Effect of Vitamin D Supplementation on Cardiometabolic Risks and Health-Related Quality of Life among Urban Premenopausal Women in a Tropical Country – A Randomized Controlled Trial

Background

Many observational studies linked vitamin D to cardiometabolic risks besides its pivotal role in musculoskeletal diseases, but evidence from trials is lacking and inconsistent.

Aim

To determine whether Vitamin D supplementation in urban premenopausal women with vitamin D deficiency can improve cardiometabolic risks and health-related quality of life (HRQOL).

Design

A double-blind randomized controlled trial was conducted in Kuala Lumpur, Malaysia. A total of 192 vitamin D deficient (<50 nmol/l) premenopausal women were randomized to receive either vitamin D 50,000 IU or placebo once a week for 2 months and then monthly for 10 months. Primary outcomes were serum 25(OH)D, serum lipid profiles, blood pressure and HOMA-IR measured at baseline, 6 months and 12 months. HRQOL was assessed with SF-36 at baseline and 12 months.

Results

Ninety three and ninety-nine women were randomised into intervention and placebo groups respectively. After 12 months, there were significant differences in the serum 25(OH)D concentration (mean difference: 49.54; 95% CI: 43.94 to 55.14) nmol/l) and PTH levels (mean difference: −1.02; 95% CI: −1.67 to −0.38 pmol/l) in the intervention group compared to placebo group. There was significant difference between treatment group in both serum 25(OH)D and PTH. There was no effect of supplementation on HOMA-IR, serum lipid profiles and blood pressure (all p>0.05) between two groups. There was a small but significant improvement in HRQOL in the components of vitality (mean difference: 5.041; 95% CI: 0.709 to 9.374) and mental component score (mean difference: 2.951; 95% CI: 0.573 to 5.329) in the intervention group compared to placebo group.

Conclusion

Large and less frequent dosage vitamin D supplementation was safe and effective in the achievement of vitamin D sufficiency. However, there was no improvement in measured cardiometabolic risk factors in premenopausal women. Conversely vitamin D supplementation improves some components of HRQOL.

Trial Registration

Australian New Zealand Clinical Trial Registry ACTRN12612000452897     

Vitamin D? Supplementation in Batswana Children and Adults with HIV: A Pilot Double Blind Randomized Controlled Trial

ObjectivesSince vitamin D insufficiency is common worldwide in people with HIV, we explored safety and efficacy of high dose cholecalciferol (D₃) in Botswana, and evaluated potential modifiers of serum 25 hydroxy vitamin D change (Δ25D).DesignProspective randomized double-blind 12-week pilot trial of subjects ages 5.0–50.9 years.MethodsSixty subjects randomized within five age groups to either 4000 or 7000IU per day of D₃ and evaluated for vitamin D, parathyroid hormone, HIV, safety and growth status. Efficacy was defined as serum 25 hydroxy vitamin D (25D) ≥32ng/mL, and safety as no simultaneous elevation of serum calcium and 25D. Also assessed were HIV plasma viral RNA viral load (VL), CD4%, anti-retroviral therapy (ART) regime, and height-adjusted (HAZ), weight-adjusted (WAZ) and Body Mass Index (BMIZ) Z scores.ResultsSubjects were 50% male, age (mean±SD) 19.5±11.8 years, CD4% 31.8±10.4, with baseline VL log₁₀ range of <1.4 to 3.8 and VL detectable (>1.4) in 22%. From baseline to 12 weeks, 25D increased from 36±9ng/ml to 56±18ng/ml (p<0.0001) and 68% and 90% had 25D ≥32ng/ml, respectively (p = 0.02). Δ25D was similar by dose. No subjects had simultaneously increased serum calcium and 25D. WAZ and BMIZ improved by 12 weeks (p<0.04). HAZ and CD4% increased and VL decreased in the 7000IU/d group (p<0.04). Younger (5–13y) and older (30–50y) subjects had greater Δ25D than those 14–29y (26±17 and 28±12 vs. 11±11ng/ml, respectively, p≤0.001). Δ25D was higher with efavirenz or nevirapine compared to protease inhibitor based treatment (22±12, 27±17, vs. 13±10, respectively, p≤0.03).ConclusionsIn a pilot study in Botswana, 12-week high dose D₃ supplementation was safe and improved vitamin D, growth and HIV status; age and ART regimen were significant effect modifiers.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02189902","term_id":"NCT02189902"}}NCT02189902     

Cognitive Function in Adult Offspring of Women with Gestational Diabetes–The Role of Glucose and Other Factors

Objective

We aimed to evaluate cognitive function in adult offspring of women with diet-treated gestational diabetes and to study potential associations with maternal glucose values.

Materials and Methods

In 2003–2005 cognitive function was assessed in a cohort of 18–27 year old offspring of women with diet-treated gestational diabetes mellitus (n = 153) and offspring from the background population (n = 118). The main outcome measure was global cognitive score derived from Raven’s Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. Maternal fasting- and 2-hour blood glucose values from the diagnostic oral glucose tolerance test were used as exposure variables.

Results

Offspring of women with gestational diabetes mellitus had a lower global cognitive score, than offspring from the background population (93.1 vs. 100.0, P<0.001). However, when adjusted for maternal age at delivery, parity, smoking during pregnancy, pre-pregnancy overweight, family social class, parental educational level, gender, birth weight, gestational age, perinatal complications and offspring age at follow-up, the difference was no longer statistically significant. Offspring global cognitive score decreased significantly with increasing maternal fasting glucose (β = −4.5, 95% CI −8.0 to −0.9, P = 0.01) and 2-hour glucose (β = −1.5, −2.9 to −0.2, P = 0.03) in univariate general linear models, but not when adjusted for family social class and parental educational level.

Conclusions

Lower cognitive test scores in adult offspring of women with diet-treated gestational diabetes were explained by well known predictors of cognitive function, but not by maternal hyperglycaemia during pregnancy. We find it reassuring that mild intrauterine hyperglycaemia does not seem to have adverse effect on offspring cognitive function.     

Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion,Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized,Placebo-Controlled Trial

Objectives

To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers.

Design

6-month randomized, placebo-controlled trial.

Participants

Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45).

Intervention

Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months.

Measurements

Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin.

Results

Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed.

Conclusions

Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12609000043235     

No Impact of Vitamin D on the CYP3A Biomarker 4β-Hydroxycholesterol in Patients with Abnormal Glucose Regulation

Purpose

To investigate the effect of vitamin D3 on hepatic Cytochrome P450 enzyme (CYP) 3A4 in patients with abnormal glucose regulation using the endogenous marker 4β-hydroxycholesterol (4β-OHC):cholesterol ratio.

Methods

The present study took advantage of a trial primarily aiming to investigate the effect of vitamin D3 on beta cell function and insulin sensitivity in patients with abnormal glucose regulation. 44 subjects were randomized to receive vitamin D3, 30000 IU given orally once weekly or placebo for 8 weeks. The two sample t-test was used to test the means of the intra-individual differences of 4β-OHC:cholesterol ratio between the two groups.

Results

Mean (SD) 4β-OHC in the whole group of patients before and after the intervention was 26 (11) ng/ml and 26 (12). Mean (SD) 4β-OHC:cholesterol ratio in the whole group of patients before and after the intervention was 0.12 (0.046) and 0.13 (0.047). In the Vitamin D group mean (SD) serum 25-OH-vitamin D3 increased from 46 (16) to 85nM (13) during the corresponding time period. To investigate the impact of vitamin D3 on hepatic CYP3A4 we calculated the mean intra-individual differences in 4β-OHC:cholesterol ratio (delta 4β-OHC:cholesterol ratio) before versus after the intervention in the two treatment groups. The difference (95% CI) between delta 4β-OHC:cholesterol ratio in the control group and intervention group was -0.0010 (-0.0093, 0.0072), a difference being not statistically significant (p = 0.80).

Conclusions

We provide further evidence that vitamin D3 may not substantially affect hepatic CYP3A4. This does not exclude the possibility of an impact of intestinal first-pass metabolism of orally administered drugs which should be investigated.

Trial Registration

ClinicalTrials.gov NCT01497132     

Effects of Dexamethasone and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation – A Randomized Controlled Trial

Objectives

This study investigated the effects of dexamethasone and insulin, when administered at 3^rd or 10^th day of lactation on energy and protein metabolism in dairy cows.

Materials and Methods

Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow.

Results

There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum) on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and protein percentages.

Conclusions

The results suggested that administration of glucocorticoids in early lactation resulted in short-term improvement of metabolism in postpartum dairy cows in biochemical terms.     

Does Magnesium Supplementation Improve Body Composition and Muscle Strength in Middle-Aged Overweight Women? A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Muscle strength, an independent predictor of metabolic disorders, disability, and mortality, reduces gradually with advancing age. Little is known about the influence of nutritional intervention on muscle strength in middle-aged. The aim of the present study is to examine whether magnesium could improve body composition and muscle strength in middle-aged overweight women. In this double-blinded, placebo-controlled, randomized trial, a total of 74 healthy middle-aged overweight women (25?≤?BMI?≤?30 kg/m²) received either 250 mg magnesium in the form of magnesium oxide or placebo daily for 8 weeks. Body composition was assessed using Bioelectrical Impedance Analysis (BIA). Handgrip strength and knee extension strength were measured with isometric dynamometry. Functional mobility was assessed using Time Get Up and Go Test (TGUG). A significant increase in mean lean body mass was observed (P?=?0.05) accompanied with a significant decrease in fat mass (P?=?0.02) solely in the magnesium group at the end of 8 weeks compared to baseline values but the changes did not reach significant as compared to placebo group. Handgrip strength and TGUG improved in the magnesium group compared to baseline but they were not significant compared to placebo. There were no significant differences in increasing knee extension strength in the magnesium group as compared with placebo. Baseline values of serum magnesium and muscle strength of participants did not indicate any influences on response to magnesium supplementation. Our findings indicate that magnesium as magnesium oxide, 250 mg/day, for 8 weeks do not lead to a significant greater gain in muscle strength and function compared to placebo.     

Transection Speed and Impact on Perioperative Inflammatory Response – A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection

Background

Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear.

Materials and Methods

This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm²/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality.

Results

Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm²/min vs. Stapler: 10.8 (6.1) cm²/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020).

Conclusions

Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time.

Trial Registration

ClinicalTrials.gov NCT01785212     

Impact of Osteopathic Treatment on Pain in Adult Patients with Cystic Fibrosis – A Pilot Randomized Controlled Study

Background

Pain is a common complication in patients with cystic fibrosis (CF) and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT) on pain in adults with CF.

Methods

A pilot multicenter randomized controlled trial was conducted with three parallel arms: OMT (group A, 16 patients), sham OMT (sham treatment, group B, 8 patients) and no treatment (group C, 8 patients). Medical investigators and patients were double-blind to treatment for groups A and B, who received OMT or sham OMT monthly for 6 months. Pain was rated as a composite of its intensity and duration over the previous month. The evolution of chest/back pain after 6 months was compared between group A and groups B+C combined (control group). The evolution of cervical pain, headache and quality of life (QOL) were similarly evaluated.

Results

There was no statistically significant difference between the treatment and control groups in the decrease of chest/back pain (difference = −2.20 IC95% [−4.81; 0.42], p = 0.098); also, group A did not differ from group B. However, chest/back pain decreased more in groups A (p = 0.002) and B (p = 0.006) than in group C. Cervical pain, headache and QOL scores did not differ between the treatment and control groups.

Conclusion

This pilot study demonstrated the feasibility of evaluating the efficacy of OMT to treat the pain of patients with CF. The lack of difference between the group treated with OMT and the control group may be due to the small number of patients included in this trial, which also precludes any definitive conclusion about the greater decrease of pain in patients receiving OMT or sham OMT than in those with no intervention.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01293019","term_id":"NCT01293019"}}NCT01293019     

Interactive Cognitive-Motor Step Training Improves Cognitive Risk Factors of Falling in Older Adults – A Randomized Controlled Trial

Purpose

Interactive cognitive-motor training (ICMT) requires individuals to perform both gross motor movements and complex information processing. This study investigated the effectiveness of ICMT on cognitive functions associated with falls in older adults.

Methods

A single-blinded randomized controlled trial was conducted in community-dwelling older adults (N = 90, mean age 81.5±7) without major cognitive impairment. Participants in the intervention group (IG) played four stepping games that required them to divide attention, inhibit irrelevant stimuli, switch between tasks, rotate objects and make rapid decisions. The recommended minimum dose was three 20-minute sessions per week over a period of 16 weeks unsupervised at home. Participants in the control group (CG) received an evidence-based brochure on fall prevention. Measures of processing speed, attention/executive function (EF), visuo-spatial ability, concerns about falling and depression were assessed before and after the intervention.

Results

Eighty-one participants (90%) attended re-assessment. There were no improvements with respect to the Stroop Stepping Test (primary outcome) in the intervention group. Compared to the CG, the IG improved significantly in measures of processing speed, visuo-spatial ability and concern about falling. Significant interactions were observed for measures of EF and divided attention, indicating group differences varied for different levels of the covariate with larger improvements in IG participants with poorer baseline performance. The interaction for depression showed no change for the IG but an increase in the CG for those with low depressive symptoms at baseline. Additionally, low and high-adherer groups differed in their baseline performance and responded differently to the intervention. Compared to high adherers, low adherers improved more in processing speed and visual scanning while high-adherers improved more in tasks related to EF.

Conclusions

This study shows that unsupervised stepping ICMT led to improvements in specific cognitive functions associated with falls in older people. Low adherers improved in less complex functions while high-adherers improved in EF.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12613000671763     

Impact of Three Oral Antidiabetic Drugs on Markers of β-Cell Function in Patients with Type 2 Diabetes: A Meta-Analysis

Background

The effect of metformin, pioglitazone and sitagliptin on β-cell function in the treatment of type 2 diabetes is controversial. Therefore, we performed a systematic review and meta-analysis to obtain a better understanding in the β-cell effects of metformin, pioglitazone and sitagliptin.

Methods

We searched Pubmed and the Cochrane Center Register of Controlled Trials to identify relevant studies. Trials investigating effects of sitagliptin, metformin or pioglitazone on β-cell function were identified. The primary outcomes were homeostasis model assessment of β-cells (HOMA-β) and proinsulin/insulin ratio (PI/IR). Secondary outcome was hemoglobin A1c level. We used version 2 of the Comprehensive Meta Analysis software for all statistical analyses.

Results

Metformin monotherapy was more effective than sitagliptin in improving HOMA-β (18.01% (95% CI 11.09% to 24.94%) vs. 11.29% (95% CI 9.21% to 13.37%), P = 0.040) and more effective (−0.137 (95% CI −0.082 to −0.192)) than both sitagliptin (−0.064 (95% CI −0.036 to −0.092), P = 0.019) and pioglitazone (−0.068 (95% CI −0.044 to −0.093), P = 0.015) in decreasing PI/IR. Metformin and sitagliptin combined (40.23% (95%CI 32.30% to 48.16%)) were more effective than sitagliptin and pioglitazone (11.82% (95% CI 6.61% to 17.04%), P = 0.000) and pioglitazone and metformin(9.81% (95% CI 1.67% to 17.95%), P = 0.022) in improving HOMA-β and decreasing PI/IR (−0.177 (95% CI −0.118 to −0.237); −0.080 (95% CI −0.045 to −0.114), P = 0.007; −0.038 (95% CI, −0.005 to 0.071), P = 0.023).

Limitations

The included RCTs were of short duration (12–54 weeks). We could not determine long term effects on β-cells.

Conclusions

Metformin improves β-cell function more effectively than pioglitazone or sitagliptin in type 2 diabetes patients. Metformin and sitagliptin improved HOMA-β and PI/IR more than other combinations.     

Immunogenicity,Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial

Background

The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown.

Methods

600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination.

Results

Following one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups.

Conclusions

Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01028326","term_id":"NCT01028326"}}NCT01028326     

SAVVY? (C31G) Gel for Prevention of HIV infection in Women: A Phase 3, Double-Blind,Randomized, Placebo-Controlled Trial in Ghana

Objective

The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.

Methodology/Principal Findings

This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between March 2004 and February 2006 in Accra and Kumasi, Ghana. We enrolled 2142 HIV-negative women at high risk of HIV infection, and randomized them to SAVVY or placebo gel. Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transudate specimens and adverse events. We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group. No clinically significant differences in the overall frequency of adverse events, abnormal pelvic examination findings, or abnormal laboratory results were seen between treatment groups. However, more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group (13.0% versus 9.4%). Seventeen HIV seroconversions occurred; eight in participants randomized to SAVVY and nine in participants receiving placebo. The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group (p = 0.731), with a hazard ratio (SAVVY versus placebo) of 0.88 (95% confidence interval 0.33, 2.27). Because of a lower-than-expected HIV incidence, we were unable to achieve the required number of HIV infections (66) to obtain the desired study power.

Conclusions/Significance

SAVVY was not associated with increased adverse events overall, but was associated with higher reporting of reproductive adverse events. Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00129532","term_id":"NCT00129532"}}NCT00129532     

Effectiveness of Home-Based Cupping Massage Compared to Progressive Muscle Relaxation in Patients with Chronic Neck Pain—A Randomized Controlled Trial

Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity (0–100 mm visual analog scale; VAS) after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female) were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31). After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01500330","term_id":"NCT01500330"}}NCT01500330     

Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

BackgroundBreast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.MethodsBetween April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective).ResultsFour hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005).ConclusionsWithholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity.

Trial Registration

ClinicalTrials.gov NCT01199874     

Impact of a Participatory Intervention with Women’s Groups on Psychological Distress among Mothers in Rural Bangladesh: Secondary Analysis of a Cluster-Randomised Controlled Trial

Background

Perinatal common mental disorders (PCMDs) are a major cause of disability among women and disproportionately affect lower income countries. Interventions to address PCMDs are urgently needed in these settings, and group-based and peer-led approaches are potential strategies to increase access to mental health interventions. Participatory women’s health groups led by local women previously reduced postpartum psychological distress in eastern India. We assessed the effect of a similar intervention on postpartum psychological distress in rural Bangladesh.

Method

We conducted a secondary analysis of data from a cluster-randomised controlled trial with 18 clusters and an estimated population of 532,996. Nine clusters received an intervention comprising monthly meetings during which women’s groups worked through a participatory learning and action cycle to develop strategies for improving women’s and children’s health. There was one group for every 309 individuals in the population, 810 groups in total. Mothers in nine control clusters had access to usual perinatal care. Postpartum psychological distress was measured with the 20-item Self Reporting Questionnaire (SRQ-20) between six and 52 weeks after delivery, during the months of January to April, in 2010 and 2011.

Results

We analysed outcomes for 6275 mothers. Although the cluster mean SRQ-20 score was lower in the intervention arm (mean 5.2, standard deviation 1.8) compared to control (5.3, 1.2), the difference was not significant (β 1.44, 95% CI 0.28, 3.08).

Conclusions

Despite promising results in India, participatory women’s groups focused on women’s and children’s health had no significant effect on postpartum psychological distress in rural Bangladesh.