Abstract

Endovascular coiling (EC) has been identified in systematic reviews and meta-analyses to produce more favourable clinical outcomes in comparison to neurosurgical clipping (NC) when surgically treating a subarachnoid haemorrhage from a ruptured aneurysm. Cost-effectiveness analyses between both interventions have been done, but no cost-utility analysis has yet been published. This systematic review aims to perform an economic analysis of the relative utility outcomes and costs from both treatments in the UK. A cost-utility analysis was performed from the perspective of the National Health Service (NHS), over a 1-year analytic horizon. Outcomes were obtained from the randomised International Subarachnoid Aneurysm Trial (ISAT) and measured in terms of the patient's modified Rankin scale (mRS) grade, a 6-point disability scale that aims to quantify a patient's functional outcome following a stroke. The mRS score was weighted against the Euro-QoL 5-dimension (EQ-5D), with each state assigned a weighted utility value which was then converted into quality-adjusted life years (QALYs). A sensitivity analysis using different utility dimensions was performed to identify any variation in incremental cost-effectiveness ratio (ICER) if different input variables were used. Costs were measured in pounds sterling (£) and discounted by 3.5% to 2020/2021 prices. The cost-utility analysis showed an ICER of - £144,004 incurred for every QALY gained when EC was utilised over NC. At NICE's upper willingness-to-pay (WTP) threshold of £30,000, EC offered a monetary net benefit (MNB) of £7934.63 and health net benefit (HNB) of 0.264 higher than NC. At NICE's lower WTP threshold of £20,000, EC offered an MNB of £7478.63 and HNB of 0.374 higher than NC. EC was found to be more 'cost-effective' than NC, with an ICER in the bottom right quadrant of the cost-effectiveness plane-indicating that it offers greater benefits at lower costs. This is supported by the ICER being below the NICE's threshold of £20,000-£30,000 per QALY, and both MNB and HNB having positive values (> 0).

Abstract

BACKGROUND The effectiveness of oral and intravenous iron supplementation in reducing the risk of mortality and hospitalizations in HF patients with iron deficiency is not well-established. METHODS A thorough literature search was conducted across 2 electronic databases (Medline and Cochrane Central) from inception through March 2021. RCTs assessing the impact of iron supplementation on clinical outcomes in iron deficient HF patients were considered for inclusion. Primary end-points included all-cause mortality and HF hospitalization. Evaluations were reported as odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. I(2) index was used to assess heterogeneity. RESULTS From the 2599 articles retrieved from initial search, 10 potentially relevant studies (n = 2187 patients) were included in the final analysis. Both oral (OR: 0.93; 95% CI: 0.08-11.30; p = 0.951) and intravenous (OR: 0.97; 95% CI: 0.73-1.29; p = 0.840) iron supplementation did not significantly reduce all-cause mortality. However, intravenous iron supplementation significantly decreased the rates of overall (OR: 0.52; 95% CI: 0.33-0.81; p = 0.004) and HF (OR: 0.42; 95% CI: 0.22-0.80; p = 0.009) hospitalizations. In addition, intravenous ferric carboxymaltose therapy significantly reduced the time to first HF hospitalization or cardiovascular mortality (RR = 0.70; 95% CI = 0.50-1.00; p = 0.048), but had no effect on time to first cardiovascular death (RR: 0.94; 95% CI: 0.70-1.25; p = 0.655). CONCLUSION Oral or intravenous iron supplementation did not reduce mortality in iron deficient HF patients. However, intravenous iron supplementation was associated with a significant decrease in overall and HF hospitalizations.

Abstract

BACKGROUND Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. OBJECTIVES (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. DESIGN A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. SETTING A total of 48 hospitals in the UK. PARTICIPANTS Women aged 16-39 years with early pregnancy bleeding. INTERVENTIONS Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. MAIN OUTCOME MEASURES The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. RESULTS A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (pound7655 vs. pound7572), with a mean cost difference of pound83 (adjusted mean difference pound76, 95% confidence interval - pound559 to pound711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as pound3305 per additional live birth at ≥ 34 weeks of gestation. CONCLUSIONS Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. TRIAL REGISTRATION Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 33. See the NIHR Journals Library website for further project information. Miscarriage is a common complication of pregnancy that affects one in five pregnancies. Several small studies have suggested that progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding. This research was undertaken to test whether or not progesterone given to pregnant women with early pregnancy bleeding would increase the number of live births when compared with placebo (dummy treatment). The women participating in the study had an equal chance of receiving progesterone or placebo, as determined by a computer; one group received progesterone (400 mg twice daily as vaginal pessaries) and the other group received placebo with an identical appearance. Treatment began when women presented with vaginal bleeding, were < 12 weeks of gestation and were found to have at least a pregnancy sac on an ultrasound scan. Treatment was stopped at 16 weeks of gestation, or earlier if the pregnancy ended before 16 weeks. Neither the participants nor their health-care professionals knew which treatment was being received. In total, 23,775 women were screened and 4153 women were randomised to receive either progesterone or placebo pessaries. Altogether, 2972 participants had a live birth after at least 34 weeks of gestation. Overall, the live birth rate in the progesterone group was 75% (1513 out of 2025 participants), compared with 72% (1459 out of 2013 participants) in the placebo group. Although the live birth rate was 3% higher in the progesterone group than in the placebo group, there was statistical uncertainty about this finding. However, it was observed that women with a history of one or more previous miscarriages and vaginal bleeding in their current pregnancy may benefit from progesterone. For women with no previous miscarriages, our analysis showed that the live birth rate was 74% (824 out of 1111 participants) in the progesterone group compared with 75% (840 out of 1127 participants) in the placebo group. For women with one or more previous miscarriages, the live birth rate was 75% (689 out of 914 participants) in the progesterone group compared with 70% (619 out of 886 participants) in the placebo group. The potential benefit appeared to be most strong for women with three or more previous miscarriages, who had a live birth rate of 72% (98 out of 137 participants) in the progesterone group compared with 57% (85 out of 148 participants) in the placebo group. Treatment with progesterone did not appear to have any negative effects. eng

Abstract

BACKGROUND Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Abstract

OBJECTIVE To compare postoperative blood loss after intravenous and intraarticular tranexamic acid injection in patients of bilateral total knee arthroplasty. METHODS This comparative randomised study was conducted at Ghurki Trust Teaching Hospital, Lahore, between July 2015 and January 2016, and comprised all patients admitted for bilateral total knee replacement. Patients were randomly divided into two equal groups. Group-A received intraarticular while Group-B received intravenous injection of 1.5 gmtranexamic acid. All data was analysed using SPSS 17. RESULTS The total 140 patients were divided into two equal groups of 70(50%) each. In Group-A there were 32(45.7%) males and 38(54.3%) females, while in Group-B, there were 28(40%) males and 42(60%) females. The mean ages were 64.39+/-9.07 years in Group-A and 63.30+/-9.51 years in Group B. Blood loss in Group-A was significantly lower than Group-B (p=0.01).. CONCLUSIONS Intraarticular administration of tranexamic acid was more effective than intravenous administration in terms of reducing blood loss.

Abstract

STUDY OBJECTIVE This study was designed to evaluate the therapeutic equivalence of balanced 6% hydroxyethyl starch (HES) 130/0.4 (Tetraspan) vs saline-based 6% HES 130/0.4 (Voluven) regarding the volume effect and the effect on acid-base status and renal functions in patients undergoing major urologic procedures. DESIGN Randomized comparative trial. SETTING Operating room and ward. PATIENTS Forty patients, American Society of Anesthesiologists statuses 1 and 2. INTERVENTION Patients were randomly allocated to receive either Voluven (n = 20) or Tetraspan (n = 20). MEASUREMENTS Hemodynamic variables. Laboratory variables in the form of arterial blood gases, serum chloride and sodium levels, hemoglobin level, international normalized ratio, and kidney and liver functions were measured after induction of anesthesia (T1), at the end of surgery (T2), and on the first postoperative day (T3). MAIN RESULTS Both groups were comparable regarding the total amount of study drugs and crystalloid consumption. No significant difference in hemoglobin levels between both groups, but there were significant differences between T1 and T2 hemoglobin within both groups and T3 hemoglobin in the Tetraspan group. Both groups were comparable regarding the renal functions, but there was a significant difference between T1 and T2 creatinine within both groups. No significant differences between both groups in liver functions and coagulation profile, but there were significant differences between values at T1, T2 and T3 within each group. Relative to baseline, both pH and bicarbonate decrease significantly in both groups. In the Voluven group, bicarbonate decreased significantly at the end of surgery relative to the Tetraspan group. Serum electrolytes did not vary between both groups. CONCLUSION Both balanced 6% HES 130/0.4 (Tetraspan) and saline-based 6% HES 130/0.4 (Voluven) were equally effective for hemodynamic stabilization of patients undergoing major urologic procedures without any significant impact on acid-base status or renal functions.

Abstract

BACKGROUND Acute depletion of plasma fibronectin levels has been reported during and after cardiopulmonary bypass; degradation of fibronectin by proteolytic enzymes has been suggested as one of the causes. This study was designed to assess the possible preservation of fibronectin levels by aprotinin during cardiopulmonary bypass. METHODS Plasma fibronectin levels were evaluated in 19 patients undergoing either elective coronary artery bypass grafting or a valvular heart operation. The study was conducted prospectively in a controlled, randomized, double-blinded manner. Nine test patients (group A) received intraoperative, intravenous administration of aprotinin; 10 control patients (group B) received equivalent volume of normal saline solution. Fibronectin levels were measured immediately after induction of anesthesia (as the baseline for the study) and at the following times: after 5 minutes on bypass, after 30 minutes on bypass, immediately before the start of rewarming, and after being off bypass for 5 minutes, but before protamine administration. RESULTS Both groups' basic characteristics were very similar. Group A patients were found to have significantly greater fibronectin levels than group B during and immediately after cardiopulmonary bypass (p < 0.002). CONCLUSIONS Administration of aprotinin intraoperatively appears to result in better preservation of fibronectin levels during cardiopulmonary bypass. Although the mechanism of action of aprotinin as a proteolytic inhibitor remains unclear, it has been suggested that it exerts an inhibiting effect on proteolytic enzymes by forming an aprotinin-proteinase complex. The clinical implications of the greater level of fibronectin achieved by the intraoperative use of aprotinin during cardiopulmonary bypass need further evaluation.