcomes Measurement Information System Physical Fucntion-10); pain; and analgesic use.Results: Seventy-four patients received study drug (45 FabAV, 29 placebo). Mean age was 43 years (range 12 to 86 years). Fifty-three percent were men, 62% had lower extremity envenomation, and 88% had mild initial severity. The primary outcome, the least square mean Patient-Specific Functional Scale score at 14 days postenvenomation, was 8.6 for FabAV-treated subjects and 7.4 for placebo recipients (difference 1.2; 95% confidence interval 0.1 to 2.3; P=.04). Additional outcome assessments generally favored FabAV. More FabAV-treated subjects experienced treatment-emergent adverse events (56% versus 28%), but few were serious (1 in each group).Conclusion: Treatment with FabAV reduces limb disability measured by the Patient-Specific Functional Scale 14 days after copperhead envenomation. [ABSTRACT FROM AUTHOR]

Background: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe.Methods: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons.Results: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group.Conclusions: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.). [ABSTRACT FROM AUTHOR]