Open-label Randomized Clinical Trial Research Articles

Effectiveness of Prophylactic Intraperitoneal Mesh Implantation for Prevention of Incisional Hernia in Patients Undergoing Open Abdominal Surgery

Incisional hernia is a frequent complication after open abdominal surgery. Prophylactic mesh implantation in the onlay or sublay position requires dissection of the abdominal wall, potentially leading to wound-associated complications. To compare the incidence of incisional hernia among patients after prophylactic intraperitoneal mesh implantation with that among patients after standard abdominal closure. An open-label randomized clinical trial was performed in 169 patients undergoing elective open abdominal surgery from January 1, 2011, to February 29, 2014. Follow-up examinations were performed 1 year and 3 years after surgery. The study was conducted at Bern University Hospital, Bern, Switzerland, a referral center that offers the whole spectrum of abdominal surgical interventions. Patients with 2 or more of the following risk factors were included: overweight or obesity, diagnosis of neoplastic disease, male sex, or history of previous laparotomy. Patients were randomly assigned to prophylactic intraperitoneal mesh implantation or standard abdominal closure. Data were analyzed in August 2017. Intraperitoneal implantation of a polypropylene-polyvinylidene fluoride mesh with circumferential fixation. The primary end point was the incidence of incisional hernia 3 years after surgery. Secondary end points included mesh-related complications. After the exclusion of 19 patients, 150 patients (81 in the control group and 69 in the mesh group; mean [SD] age, 64.2 [11.1] years; 102 [68.0%] male) were studied. The cumulative incidence of incisional hernia was significantly lower in the mesh group compared with the control group (5 of 69 [7.2%] vs 15 of 81 [18.5%], log-rank test P = .03). Abdominal pain was observed in significantly more patients in the mesh group compared with the control group at 6 weeks (34 of 52 [65%] vs 26 of 59 [44%], P = .04) but not at 12 and 36 months postoperatively. No difference in surgical site infections was observed, but time to complete wound healing of surgical site infection was significantly longer in patients with mesh implantation (median [interquartile range], 8 [6-24] weeks compared with 5 [1-9] weeks; P = .03). Trunk extension was significantly decreased after mesh implantation compared with the control group (mean [SD], 1.73 [0.97] cm vs 2.40 [1.23] cm, P = .009). In patients at elevated risk for incisional hernia, prophylactic intraperitoneal mesh implantation reduces the incidence of hernia formation but with increased early postoperative pain and prolonged wound healing of surgical site infection. ClinicalTrials.gov Identifier: NCT01203553.

Freeze-dried bilberry (Vaccinium myrtillus) dietary supplement improves walking distance and lipids after myocardial infarction: an open-label randomized clinical trial

Bilberries, Vaccinium myrtillus, have a high content of phenolic compounds including anthocyanins, which could provide cardiometabolic health benefits following acute myocardial infarction (AMI). We hypothesized that standard medical therapy supplemented with freeze-dried bilberry after AMI would have a more beneficial effect on cardiovascular risk markers and exercise capacity than medical therapy alone. Patients were allocated in a 1:1 ratio within 24 hours of percutaneous coronary intervention in an 8-week trial either to V myrtillus powder (40 g/d, equivalent to 480 g fresh bilberries) and standard medical therapy or to a control group receiving standard medical therapy alone. High-sensitivity C-reactive protein and exercise capacity measured with the 6-minute walk test were the primary biochemical and clinical end points, respectively. Fifty subjects completed the study. No statistically significant difference in high-sensitivity C-reactive protein was detected between groups. The mean 6-minute walk test distance increased significantly more in the bilberry group compared to the control group: mean difference 38 m at follow-up (95% confidence interval 14-62, P = .003). Ex vivo oxidized low-density lipoprotein was significantly lowered in the bilberry group compared to control, geometric mean ratio 0.80 (95% confidence interval 0.66-0.96, P = .017), whereas total cholesterol and low-density lipoprotein cholesterol did not differ significantly between groups. Anthocyanin-derived metabolites in blood increased significantly in the bilberry group during the intervention and were different after 8 weeks between the bilberry group and control. Findings in the present study suggest that bilberries may have clinically relevant beneficial effects following AMI; a larger, double-blind clinical trial is warranted to confirm this.

Efficacy and Safety of Daflon® in the Treatment of Idiopathic Epistaxis.

Epistaxis is a very common ENT emergency with the idiopathic variety being the commonest type. Daflon® is a mixture of flavonoids with beneficial vascular effects that may help in the treatment of epistaxis. To assess the efficacy and safety of Daflon® in the treatment of idiopathic epistaxis. This is an open-label randomized clinical trial conducted on patients with idiopathic epistaxis comparing 1 group receiving Daflon® for 1 month and a second group receiving Daflon® for 3 months with a control group receiving nothing. The groups were evaluated regarding the number of visits to an emergency room and the number of patients needing cautery as indicators for the control of epistaxis. Also, the severity of epistaxis was assessed using epistaxis severity score (ESS) before and after treatment. We followed the patients for 1 year to determine the long-term effect of both drug protocols. The study included 450 patients distributed equally among the 3 study groups. The administration of Daflon® whether for 1 month or 3 months resulted in a significant improvement in our indicators for control of epistaxis including the number of patients visiting an emergency room and those needing cauterization after the failure of light nasal packing when compared with control group. Also, the severity of epistaxis as defined by the ESS was significantly less at the end of each treatment period and at 1-year follow-up when compared with the pretreatment severity. However, the use of Daflon® for 3 months was associated with a significantly more epistaxis control at 1-year follow-up when compared with the 1-month administration. Daflon® is a very effective and safe method for controlling idiopathic epistaxis. However, the daily use of Daflon® for 3 months has a more significant long-term beneficial effect than 1 month of use.

Economic analysis of acupuncture for migraine prophylaxis.

BackgroundAcupuncture has become a viable option for migraine prophylaxis in Europe; however, despite its wide use, more data on the short- and long-term cost-effectiveness are needed when considering the perspectives of a paying third-party, the patient, and of society in general. The aim was to evaluate the cost and effectiveness of adjuvant acupuncture to pharmacologic treatment vs pharmacologic treatment alone in migraine patients after a 3-month acupuncture course and a 6-month follow-up from all perspectives.MethodsThe study involved an open-label randomized clinical trial of patients receiving acupuncture (n=42), and a waiting list control group (n=44). The number of migraine days during the last 28 days, as well as direct and indirect costs were considered. The trial was registered under DRKS00009803.ResultsThe total cost per patient reached €696 vs €285 after 3 months of acupuncture and €66 vs €132 in the acupuncture and control groups after a 6-month follow-up, respectively (P=0.071). The trends observed in effectiveness and costs from all perspectives are discussed.ConclusionThe inclusion of acupuncture in health care results beneficial mainly for its observed trend in reduced losses of productivity and income, with the latter often exceeding the costs of acupuncture treatment. As such, acupuncture may be recommended as an adjuvant treatment in migraine prophylaxis to standard pharmacotherapy.

Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There are limited therapeutic management options. To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD. An open-label randomized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherlands. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m2. Follow-up of the 2.5-year trial ended in August 2017. Patients were randomized to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152). Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase. Secondary outcomes included change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]). Among the 309 patients who were randomized (mean [SD] age, 48.4 [7.3] years; 53.4% women), 261 (85.6%) completed the trial. Annual rate of eGFR decline for the lanreotide vs the control group was -3.53 vs -3.46 mL/min/1.73 m2 per year (difference, -0.08 [95% CI, -0.71 to 0.56]; P = .81). There were no significant differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P = .87), change in eGFR (-3.58 vs -3.45; difference, -0.13 mL/min/1.73 m2 per year [95% CI, -1.76 to 1.50]; P = .88), and change in quality of life (0.05 vs 0.07; difference, -0.03 units per year [95% CI, -0.13 to 0.08]; P = .67). The rate of growth in total kidney volume was lower in the lanreotide group than the control group (4.15% vs 5.56%; difference, -1.33% per year [95% CI, -2.41% to -0.24%]; P = .02). Adverse events in the lanreotide vs control group included injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%). Among patients with later-stage autosomal dominant polycystic kidney disease, treatment with lanreotide compared with standard care did not slow the decline in kidney function over 2.5 years of follow-up. These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease. ClinicalTrials.gov Identifier: NCT01616927.

COST-EFFECTIVENESS OF HOME OXYGEN THERAPY-HOME MECHANICAL VENTILATION (HOT-HMV) FOR TREATMENT OF COPD WITH CHRONIC HYPERCAPNIC RESPIRATORY FAILURE FOLLOWING AN ACUTE EXACERBATION OF COPD IN THE US

SESSION TITLE: Improving Care in COPD SESSION TYPE: Original Investigations PRESENTED ON: 10/08/2018 01:30 PM - 02:30 PM PURPOSE: In the UK trial of HOT-HMV, delayed time to readmission was reported in patients (pts) with persistent hypercapnia following a life-threatening exacerbation of COPD requiring acute non-invasive ventilation (NIV) (Murphy et al., JAMA 2017). The health economic impact of HOT-HMV in the US has been previously reported using costs for a respiratory assist device with a -$50,856 /quality-adjusted life year (QALY) (Criner et al ATS 2018). The current study reports the incremental cost-effectiveness (CE) of HOT-HMV with a home ventilator device. METHODS: The analysis included pt-level use of equipment (O2 concentrator, home NIV device, maintenance and support), from the intent-to-treat analysis of an open-label parallel-group randomized clinical trial. Pts with a hospitalization due to a COPD exacerbation requiring acute NIV with persistent hypercapnia 2-4 weeks following resolution of respiratory acidosis were enrolled. Pts in the control arm were permitted to have HMV added to HOT if the primary end-point (hospital readmission) was met & if pre-set safety criteria were breached (e.g. persistent acidosis & inability to wean from NIV). The analysis included medical resource utilization (MRU) of patient-level evaluation of equipment (oxygen concentrator & ventilator NIV device, including maintenance & support), patient-reported medication, physician office visits, & hospital admissions due to exacerbations. Trial data were used to develop an economic model from the US payer perspective. Costs were calculated by multiplying observed MRU by standard unit costs (2018$) & summed at the pt level. QALYs were measured based on patient health utilities calculated with US coefficients & EuroQOL EQ-5D data from the trial. One-way sensitivity and bootstrap analyses with 1,000 iterations were completed. RESULTS: 28/59 HOT pts & 36/57 HOT-HMV pts completed the 12-month study; 17 pts allocated to HOT received additional HMV. Rehospitalization w/i 30 days was 58.3% lower in the intervention group. The base-case incremental cost/QALY gained was $24,375, suggesting HOT-HMV is cost-effective with the higher cost of a home ventilator. Total costs were $32,330 for HOT-HMV & $30,447 for HOT alone. HOT-HMV patient costs were $11,973 for devices, $10,910 for doctor visits, $758 for medication, & $8,689 for exacerbations; corresponding costs for HOT alone were $3,383, $15,179, $1,087, & $10,798. One-way sensitivity analysis suggests that the home ventilator device cost has the greatest impact on cost/QALY. A bootstrap analysis indicates the probability for HOT-HMV being more expensive & more effective is 60.4%. CONCLUSIONS: These data support the cost-effectiveness of HOT-HMV using a home ventilator device for treatment in the U.S. CLINICAL IMPLICATIONS: In addition to the clinical effectiveness of HOT-HMV as previously reported, these data support the cost effectiveness of HOT-HMV using a home ventilator device for treatment. DISCLOSURES: no disclosure on file for Bernd Brüggenjürgen; Advisory Committee Member relationship with GSK, BI, Chiesi, Pulmonx, BTG, Novartis, Mereo Please note: $1001 - $5000 Added 03/01/2018 by Gerard Criner, source=Web Response, value=Consulting fee Consultant relationship with GSK, BI, novartis, Mereo, Prometic, Pulmonx, BTG, Pneumrx Please note: $1001 - $5000 Added 06/01/2018 by Gerard Criner, source=Web Response, value=Consulting fee Consultant relationship with Resmed and Philips Please note: >$100000 Added 03/16/2018 by Lauren Fusfeld, source=Web Response, value=Consulting fee Employee relationship with Boston Healthcare Associates Please note: >$100000 Added 03/03/2018 by Thomas Goss, source=Web Response, value=Grant/Research SupportRemoved 03/03/2018 by Thomas Goss, source=Web Response Employee relationship with Boston Healthcare Associates Please note: >$100000 Added 03/03/2018 by Thomas Goss, source=Web Response, value=SalaryRemoved 03/03/2018 by Thomas Goss, source=Web Response Consultant relationship with ResMed Please note: $20001 - $100000 Added 03/03/2018 by Thomas Goss, source=Web Response, value=Grant/Research Support Consultant relationship with Philips Respironics Please note: $20001 - $100000 Added 03/03/2018 by Thomas Goss, source=Web Response, value=Grant/Research Support Consultant relationship with Resmed Please note: $5001 - $20000 Added 03/05/2018 by Qing Gu, source=Web Response, value=Grant/Research Support no disclosure on file for Nicholas Hart; Speaker/Speaker's Bureau relationship with Philips respironics Please note: $1-$1000 Added 03/15/2018 by Patrick Murphy, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with ResMed Please note: $1-$1000 Added 03/15/2018 by Patrick Murphy, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Breas Please note: $1-$1000 Added 03/15/2018 by Patrick Murphy, source=Web Response, value=Honoraria

Cost-consequence analysis of fluticasone furoate/vilanterol 92/22 mcg for the management of COPD in the Spanish NHS.

ObjectivesThe Salford Lung Study in Chronic Obstructive Pulmonary Disease (SLS COPD) is a 12-month, open-label randomized clinical trial comparing clinical effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol (FF/VI) 92/22 mcg with continuing usual care (UC) in patients with COPD followed in primary care in the UK. The objective of this analysis is to estimate the economic impact of these results when applied to Spain.Materials and methodsAn Excel-based cost–consequence model with a one-year time horizon was populated with SLS COPD results, adopting the Spanish National Health System (NHS) perspective. Patients analyzed were diagnosed COPD patients ≥40 years old, currently managed with maintenance treatment and with a history of exacerbations (total number estimated from Spanish data). Mean least squares annual rates of moderate/severe exacerbations after 1 year for the intention-to-treat population from SLS COPD were included in the model (1.50 [FF/VI] and 1.64 [UC]); serious adverse events were excluded from the analysis as no differences between treatment arms were found. Medication and exacerbation management costs in euros were estimated from Spanish public sources for 2016. Model base-case analysis assumed an increased usage of FF/VI from 4% to 10% within 1 year, and a 100% proportion of days covered with study medications. Deterministic sensitivity analyses were performed for mitigating uncertainty.ResultsAt base case, within 50,522 COPD patients analyzed, substitution of UC with FF/VI 92/22 mcg was associated with reduced medication and exacerbation management costs, leading to potential total annual savings of €353,623. Deterministic sensitivity results ranged from €218,333 up to €1,532,366 potential cost savings associated with FF/VI, showing the robustness of base-case results.ConclusionThe decreased rate of exacerbations with FF/VI 92/22 mcg compared with UC observed in SLS COPD could be translated into potential health care savings for the Spanish NHS. These results may be useful to inform decision-making processes.

Effect of extra-amniotic Foley\u2019s catheter and vaginal misoprostol versus vaginal misoprostol alone on cervical ripening and induction of labor in Kenya, a randomized controlled trial

BackgroundThe safest, most effective and fastest combined approaches to induction of labor is unknown. In an open-label randomized clinical trial we evaluated the efficacy of combination of extra-amniotic Foley’s catheter and vaginal misoprostol compared to vaginal misoprostol alone for cervical ripening and induction of labor on the incidence of failed induction, induction-to-delivery interval and adverse maternal and perinatal outcomes.MethodsPregnant women at gestational age of 28 weeks or greater admitted at Kenyatta National Hospital, Kenya for induction of labor were enrolled then randomized to either a combination of extra-amniotic Foley’s catheter inflated by 30 cm3 of normal saline and 25 micrograms of vaginal misoprostol or 25 micrograms of vaginal misoprostol alone. Women underwent 6 hourly reviews and additional misoprostol inserted if required. The primary outcome was incidence of failed induction. Secondary outcomes were induction-to-delivery interval and adverse maternal and perinatal outcomes. We conducted an intent-to-treat analysis and compared means or medians using t-test or Wilcoxon rank, proportions using Chi-square or Fishers test as appropriate. Induction-to-delivery interval were compared using the log-rank test. P-values of < 0.05 and 95% confidence intervals that excluded the null were considered statistically significant.ResultsBetween February and May 2016, we enrolled 180 of 237 pregnant women admitted for induction of labor and randomized them to either a combination of extra-amniotic Foley’s catheter and vaginal misoprostol (n = 90) or vaginal misoprostol alone (n = 90). The socio-demographic and obstetric characteristics were similar between the two groups. Failed induction rates were lower but not statistically significant following combined extra-amniotic Foley’s catheter and vaginal misoprostol (8.9%) versus vaginal misoprostol alone (11.1%). The mean induction-to-delivery time was 4.8 h shorter in the combined extra-amniotic Foley’s catheter and vaginal misoprostol (mean 18.9, standard deviation (SD) 7.2 h) compared to misoprostol only group (mean 14.1, SD 6.9 h) (log-rank test, p < 0.001). Maternal and perinatal complications were similar between the two groups.ConclusionsExtra-amniotic Foley’s catheter and vaginal misoprostol for cervical ripening and induction of labor did not significantly lower the incidence of failed induction but safely shortened induction-to-delivery time compared to vaginal misoprostol only.Trial registrationTrial was retrospectively registered on 14–03-2016 PACTR201604001535825.

ADHESION BARRIER GEL ANTIADGEZIN FOR DEGENERATIVE LUMBAR SPINE DISEASE

Objective. To assess the effectiveness of the application of adhesion barrier gel Antiadgezin to prevent the development of cicatricial adhesive process and its complications in the spinal canal after decompression surgery for degenerative disease in the lumbar spine. Material and Methods . An open-label comparative randomized prospective clinical trial was conducted. The study involved 30 patients with degenerative lumbar spine disease who underwent decompression surgery. Patients were divided into two groups: in Group 1, gel Antiadgesin was injected during the spinal canal decompression, and in Group 2, the saline solution was injected. The severity of adhesive process was assessed according to MRI findings, and the severity of the pain syndrome and the degree of vital activity limitation were assessed by VAS and the Oswestry questionnaire in 2 weeks, 2 months and 1 year after surgery. Results. Application of gel Antiadgesin allows reducing the probability of cicatricial process development in the spinal canal up to 35 % in comparison with the control group. The intensity of the cicatricial adhesive process development decreases by more than 3 times with the application of gel Antiadgesin. Reduction of pain syndrome according to VAS and restoration of physical activity are significantly more pronounced during the first weeks in Group 1. Infectious complications or allergic reactions in the study groups were not noted. Conclusion. The use of adhesive barrier gel Antiadgesin during surgery reduces the likelihood of cicatricial adhesive process development in the spinal canal, which allows decreasing pain intensity and preventing disability in the postoperative period.

Endoscopic push-through technique compared to microscopic underlay myringoplasty in anterior tympanic membrane perforations.

Microscopic myringoplasty is the most frequently performed procedure for repairing tympanic membrane perforations. The endoscopic transcanal approach bypasses the narrow ear canal segment and provides a wider view. An open-label randomised clinical trial was conducted on 56 patients with small anterior tympanic membrane perforations. Perforations were repaired with an endoscopic push-through technique (n = 28) or a microscopic underlay technique (n = 28). Follow up was conducted using endoscopic examination and pure tone audiometry three months' post-operatively. Graft success rate was 92.9 per cent in the endoscopic group versus 85.7 per cent in the microscopic group. The corresponding pre-operative mean air-bone gaps were 17.4 dB and 18.5 dB, improving to 6.1 dB and 9.3 dB post-operatively (p > 0.05). Mean air-bone gap closure was 11.4 dB in the endoscopic group and 9.2 dB in the microscopic group (p > 0.05). Mean operative time and estimated blood loss were 37.0 minutes and 29 ml in the endoscopic group, versus 107 minutes and 153 ml in the microscopic group (both p < 0.05). The endoscopic push-through technique for anterior tympanic membrane perforations is as effective as microscopic underlay myringoplasty; furthermore, it is less invasive and takes less operative time.

Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes

Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease. To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion. Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses. The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan. A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48). Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment. ClinicalTrials.gov Identifier: NCT01176565.

Prevention of preterm birth with pessary in singletons (PoPPS): randomized controlled trial.

To determine if pessary use prevents preterm birth (PTB) in women with singleton pregnancy, with short cervical length (CL) measured on transvaginal sonography (TVS) and without prior spontaneous PTB (sPTB). This was an open-label multicenter randomized trial of asymptomatic women presenting at 18 + 0 to 23 + 6 weeks' gestation with a singleton pregnancy, CL ≤ 25 mm on TVS and no prior sPTB. sPTB included those with spontaneous onset of labor and those with rupture of membranes prior to labor. Subjects were randomized to receive either a Bioteque cup pessary or no pessary. Pessaries were inserted by trained maternal-fetal medicine staff. Vaginal progesterone was recommended to women with CL ≤ 20 mm. The primary outcome was PTB < 37 weeks. A sample size of 121 women in each group (n = 242) was needed to detect a reduction in the primary outcome from 30% in the no-pessary group to 15% in the pessary group. The trial was stopped early before complete enrollment. Between 17 March 2014 and 29 July 2016, 17 383 women underwent CL measurement on TVS. Of these, 422 (2.4%) had CL ≤ 25 mm and 391 (92.7%) met the full eligibility criteria, of which 122 (31.2%) agreed to randomization. Sixty-one (50%) women were randomized to the pessary group and 61 (50%) to the no-pessary group. Baseline characteristics were similar between the groups. There were no significant differences between the pessary and no-pessary groups in the rate of PTB < 37 weeks (43% vs 40%; relative risk 1.09; 95% CI, 0.71-1.68) or in secondary outcomes, such as rate of PTB < 34 weeks, rate of PTB < 28 weeks, gestational age at delivery, birth weight and rate of composite adverse neonatal outcome. Cervical pessary use was not associated with prevention of PTB in women with a singleton pregnancy, short CL on TVS and no prior sPTB in this small, underpowered randomized controlled trial. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients — Open-labeled randomized clinical trial

PurposeTo investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). Materials and MethodsThis open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. ResultsThe adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. ConclusionsAdjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort.

Studi Klinis Ramuan Jamu Antihipertensi pada Pasien Hipertensi Derajat I

Hypertension is a risk factor for cardiovascular disease. Hypertension is one of the main causes of high mortality and morbidity in Indonesia. Utilization of medicinal herbs is an alternative for the treatment of hypertension. The study aimed to determine the efficacy of the herbs combination compared to HCT and evaluated the safety for hypertention stage I. This research method using an open-label randomized clinical trials with intervention for 56 days. Measurement of day-56 (D-56) showed that herbs decreased sistolic blood pressure to 130.15 + 17.59 mmHg and diastolic at 83.82 + 9.53 mmHg. There was a significant decrease p = 0.000 (p 0.05), with p mean systolic blood pressure (p = 0.370) and mean diastolic blood pressure (p = 0.412). Liver function parameters (SGOT, SGPT) and renal function (urea, creatinine) is still in normal range at the end of intervention. This study showed that herbs combination was an equally effective compared to HCT and safe for hypertension stage

Cisplatin Chemoradiotherapy vs Radiotherapy in FIGO Stage IIIB Squamous Cell Carcinoma of the Uterine Cervix

The evidence for concurrent chemoradiotherapy (CT-RT) in International Federation of Gynecology and Obstetrics (FIGO) stage IIIB squamous cell carcinoma of the uterine cervix is not robust. This study reports the final results of a randomized clinical trial of concurrent cisplatin-based CT-RT and radiotherapy alone (RT) in women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix. To investigate the benefit of concurrent CT-RT in FIGO stage IIIB squamous cell carcinoma of the uterine cervix. This phase 3 open-label randomized clinical trial accrued 850 women in Mumbai, India, between July 7, 2003, and September 22, 2011. Of 2121 screened, 850 women with FIGO stage IIIB squamous cell carcinoma of the uterine cervix suitable for concurrent cisplatin chemotherapy were randomly assigned to CT-RT and RT using block randomization (1:1). The data were updated for a minimum follow-up period of 5 years until December 2016. The final analyses were performed in February and March 2017. This single-institution study was conducted at a tertiary cancer center setting. Randomization to receive RT (RT arm), comprising a combination of external beam RT (50 Gy in 25 fractions over 5 weeks) and brachytherapy, or to receive in addition to the same RT concurrent weekly cisplatin chemotherapy (40 mg/m2 per week) (CT-RT arm). The primary end point was 5-year disease-free survival (DFS), defined as the time between the date of randomization and the date of any recurrence or death (whichever occurred first) in the intent-to-treat population. This trial included 424 women assigned to CT-RT (mean [SD] age, 49.4 [7.9] years) and 426 women assigned to RT (mean [SD] age, 49.3 [7.9] years). At a median follow-up of 88 months (interquartile range, 61.3-113.1 months), there were 222 recurrences and 213 deaths in the CT-RT arm and 252 recurrences and 243 deaths in the RT arm. The 5-year DFS was significantly higher in the CT-RT arm (52.3%; 95% CI, 52.2%-52.4%) compared with the RT arm (43.8%; 95% CI, 43.7%-43.9%), with a hazard ratio for relapse or death of 0.81 (95% CI, 0.68-0.98) (P = .03). Similarly, the 5-year overall survival (OS) was significantly higher in the CT-RT arm (54.0%; 95% CI, 53.9%-54.1%) compared with the RT arm (46.0%; 95% CI, 45.9%-46.1%), with a hazard ratio for death of 0.82 (95% CI, 0.68-0.98; P = .04). After adjusting for prognostic factors, CT-RT continued to be significantly superior to RT for DFS and OS. There was a higher incidence of acute hematological adverse effects in the CT-RT arm. Chemoradiotherapy using weekly cisplatin results in significantly better DFS and OS compared with RT in women with stage IIIB squamous cell carcinoma of the uterine cervix. This study provides level 1 evidence in the largest clinical trial reported so far in favor of concurrent weekly cisplatin chemotherapy in this setting. clinicaltrials.gov Identifier: NCT00193791.

Topical lidocaine-prilocaine cream versus lidocaine infiltration for pain relief during repair of perineal tears after vaginal delivery: randomized clinical trial

Objective: The current study aims to compare the analgesic effect of lidocaine-prilocaine (LP) cream with lidocaine infiltration during repair of perineal tears after vaginal delivery.Materials and methods: A single center open-labeled randomized clinical trial was carried out in a tertiary University Hospital between October 2016 and May 2017 (Clinical Trials.Gov: NCT02883179). We included parous women, who delivered at gestational age >37 weeks with first- or second-degree perineal tears. The participants were randomized in a 1:1 ratio to either lidocaine infiltration (Group I); or application of LP cream (Group II) for pain relief during perineal repair. The primary outcome was the difference in mean pain score during perineal repair. Secondary outcomes included the participants’ satisfaction, the need for additional anesthesia, the duration of perineal repair, and the rate of adverse effects of both medications.Results: The study included 144 participants randomized to both groups. The mean pain score during perineal repair was significantly lower in the LP cream group (3.86 ± 1.59) than the lidocaine infiltration group (5.99 ± 1.47) [p = .001]. The duration of repair was significantly shorter in the LP group than the lidocaine infiltration group (6.37 ± 3.68 versus 8.17 ± 2.75 min, respectively, p = .001). The need for additional anesthesia was quite similar in both groups (p = .371). More women in the LP cream group were satisfied than the other group with statistical significant difference (76.4 versus 30.6%, p = .000). No difference between side effects in both groups (p = .171)Conclusions: Topical application of lidocaine-prilocaine cream is an effective analgesic during repair of perineal tears with no harmful side effects.

Antibiotic stewardship program in Intensive Care Unit: First report from Iran.

Introduction:Few data regarding antibiotic stewardship programs in critically ill patients are available. In the present study, the consequence of changing an empirical antibiotic regimen from a carbapenem (meropenem) to a noncarbapenem antibiotic (piperacillin-tazobactam) was evaluated in critically ill patients with a suspicion of sepsis.Methods:This open-label randomized clinical trial was conducted during May 2015–January 2017 at the general Intensive Care Unit of the Imam Khomeini Hospital Complex, Tehran, Iran. In this study, a carbapenem (meropenem) or a noncarbapenem (piperacillin-tazobactam) antibiotic was considered as an empirical antibiotic regimen in 100 critically ill patients with a suspicion of sepsis. Clinical response and bacterial eradication were defined as primary and secondary outcomes of the study, respectively. Chi-square, Mann–Whitney, and independent sample t-tests were used for comparing variables between the groups. ANOVA was used to compare changes in the mean differences of parameters between the groups. Meaningful difference was indicated as P ≤ 0.05.Results:During the first 72 h of the antibiotic course, the number of patients with clinical response was comparable between piperacillin-tazobactam and meropenem groups (21 [42%] and 25 [50%], respectively, P = 0.31). Also, at this time, microbial eradication occurred in 13 (54.16%) and 9 (40.90%) patients in piperacillin-tazobactam and meropenem groups, respectively (P = 0.67).Conclusions:Using a carbapenem (meropenem) instead of a noncarbapenem (piperacillin-tazobactam) as an empirical antibiotic regimen did not affect clinical response and bacterial eradication rates in critically ill patients with a suspicion of sepsis.

COMPARATIVE STUDY OF COMMONLY PRACTICED ATROPINIZATION REGIMENS IN ACUTE ORGANOPHOSPHORUS COMPOUND POISONING

Aim of the study: Effect of atropinization with different methods. Outcomes in terms of duration of hospital stay and patients recovery. Methodology: An open-label randomized clinical trial was conducted in, Shri B M Patil Medical College Hospital and Research Centre, Vijayapura, Karnataka. 108 individuals with OPC poisoning .We compared two groups that used a titrated dosing protocol based on a structured monitoring sheet for atropine infusion with another group using an ‘ad hoc’ regime. The aim was to compare the efficacy and safety of conventional bolus doses with individualized incremental doses of atropine for atropinization followed by continuous atropine infusion for management of OPC poisoning. Result: Out of 108 patients, 54 patients received conventional bolus dose atropine (group A) and 54 patient received rapidly incremental doses of atropine followed by infusion (group B).36 subjects analyzed in group A and 32 in group B for moderate to severe poisoning. The mortality in group A was 11.1%(4/36) and in group B was 6.3%(2/32).The mean duration of atropinization in group A was 5.8hrs (348) in minutes compared to time 26.9minutes for group B. Conclusion: Administration of atropine using a fixed algorithm is easy and effective in providing the atropine requirement in management of early phase of acute OPC poisoning. Rapid incremental dose atropinization followed by atropine infusion reduces mortality and morbidity from OPC poisoning and shortens the length of hospital stay and early recovery .Incremental atropine and infusion should become the treatent of choice for OPC poisoning. Keywords: Organophosphate compound; Atropine toxicity; Organophosphorus poisoning; Atropinization protocols.

Nevirapine- versus Efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and Tuberculosis infections in India: a multi-centre study

BackgroundAccording to World Health Organization (WHO) guidelines, which have also been adopted by the National AIDS Control Organization (NACO), India, Efavirenz-based Anti-Retroviral Therapy (ART) is better in Human-Immunodeficiency-Virus (HIV)-infected patients who are also being treated with Rifampicin-based Anti-Tuberculous Therapy (ATT). However, Efavirenz is much more expensive. We hypothesize that Nevirapine is a cheaper alternative that possesses equal efficacy as Efavirenz in HIV-Tuberculosis (TB) co-infected patients.MethodsA parallel open-label randomized clinical trial was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi and National AIDS Research Institute (NARI), Pune. Those who were ART-naïve and co-infected with TB were randomized to receive either Nevirapine (Group 1)- or Efavirenz (Group 2)-based ART along with Rifampicin-based ATT. ATT was begun first in ART-naïve patients according to the NACO guidelines, with a median of 27 days between ATT and ART in both groups. The primary endpoint was a composite unfavourable outcome (death and/or ART failure) at 96 weeks, and the secondary outcome was successful TB treatment at 48 weeks.ResultsA total of 284 patients (mean age 36.7 ± 8.1 years) were randomized in a 1:1 ratio to receive either Nevirapine (n = 144)- or Efavirenz (n = 140)-based ART after a median ATT-ART gap of 27 days. The median CD4 count was 105 cells/μl, with a median viral load of 820,200 copies/μl and no significant difference between the groups. Composite unfavourable outcomes were reported in 49 patients in the Nevirapine group and 51 patients in the Efavirenz group (35.3% vs. 36.9%; hazard ratio, 0.95, 95% confidence interval (CI), 0.63,1.43, adjusted). There was no difference in successful TB treatment outcome between the groups (71.5% vs. 65.6%, 95% CI -3.8,17.9, adjusted). The results were similar, showing no difference between the groups in the two centres of the study after adjusting for disease stage.ConclusionsComposite unfavourable outcome in HIV-TB co-infected patients who were ART-naïve showed no statistically significant difference in the Nevirapine or Efavirenz groups.. Therefore, Nevirapine-based ART is a reasonable alternative to Efavirenz in resource-limited settings. However, multi-centric studies with larger sample sizes are required to confirm these findings.Trial registrationNCT01805258 (Retrospectively registered on March 6, 2013) Date of registration: March 2013.

A Fully Automated Web-Based Program Improves Lifestyle Habits and HbA1c in Patients With Type 2 Diabetes and Abdominal Obesity: Randomized Trial of Patient E-Coaching Nutritional Support (The ANODE Study).

BackgroundThe prevalence of abdominal obesity and type 2 diabetes mellitus (T2DM) is a public health challenge. New solutions need to be developed to help patients implement lifestyle changes.ObjectiveThe objective of the study was to evaluate a fully automated Web-based intervention designed to help users improve their dietary habits and increase their physical activity.MethodsThe Accompagnement Nutritionnel de l’Obésité et du Diabète par E-coaching (ANODE) study was a 16-week, 1:1 parallel-arm, open-label randomized clinical trial. Patients with T2DM and abdominal obesity (n=120, aged 18-75 years) were recruited. Patients in the intervention arm (n=60) had access to a fully automated program (ANODE) to improve their lifestyle. Patients were asked to log on at least once per week. Human contact was limited to hotline support in cases of technical issues. The dietetic tool provided personalized menus and a shopping list for the day or the week. Stepwise physical activity was prescribed. The control arm (n=60) received general nutritional advice. The primary outcome was the change of the dietary score (International Diet Quality Index; DQI-I) between baseline and the end of the study. Secondary endpoints included changes in body weight, waist circumference, hemoglobin A1c (HbA1c) and measured maximum oxygen consumption (VO2 max).ResultsThe mean age of the participants was 57 years (standard deviation [SD] 9), mean body mass index was 33 kg/m² (SD 4), mean HbA1c was 7.2% (SD 1.1), and 66.7% (80/120) of participants were women. Using an intention-to-treat analysis, the DQI-I score (54.0, SD 5.7 in the ANODE arm; 52.8, SD 6.2 in the control arm; P=.28) increased significantly in the ANODE arm compared to the control arm (+4.55, SD 5.91 vs -1.68, SD 5.18; between arms P<.001). Body weight, waist circumference, and HbA1c changes improved significantly in the intervention.ConclusionsAmong patients with T2DM and abdominal obesity, the use of a fully automated Web-based program resulted in a significant improvement in dietary habits and favorable clinical and laboratory changes. The sustainability of these effects remains to be determined.Trial RegistrationClinicalTrials.gov NCT02343107; http://clinicaltrials.gov/ct2/show/NCT02343107 (Archived by WebCite at http://www.webcitation.org/6uVMKPRzs)