A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition-Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India

Purpose. Advanced cancer patients with disease progression develop cachexia. Nevertheless, cancer patients at nutritional risk have shown improved body weight and quality of life with oral nutritional supplements. Method. This was a randomized controlled trial in adult female cancer patients (n = 63) attending palliative clinics, with symptoms of cachexia. Eligible patients were randomly distributed into control (n = 33) and intervention (n = 30) groups. Both groups were provided with nutritional and physical activity counseling, but the intervention group received an additional 100 g of Improved Atta (IAtta) for 6 months daily consumption. This study was designed to assess the efficacy of IAtta (with counseling) in enhancing the health status of cachexic patients. Anthropometric measurements, dietary intake, physical activity level and quality of life parameters were assessed at baseline, after 3 months, and at the end of 6 months. Results. Patients in the control group (n = 15) had significantly decreased body weight (P = .003), mid–upper-arm circumference (P = .002), and body fat (P = .002) by the end of intervention. A trend of body weight gain in the intervention group (n = 17; P = .08) and significant increase of body fat (P = .002) was observed; moreover, patients reported a significant improvement in fatigue (P = .002) and appetite scores (P = .006) under quality-of-life domains at the end of intervention. Conclusions. Embedding a nutrition-sensitive intervention ( IAtta ) within Indian palliative care therapy may improve quality of life and stabilize body weight in cancer cachexia patients.

Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).

PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. RESULTS: One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

A randomized controlled trial of an early-intervention, computer-based literacy program to boost phonological skills in 4- to 6-year-old children

Background: Many school-based interventions are being delivered in the absence of evidence of effectiveness (Snowling & Hulme, 2011, Br. J. Educ. Psychol., 81, 1).Aim: This study sought to address this oversight by evaluating the effectiveness of the commonly used the Lexia Reading Core5 intervention, with 4- to 6-year-old pupils in Northern Ireland.Sample: A total of 126 primary school pupils in year 1 and year 2 were screened on the Phonological Assessment Battery 2nd Edition (PhAB-2). Children were recruited from the equivalent year groups to Reception and Year 1 in England and Wales, and Pre-kindergarten and Kindergarten in North America.
Methods: A total of 98 below-average pupils were randomized (T0) to either an 8-week block (inline image = 647.51 min, SD = 158.21) of daily access to Lexia Reading Core5 (n = 49) or a waiting-list control group (n = 49). Assessment of phonological skills was completed at post-intervention (T1) and at 2-month follow-up (T2) for the intervention group only.
Results: Analysis of covariance which controlled for baseline scores found that the Lexia Reading Core5 intervention group made significantly greater gains in blending, F(1, 95) = 6.50, p = .012, partial η2 = .064 (small effect size) and non-word reading, F(1, 95) = 7.20, p = .009, partial η2 = .070 (small effect size). Analysis of the 2-month follow-up of the intervention group found that all group treatment gains were maintained. However, improvements were not uniform among the intervention group with 35% failing to make progress despite access to support. Post-hoc analysis revealed that higher T0 phonological working memory scores predicted improvements made in phonological skills.
Conclusions: An early-intervention, computer-based literacy program can be effective in boosting the phonological skills of 4- to 6-year-olds, particularly if these literacy difficulties are not linked to phonological working memory deficits.

Interventions to Promote Follow-up After Trabeculectomy Surgery in Rural Southern China: A Randomized Clinical Trial.

Importance:

Follow-up after trabeculectomy surgery is important to surgical success, but little is known about the effect of interventions on improving follow-up in low-resource areas.

Objective:

To examine whether text message reminders and free eye medications improve follow-up after trabeculectomy in rural southern China.

Design, Setting, and Participants:

This randomized clinical trial studied 222 consecutive patients undergoing trabeculectomy from October 1, 2014, through November 31, 2015, at 4 rural hospitals in Guangdong and Guangxi Provinces, China. Data from the intention-to-treat population were analyzed.

Interventions:

Patients undergoing trabeculectomy were randomized (1:1) to receive text message reminders 3 days before appointments at 1 and 2 weeks and 1 month after surgery and free topical corticosteroid medication (US$5.30) at each visit or to standard follow-up without reminders or free medication.

Main Outcomes and Measure:

Follow-up at 1 month postoperatively.

Results:

Among 222 eligible patients, 13 (5.9%) refused and 209 (94.1%) were enrolled, with 106 (50.7%) randomized to the intervention group (mean [SD] age, 64.4 [12.7] years; 56 women [52.8%]) and 103 (49.3%) to the control group (mean [SD] age, 63.0 [12.7] years; 53 women [51.5%]). A total of 6 patients (2.9%) were unavailable for follow-up. Attendance at 1 month for the intervention group (59 of 102 [57.8%]) was significantly higher than for the control group (34 of 101 [33.7%]) (unadjusted relative risk [RR], 1.72; 95% CI, 1.13-2.63; P = .01). Factors associated with 1-month attendance in multiple regression models included intervention group membership (RR, 1.65; 95% CI, 1.08-2.53; P = .02) and being told to return for suture removal (RR, 1.80; 95% CI, 1.06-3.06; P = .03). One-month attendance among controls not told about suture removal was 3 of 31 (9.7%), whereas it was 44 of 68 (64.7%) among the intervention group with suture removal (unadjusted RR, 6.69; 95% CI, 2.08-21.6; P = .001).

Conclusions and Relevance:

In this setting, low-cost interventions may significantly improve postoperative follow-up after glaucoma surgery, a potential opportunity for interventions known to improve surgical success.

Stapled haemorrhoidopexy vs. Milligan-Morgan haemorrhoidectomy for grade III haemorrhoids: a randomized clinical trial

The aim of this double blind randomized clinical trial was to compare the short-term and long-term outcomes of stapled haemorrhoidopexy (SH group) performed using a circular stapler with that of the Milligan-Morgan haemorrhoidectomy (MMH group). A total of 79 consecutive patients with grade III haemorrhoids were randomized into two groups treated with SH (n. 39) and MMH (n. 40). The outcomes of the procedures were evaluated postoperatively and over a follow-up period of minimum 2 years. Patients undergoing the SH procedure showed greater short term advantages than MMH group with reduced pain, shorter length of hospital stay, earlier return to work and high patient satisfaction. Long-term follow-up has indicated more favourable results in MMH group in terms of resumption of symptoms with absence of residual prolapse and risk of recurrence of prolapse. At two years follow-up recurrent prolapse was confirmed in six patients of SH group (13%) whereas in none of the MMH group. At six months follow-up there weren’t significant difference in the mean satisfaction score for the two groups. At two years the mean satisfaction score was higher in the MMH group vs SH group. Seven patients in the SH group needed a reoperation whereas none in MMH group. From January 2009, in our Surgery Unit the patients are always informed about a higher recurrence rate of SH and we perform this technique only when the patient choices to accept this risk to take advantage of the short-term benefits of this procedure.

Clinical trial designs of new medicinal products for treating schizophrenia: discussion of EMA's Guideline and a Better Long Term Trial Design

Background and Objectives: Schizophrenia is a severe chronic disease. Endpoint variables lack objectivity and the diagnostic criteria have evolved with time. In order to guide the development of new drugs, European Medicines Agency (EMA) issued a guideline on the clinical investigation of medicinal products for the treatment of schizophrenia. Methods: Authors reviewed and discussed the efficacy trial part of the Guideline. Results: The Guideline divides clinical efficacy trials into short-term trials and long-term trials. The short-term three-arm trial is recommended to replace the short-term two-arm active-controlled non-inferiority trial because the latter has sensitivity issues. The Guideline ultimately makes that three-arm trial a superiority trial. The Guideline discusses four types of long-term trial designs. The randomized withdrawal trial design has some disadvantages. Long-term two-arm active-controlled non-inferiority trial is not recommended due to the sensitivity issue. Extension of the short-term trial is only suitable for extension of the short-term two-arm active-controlled superiority trial. The Guideline suggests that a hybrid design of a randomized withdrawal trial incorporated into a long-term parallel trial might be optimal. However, such a design has some disadvantages and might be too complex to be carried out. Authors suggest instead a three-group long-term trial design, which could provide comparison between test drug and active comparator along with comparison between the test drug and placebo. This alternative could arguably be much easier to carry out compared with the hybrid design. Conclusions: The three-group long-term design merits further discussion and evaluation.

Medication reconciliation at patient admission: a randomized controlled trial

Objective: To measure length of hospital stay (LHS) in patients receiving medication reconciliation. Secondary characteristics included analysis of number of preadmission medications, medications prescribed at admission, number of discrepancies, and pharmacists interventions done and accepted by the attending physician. Methods: A 6 month, randomized, controlled trial conducted at a public teaching hospital in southern Brazil. Patients admitted to general wards were randomized to receive usual care or medication reconciliation, performed within the first 72 hours of hospital admission. Results: The randomization process assigned 68 patients to UC and 65 to MR. LHS was 10±15 days in usual care and 9±16 days in medication reconciliation (p=0.620). The total number of discrepancies was 327 in the medication reconciliation group, comprising 52.6% of unintentional discrepancies. Physicians accepted approximately 75.0% of the interventions. Conclusion: These results highlight weakness at patient transition care levels in a public teaching hospital. LHS, the primary outcome, should be further investigated in larger studies. Medication reconciliation was well accepted by physicians and it is a useful tool to find and correct discrepancies, minimizing the risk of adverse drug events and improving patient safety.

Increased hospital-based physical rehabilitation and information provision after intensive care unit discharge: the RECOVER randomized clinical trial.

Importance: critical illness results in disability and reduced health-related quality of life (HRQOL), but the optimum timing and components of rehabilitation are uncertain. Objective: to evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post–intensive care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility, HRQOL, and prevalent disabilities. Design, Setting, and Participants: a parallel group, randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from the ICU between December 1, 2010, and January 31, 2013, who required at least 48 hours of mechanical ventilation. Analysis for the primary outcome and other 3-month outcomes was performed between June and August 2013; for the 6- and 12-month outcomes and the health economic evaluation, between March and April 2014. Interventions: during the post-ICU hospital stay, both groups received physiotherapy and dietetic, occupational, and speech/language therapy, but patients in the intervention group received rehabilitation that typically increased the frequency of mobility and exercise therapies 2- to 3-fold, increased dietetic assessment and treatment, used individualized goal setting, and provided greater illness-specific information. Intervention group therapy was coordinated and delivered by a dedicated rehabilitation practitioner. Main Outcomes and Measures: the Rivermead Mobility Index (RMI) (range 0-15) at 3 months; higher scores indicate greater mobility. Secondary outcomes included HRQOL, psychological outcomes, self-reported symptoms, patient experience, and cost-effectiveness during a 12-month follow-up (completed in February 2014). Results: median RMI at randomization was 3 (interquartile range [IQR], 1-6) and at 3 months was 13 (IQR, 10-14) for the intervention and usual care groups (mean difference, −0.2 [95% CI, −1.3 to 0.9; P = .71]). The HRQOL scores were unchanged by the intervention (mean difference in the Physical Component Summary score, −0.1 [95% CI, −3.3 to 3.1; P = .96]; and in the Mental Component Summary score, 0.2 [95% CI, −3.4 to 3.8; P = .91]). No differences were found for self-reported symptoms of fatigue, pain, appetite, joint stiffness, or breathlessness. Levels of anxiety, depression, and posttraumatic stress were similar, as were hand grip strength and the timed Up & Go test. No differences were found at the 6- or 12-month follow-up for any outcome measures. However, patients in the intervention group reported greater satisfaction with physiotherapy, nutritional support, coordination of care, and information provision. Conclusions and Relevance: post-ICU hospital-based rehabilitation, including increased physical and nutritional therapy plus information provision, did not improve physical recovery or HRQOL, but improved patient satisfaction with many aspects of recovery.

Granulocyte-colony-stimulating factor mobilizes bone marrow stem cells in patients with subacute ischemic stroke: the Stem Cell Trial of Recovery EnhanceMent After Stroke (STEMS) Pilot Randomized, Controlled Trial (ISRCTN 16784092)

Background and Purpose - Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34 stem cells. Methods - We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 g/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34 stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment. Results - Thirty-six patients, whose mean SD age was 768 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 g/kg) increased CD34 count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P0.005). A dose-dependent rise in white cell count (P0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days. Conclusions - ”G-CSF is effective at mobilizing bone marrow CD34 stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined. (Stroke. 2006;37:2979-2983.)

Efficacy of early skin-to-skin contact on the rate of exclusive breastfeeding in term neonates: a randomized controlled trial

Background: Despite multiple benefits of breast milk, the rates of exclusive breastfeeding in developing countries are low. Objective: To evaluate the efficacy of early skin -to -skin contact (SSC) on the rate of exclusive breastfeeding (EBF) at 6 weeks of age among term neonates born by vaginal delivery. Methods: Term neonates born by vaginal delivery and did not require any resuscitation were randomized at birth to SSC (n=100) and control (n=100) group. Immediately after clamping the umbilical cord, SSC group neonates were placed on the bare bosom of mother and control group neonates were placed under a radiant warmer for a period of 45 minutes each while mothers underwent management of the third stage of labor and episiotomy repair. Pain experienced by mother during episiotomy repair was recorded using a numerical pain scale The primary outcome evaluated was the rate of exclusive breastfeeding at 6 weeks of postnatal age. Results: A significantly higher proportion of neonates were exclusively breastfeed at 6 weeks of age in the SSC group than in the control group (72% vs. 57.6%, p=0.04, relative risk: 1.3, 95% confidence interval: 1.0 -1.6). The pain score during episiotomy repair in mothers of the SSC group was significantly lower than the control group (4.74±0.85 versus 5.34±0.81; P <0.01). Conclusions: Early SSC significantly improved the rate of exclusively breastfeeding at 6 weeks of age among healthy term neonates. An important additional effect was a decrease in the amount of pain that mothers in the SSC group experienced during episiotomy repair.

Open-label placebo treatment in chronic low back pain: A randomized controlled trial

This randomized controlled trial was performed to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. Pain severity was assessed on three 0- to 10-point Numeric Rating Scales, scoring maximum pain, minimum pain, and usual pain, and a composite, primary outcome, total pain score. Our other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. We randomized 97 adults reporting persistent low back pain for more than 3 months' duration and diagnosed by a board-certified pain specialist. Eighty-three adults completed the trial. Compared to TAU, OLP elicited greater pain reduction on each of the three 0- to 10-point Numeric Rating Scales and on the 0- to 10-point composite pain scale (P < 0.001), with moderate to large effect sizes. Pain reduction on the composite Numeric Rating Scales was 1.5 (95% confidence interval: 1.0-2.0) in the OLP group and 0.2 (-0.3 to 0.8) in the TAU group. Open-label placebo treatment also reduced disability compared to TAU (P < 0.001), with a large effect size. Improvement in disability scores was 2.9 (1.7-4.0) in the OLP group and 0.0 (-1.1 to 1.2) in the TAU group. After being switched to OLP, the TAU group showed significant reductions in both pain (1.5, 0.8-2.3) and disability (3.4, 2.2-4.5). Our findings suggest that OLP pills presented in a positive context may be helpful in chronic low back pain.

Application of Lidocaine Spray for Tracheal Intubation in Neonates - A Clinical Trial Study

Background: Tracheal intubation is extremely distressing, painful, and may influence heart rate and blood pressure. Sedatives, analgesics, and muscle relaxants are not commonly used for intubation in neonates. Objectives: This study aimed to evaluate the effects of lidocaine spray as a non-intravenous drug before neonatal intubation on blood pressure, heart rate, oxygen saturation and time of intubation. Patients and Methods: In a randomized, controlled study each neonate was randomly assigned to one of the two study groups by staffs who were not involved in the infant's care. The allocation concealment was kept in an opaque sealed envelope, and the investigators, the patient care team, and the assessors were blinded to the treatment allocation. The selected setting was NICU unit of a teaching hospital in Ilam city, Iran and participants were 60 neonates with indication of tracheal intubation with gestational age >30 weeks. Patients in the treatment group received lidocaine spray and the placebo group received spray of normal saline prior to intubation. Main outcome measurements were the mean rates of blood pressure, heart rate, oxygen saturation, intubation time and lidocaine side effects were measured before and after intubation. Results: Totally 60 newborns including 31 boys and 29 girls were entered into the study (drug group n = 30; placebo group n = 30). Boy/girl ratio in treatment and placebo groups were 1.3 and 0.88, respectively. Mean age ± SD of participants was 34.1 ± 24.8 hours (treatment: 35.3 ± 25.7; placebo: 32.9 ± 24.3; P < 0.0001). Mean weight ± SD of neonates was 2012.5 ± 969 g. Application of lidocaine spray caused a significant reduction of mean intubation time among treatment group compared with placebo group (treatment: 15.03 ± 2.2 seconds; placebo: 18.3 ± 2.3 seconds; P < 0.0001). Mean blood pressure, heart rate and oxygen saturation rate, among neonates in treatment group was reduced after intubation compared with their relevant figures before intubation; however, their differences were not statistically significant except for mean oxygen saturation rate that was reduced significantly in placebo group. No side effects were observed during study. Conclusions: Though the current study revealed some promising results in the application of lidocaine spray during neonatal intubation without any considerable side effects; however, the current investigation could only be considered as a pilot study for further attempts in different locations with higher sample sizes and in different situations.

Chromium supplementation in patients with type 2 diabetes and high risk of type 2 diabetes: a meta-analysis of randomized controlled trials

Introduction: Chromium is an essential trace mineral for carbohydrate and lipid metabolism, which is currently prescribed to control diabetes mellitus. Results of previous systematic reviews and meta-analyses of chromium supplementation and metabolic profiles in diabetes have been inconsistent. Aim: The objective of this meta-analysis was to assess the effects on metabolic profiles and safety of chromium supplementation in type 2 diabetes mellitus and cholesterol. Methods: Literature searches in PubMed, Scopus and Web of Science were made by use of related terms-keywords and randomized clinical trials during the period of 2000-2014. Results: Thirteen trials fulfilled the inclusion criteria and were included in this systematic review. Total doses of Cr supplementation and brewer's yeast ranged from 42 to 1,000 µg/day, and duration of supplementation ranged from 30 to 120 days. The analysis indicated that there was a significant effect of chromium supplementation in diabetics on fasting plasma glucose with a weighted average effect size of -29.26 mg/dL, p = 0.01, CI 95% = -52.4 to -6.09; and on total cholesterol with a weighted average effect size of -6.7 mg/dL, p = 0.01, CI 95% = -11.88 to -1.53. Conclusions: The available evidence suggests favourable effects of chromium supplementation on glycaemic control in patients with diabetes. Chromium supplementation may additionally improve total cholesterol levels.

Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran

Background: Helicobacter Pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H.pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics. Objectives: In this study we aimed to assess the effect of S. boulardii supplementation on H.pylori eradication among children in our region. Patients and Methods: In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H.pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces Boulardii and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05. Results: 24 children completed the study. The mean HpSA reduced from 0.40 ± 0.32 to 0.21 ± 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 ± 0.19 decrease in the study group whereas the same value was 0.0048 ± 0.12 for the controls, again stating a significant difference (P = 0.01). Conclusions: Saccharomyces boulardii has a positive effect on reducing the colonization of H.pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy.