Morbidity and mortality in breastfed and formula-fed infants of HIV-1-infected women: A randomized clinical trial.

CONTEXT: Breastfeeding among women infected with human immunodeficiency virus type 1 (HIV-1) is associated with substantial risk of HIV-1 transmission, but little is known about the morbidity risks associated with formula feeding in infants of HIV-1-infected women in resource-poor settings. OBJECTIVE: To compare morbidity, nutritional status, mortality adjusted for HIV-1 status, and cause of death among formula-fed and breastfed infants of HIV-1-infected women. DESIGN: Randomized clinical trial conducted between 1992 and 1998. SETTING: Four antenatal clinics in Nairobi, Kenya. PARTICIPANTS: Of 401 live-born, singleton, or first-born twin infants of randomized HIV-1-seropositive mothers, 371 were included in the analysis of morbidity and mortality. INTERVENTIONS: Mothers were randomly assigned either to use formula (n = 186) or to breastfeed (n = 185) their infants. MAIN OUTCOME MEASURES: Mortality rates, adjusted for HIV-1 infection status; morbidity; and nutritional status during the first 2 years of life. RESULTS: Two-year estimated mortality rates among infants were similar in the formula-feeding and breastfeeding arms (20.0% vs 24.4%; hazard ratio [HR], 0.8; 95% confidence interval [CI], 0.5-1.3), even after adjusting for HIV-1 infection status (HR, 1.1; 95% CI, 0.7-1.7). Infection with HIV-1 was associated with a 9.0-fold increased mortality risk (95% CI, 5.3-15.3). The incidence of diarrhea during the 2 years of follow-up was similar in formula and breastfeeding arms (155 vs 149 per 100 person-years, respectively). The incidence of pneumonia was identical in the 2 groups (62 per 100 person-years), and there were no significant differences in incidence of other recorded illnesses. Infants in the breastfeeding arm tended to have better nutritional status, significantly so during the first 6 months of life. CONCLUSIONS: In this randomized clinical trial, infants assigned to be formula fed or breastfed had similar mortality rates and incidence of diarrhea and pneumonia during the first 2 years of life. However, HIV-1-free survival at 2 years was significantly higher in the formula arm. With appropriate education and access to clean water, formula feeding can be a safe alternative to breastfeeding for infants of HIV-1-infected mothers in a resource-poor setting.     

Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study

Context  Postnatal transmission of human immunodeficiency virus-1 (HIV) via breastfeeding reverses gains achieved by perinatal antiretroviral interventions. Objective  To compare the efficacy and safety of 2 infant feeding strategies for the prevention of postnatal mother-to-child HIV transmission. Design, Setting, and Patients  A 2 x 2 factorial randomized clinical trial with peripartum (single-dose nevirapine vs placebo) and postpartum infant feeding (formula vs breastfeeding with infant zidovudine prophylaxis) interventions. In Botswana between March 27, 2001, and October 29, 2003, 1200 HIV-positive pregnant women were randomized from 4 district hospitals. Infants were evaluated at birth, monthly until age 7 months, at age 9 months, then every third month through age 18 months. Intervention  All of the mothers received zidovudine 300 mg orally twice daily from 34 weeks' gestation and during labor. Mothers and infants were randomized to receive single-dose nevirapine or placebo. Infants were randomized to 6 months of breastfeeding plus prophylactic infant zidovudine (breastfed plus zidovudine), or formula feeding plus 1 month of infant zidovudine (formula fed). Main Outcome Measures  Primary efficacy (HIV infection by age 7 months and HIV-free survival by age 18 months) and safety (occurrence of infant adverse events by 7 months of age) end points were evaluated in 1179 infants. Results  The 7-month HIV infection rates were 5.6% (32 infants in the formula-fed group) vs 9.0% (51 infants in the breastfed plus zidovudine group) (P = .04; 95% confidence interval for difference, –6.4% to –0.4%). Cumulative mortality or HIV infection rates at 18 months were 80 infants (13.9%, formula fed) vs 86 infants (15.1% breastfed plus zidovudine) (P = .60; 95% confidence interval for difference, –5.3% to 2.9%). Cumulative infant mortality at 7 months was significantly higher for the formula-fed group than for the breastfed plus zidovudine group (9.3% vs 4.9%; P = .003), but this difference diminished beyond month 7 such that the time-to-mortality distributions through age 18 months were not significantly different (P = .21). Conclusions  Breastfeeding with zidovudine prophylaxis was not as effective as formula feeding in preventing postnatal HIV transmission, but was associated with a lower mortality rate at 7 months. Both strategies had comparable HIV-free survival at 18 months. These results demonstrate the risk of formula feeding to infants in sub-Saharan Africa, and the need for studies of alternative strategies. Trial Registration  clinicaltrials.gov Identifier: NCT00197587      

腹及腹腔镜手术对腹膜纤溶系统影响的临床研究

目的探讨腹腔镜与开腹手术中腹膜纤维蛋白溶酶的变化。方法在腹腔镜与开腹手术前、后、立即，分别测量腹膜组织中组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物(PAI-1)的浓度及t-PA的活性。结果腹膜组织t PA浓度在腹腔镜手术和传统腹部手术两组术中均下降，在传统腹部手术组下降更显著(P<0.05)，而腹膜组织PAI-1水平在腹腔镜手术组术前较高（P<0.05），在传统腹部手术组术中明显升高。手术后，两组PAI-1浓度无显著差异。t-PA活性在两组术前、后均无明显差异，但术中两组均显著下降(P<0.05) 。结论腹腔镜和传统腹部手术对腹膜的影响是相似的，腹腔镜手术最初腹膜组织中PAI-1浓度的升高是由于CO₂气腹造成的，并影响腹膜组织的修复。     

Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial

Context  Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen. Objective  To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection. Design  The AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and enrolling treatment-naive, HIV-1–infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG. Interventions  Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen). Main Outcome Measures  Time to virologic failure (defined as time to first of 2 successive HIV-1 RNA levels 200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes. Results  Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log₁₀ (72 444) copies/mL and CD4 cell count of 240 cells/mm³ were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69-1.33; P = .73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95% confidence interval, 1.18-2.34; P = .003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively (P = .59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P = .39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different. Conclusions  In treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit. Clinical Trials Registration  clinicaltrials.gov Identifier: NCT00013520      

Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial

Background:Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients.Methods:A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg⁻¹·day⁻¹) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o’clock, 11 to 13 o’clock, and 17 to 19 o’clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups.Results:There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3–10.3] vs. 10.7 [9.1–12.1] mmol/L, Z = −2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1–63.7]% vs. 11.8 [3.0–36.7]%, Z = −2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050).Conclusions:In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients.Trial RegistrationClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT03439618","term_id":"NCT03439618"}}NCT03439618; https://clinicaltrials.gov/ct2/show/record/{"type":"clinical-trial","attrs":{"text":"NCT03439618","term_id":"NCT03439618"}}NCT03439618     

Dictated versus database-generated discharge summaries: a randomized clinical trial

BACKGROUND: Hospital discharge summaries communicate information necessary for continuing patient care. They are most commonly generated by voice dictation and are often of poor quality. The objective of this study was to compare discharge summaries created by voice dictation with those generated from a clinical database. METHODS: A randomized clinical trial was performed in which discharge summaries for patients discharged from a general internal medicine service at a tertiary care teaching hospital in Ottawa were created by voice dictation (151 patients) or from a database (142 patients). Patients had been admitted between September 1996 and June 1997. The trial was preceded by a baseline cohort study in which all summaries were created by dictation. For the database group, information on forms completed by housestaff was entered into a database and collated into a discharge summary. For the dictation group, housestaff dictated narrative letters. The proportion of patients for whom a summary was generated within 4 weeks of discharge was recorded. Physicians receiving the summary rated its quality, completeness, organization and timeliness on a 100-mm visual analogue scale. Housestaff preference was also determined. RESULTS: Patients in the database group and the dictation group were similar. A summary was much more likely to be generated within 4 weeks of discharge for patients in the database group than for those in the dictation group (113 [79.6%] v. 86 [57.0%]; p < 0.001). Summary quality was similar (mean rating 72.7 [standard deviation (SD) 19.3] v. 74.9 [SD 16.6]), as were assessments of completeness (73.4 [SD 19.8] v. 78.2 [SD 14.9]), organization (77.4 [SD 16.3] v. 79.3 [SD 17.2]) and timeliness (70.3 [SD 21.9] v. 66.2 [SD 25.6]). Many information items of interest were more likely to be included in the database-generated summaries. The database system created summaries faster and was preferred by housestaff. Dictated summaries in the baseline and randomized studies were similar, which indicated that the control group was not substantially different from the baseline cohort. INTERPRETATION: The database system significantly increased the likelihood that a discharge summary was created. Housestaff preferred the database system for summary generation. Physicians thought that the quality of summaries generated by the 2 methods was similar. The use of computer databases to create hospital discharge summaries is promising and merits further study and refinement.     

Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial

Context  In uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known. Objective  To test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning. Design, Setting, and Patients  Multicenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded. Intervention  Patients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines. Main Outcome Measure  Ventilator-free days to day 28. Results  The trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, –0.2 days; 95% CI, –3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, –3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure–free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28. Conclusion  Prone positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.      

Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial

Lianne C. Krab, MSc; Arja de Goede-Bolder, MD; Femke K. Aarsen, MA; Saskia M. F. Pluijm, PhD; Marlies J. Bouman, MA; Jos N. van der Geest, PhD; Maarten Lequin, MD, PhD; Coriene E. Catsman, MD, PhD; Willem Frans M. Arts, MD, PhD; Steven A. Kushner, MD, PhD; Alcino J. Silva, PhD; Chris I. de Zeeuw, MD, PhD; Henriëtte A. Moll, MD, PhD; Ype Elgersma, PhD

JAMA. 2008;300(3):287-294.

Context  Neurofibromatosis type 1 (NF1) is among the most common genetic disorders that cause learning disabilities. Recently, it was shown that statin-mediated inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase restores the cognitive deficits in an NF1 mouse model.

Objective  To determine the effect of simvastatin on neuropsychological, neurophysiological, and neuroradiological outcome measures in children with NF1.

Design, Setting, and Participants  Sixty-two of 114 eligible children (54%) with NF1 participated in a randomized, double-blind, placebo-controlled trial conducted between January 20, 2006, and February 8, 2007, at an NF1 referral center at a Dutch university hospital.

Intervention  Simvastatin or placebo treatment once daily for 12 weeks.

Main Outcome Measures  Primary outcomes were scores on a Rey complex figure test (delayed recall), cancellation test (speed), prism adaptation, and the mean brain apparent diffusion coefficient based on magnetic resonance imaging. Secondary outcome measures were scores on the cancellation test (standard deviation), Stroop color word test, block design, object assembly, Rey complex figure test (copy), Beery developmental test of visual-motor integration, and judgment of line orientation. Scores were corrected for baseline performance, age, and sex.

Results  No significant differences were observed between the simvastatin and placebo groups on any primary outcome measure: Rey complex figure test (β = 0.10; 95% confidence interval [CI], –0.36 to 0.56); cancellation test (β = –0.19; 95% CI, –0.67 to 0.29); prism adaptation (odds ratio = 2.0; 95% CI, 0.55 to 7.37); and mean brain apparent diffusion coefficient (β = 0.06; 95% CI, –0.07 to 0.20). In the secondary outcome measures, we found a significant improvement in the simvastatin group in object assembly scores (β = 0.54; 95% CI, 0.08 to 1.01), which was specifically observed in children with poor baseline performance (β = 0.80; 95% CI, 0.29 to 1.30). Other secondary outcome measures revealed no significant effect of simvastatin treatment.

Conclusion  In this 12-week trial, simvastatin did not improve cognitive function in children with NF1.

Trial Registration  isrctn.org Identifier: ISRCTN14965707

     

Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial

Context  Sexually transmitted infections (STIs) are common in female sex workers (FSWs) and may enhance susceptibility to infection with human immunodeficiency virus type 1 (HIV-1). Objective  To examine regular antibiotic prophylaxis in FSWs as a strategy for reducing the incidence of bacterial STIs and HIV-1. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial conducted between 1998-2002 among FSWs in an urban slum area of Nairobi, Kenya. Of 890 FSWs screened, 466 who were seronegative for HIV-1 infection were enrolled and randomly assigned to receive azithromycin (n = 230) or placebo (n = 236). Groups were well matched at baseline for sexual risk taking and STI rates. Intervention  Monthly oral administration of 1 g of azithromycin or identical placebo, as directly observed therapy. All participants were provided with free condoms, risk-reduction counseling, and STI case management. Main Outcome Measures  The primary study end point was incidence of HIV-1 infection. Secondary end points were the incidence of STIs due to Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, and Haemophilus ducreyi, as well as bacterial vaginosis. Analysis of herpes simplex virus type 2 (HSV-2) infection was performed post hoc. Results  Seventy-three percent of participants (n = 341) were followed up for 2 or more years or until they reached an administrative trial end point. Incidence of HIV-1 did not differ between treatment and placebo groups (4% [19 cases per 473 person-years of follow-up] vs 3.2% [16 cases per 495 person-years of follow-up] rate ratio [RR], 1.2; 95% CI, 0.6-2.5). Incident HIV-1 infection was associated with preceding infection with N gonorrhoeae (rate ratio [RR], 4.9; 95% CI, 1.7-14.3) or C trachomatis (RR, 3.0; 95% CI, 1.1-8.9). There was a reduced incidence in the treatment group of infection with N gonorrhoeae (RR, 0.46; 95% CI, 0.31-0.68), C trachomatis (RR, 0.38; 95% CI, 0.26-0.57), and T vaginalis (RR, 0.56; 95% CI, 0.40-0.78). The seroprevalence of HSV-2 infection at enrollment was 72.7%, and HSV-2 infection at baseline was independently associated with HIV-1 acquisition (RR, 6.3; 95% CI, 1.5-27.1). Conclusions  Despite an association between bacterial STIs and acquisition of HIV-1 infection, the addition of monthly azithromycin prophylaxis to established HIV-1 risk reduction strategies substantially reduced the incidence of STIs but did not reduce the incidence of HIV-1. Prevalent HSV-2 infection may have been an important cofactor in acquisition of HIV-1.      

Effect of Zuogui pill and Yougui pill on osteoporosis: a randomized controlled trial

OBJECTIVE

To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Yin and Yang tonic formula (CYYTF), in the treatment of osteoporosis and the underlying mechanism.

Neurobehavioral effects of dental amalgam in children: a randomized clinical trial

Context  Dental (silver) amalgam is a widely used restorative material containing 50% elemental mercury that emits small amounts of mercury vapor. No randomized clinical trials have determined whether there are significant health risks associated with this low-level mercury exposure. Objective  To assess the safety of dental amalgam restorations in children. Design  A randomized clinical trial in which children requiring dental restorative treatment were randomized to either amalgam for posterior restorations or resin composite instead of amalgam. Enrollment commenced February 1997, with annual follow-up for 7 years concluding in July 2005. Setting and Participants  A total of 507 children in Lisbon, Portugal, aged 8 to 10 years with at least 1 carious lesion on a permanent tooth, no previous exposure to amalgam, urinary mercury level <10 µg/L, blood lead level <15 µg/dL, Comprehensive Test of Nonverbal Intelligence IQ 67, and with no interfering health conditions. Intervention  Routine, standard-of-care dental treatment, with one group receiving amalgam restorations for posterior lesions (n = 253) and the other group receiving resin composite restorations instead of amalgam (n = 254). Main Outcome Measures  Neurobehavioral assessments of memory, attention/concentration, and motor/visuomotor domains, as well as nerve conduction velocities. Results  During the 7-year trial period, children had a mean of 18.7 tooth surfaces (median, 16) restored in the amalgam group and 21.3 (median, 18) restored in the composite group. Baseline mean creatinine-adjusted urinary mercury levels were 1.8 µg/g in the amalgam group and 1.9 µg/g in the composite group, but during follow-up were 1.0 to 1.5 µg/g higher in the amalgam group than in the composite group (P<.001). There were no statistically significant differences in measures of memory, attention, visuomotor function, or nerve conduction velocities (average z scores were very similar, near zero) for the amalgam and composite groups over all 7 years of follow-up, with no statistically significant differences observed at any time point (P values from .29 to .91). Starting at 5 years after initial treatment, the need for additional restorative treatment was approximately 50% higher in the composite group. Conclusions  In this study, children who received dental restorative treatment with amalgam did not, on average, have statistically significant differences in neurobehavioral assessments or in nerve conduction velocity when compared with children who received resin composite materials without amalgam. These findings, combined with the trend of higher treatment need later among those receiving composite, suggest that amalgam should remain a viable dental restorative option for children. Trial Registration  clinicaltrials.gov Identifier: NCT00066118      

Effect of Chinese herbs on immunoglobulin A nephropathy:a randomized controlled trial

OBJECTIVE: The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we applied randomly controlled trial to check the curative effect of Chinese herbs on patients with immunoglobulin A nephropathy (IgAN). METHODS: Twenty-six patients were randomly divided into group A (control group) treated with Western Medicine and group B (treatment group) treated with combination of Traditional Chinese Medicine (TCM) and Western Medicine. Blood and urine tests were done before treatment and after 8-week treatment. RESULTS: The levels of the main composition of ex- tracellular matrix (MC-ECM), the metabolic enzyme of ECM (ME-ECM) and some cytokines in group B decreased more obviously than those in group A after 8-week treatment. So did the level of 24-hour urine protein. However, Metal matrix protease (MMP)-2 and vascular endothelial growth factor in group B increased more obviously than those in group A after 8-week treatment. No effects on the renal function were found in both groups. CONCLUSION: Our study provided important information on using the combination of TCM with Western Medicine to inhibit the progression of renal fibrosis in patients with IgAN.     

Effect of a clinical pathway to reduce hospitalizations in nursing home residents with pneumonia: a randomized controlled trial

Context  Nursing home residents with pneumonia are frequently hospitalized. Such transfers may be associated with multiple hazards of hospitalization as well as economic costs. Objective  To assess whether using a clinical pathway for on-site treatment of pneumonia and other lower respiratory tract infections in nursing homes could reduce hospital admissions, related complications, and costs. Design, Setting, and Participants  A cluster randomized controlled trial of 680 residents aged 65 years or older in 22 nursing homes in Hamilton, Ontario, Canada. Nursing homes began enrollment between January 2, 2001, and April 18, 2002, with the last resident follow-up occurring July 4, 2005. Residents were eligible if they met a standardized definition of lower respiratory tract infection. Interventions  Treatment in nursing homes according to a clinical pathway, which included use of oral antimicrobials, portable chest radiographs, oxygen saturation monitoring, rehydration, and close monitoring by a research nurse, or usual care. Main Outcome Measures  Hospital admissions, length of hospital stay, mortality, health-related quality of life, functional status, and cost. Results  Thirty-four (10%) of 327 residents in the clinical pathway group were hospitalized compared with 76 (22%) of 353 residents in the usual care group. Adjusting for clustering of residents in nursing homes, the weighted mean reduction in hospitalizations was 12% (95% confidence interval [CI], 5%-18%; P = .001). The mean number of hospital days per resident was 0.79 in the clinical pathway group vs 1.74 in the usual care group, with a weighted mean difference of 0.95 days per resident (95% CI, 0.34-1.55 days; P = .004). The mortality rate was 8% (24 deaths) in the clinical pathway group vs 9% (32 deaths) in the usual care group, with a weighted mean difference of 2.9% (95% CI, –2.0% to 7.9%; P = .23). There were no significant differences between the groups in health-related quality of life or functional status. The clinical pathway resulted in an overall cost savings of US $1016 per resident (95% CI, $207-$1824) treated. Conclusion  Treating residents of nursing homes with pneumonia and other lower respiratory tract infections with a clinical pathway can result in comparable clinical outcomes, while reducing hospitalizations and health care costs. Trial Registration  clinicaltrials.gov Identifier: NCT00157612      

HIV transmission through breastfeeding: a study in Malawi.

CONTEXT: Understanding the risk of human immunodeficiency virus (HIV) transmission through breastfeeding is essential for advising HIV-infected mothers and formulating public health policy recommendations. OBJECTIVE: To measure the frequency, timing, and risk factors of HIV transmission through breast milk. DESIGN: Prospective cohort study conducted between 1994 and 1997, with follow-up of infants through 24 months of age. SETTING: Postnatal clinic of tertiary care hospital, Blantyre, Malawi. PARTICIPANTS: A total of 672 infants (HIV-negative at birth) born to HIV-infected women who had not received antiretroviral drugs during or after pregnancy. MAIN OUTCOME MEASURE: Incidence of HIV in breastfed infants by age and maternal and infant risk factors for HIV transmission, using proportional hazard models to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Forty-seven children became HIV-infected while breastfeeding but none after breastfeeding had stopped. The cumulative infection rate while breastfeeding, from month 1 to the end of months 5, 11,17, and 23, was 3.5%, 7.0%, 8.9%, and 10.3%, respectively. Incidence per month was 0.7% during age 1 to 5 months, 0.6% during age 6 to 11 months, and 0.3% during age 12 to 17 months (P = .01 for trend). The only factors significantly associated with low risk of postnatal HIV transmission in a multivariate model were high maternal parity (RR, 0.23; 95% CI, 0.09-0.56) and older maternal age (RR, 0.44; 95% CI, 0.23-0.84). CONCLUSIONS: Our data suggest that the risk of HIV infection is highest in the early months of breastfeeding, which should be considered in formulating breastfeeding policy recommendations.     

A randomized control trial on interruption of HBV transmission in uterus

Objective To study the interruptive effect of hepatitis B virus (HBV) specific immunolobulin (HBIG) before delivery in attempt to prevent intrauterine transmission of HBV.Methods Nine hundred and eighty HBsAg carrier pregnant women were randomly divided into HBIG group and control group. Each subject in the HBIG group received 200 IU or 400 IU of HBIG intramuscularly at 3, 2 and 1 month before delivery. The subjects in the control group did not receive any specific treatment. All newborn infants received 100 IU of HBIG intramascularty after venous blood samples were taken at birth and 2 weeks after birth, followed by 30 μg plasma-derived HB vaccine or 5 μg recombinant yeast-derived hepatitis B vaccine at 1, 2 and 7 months of age. Blood tests were performed for all the lying-in women and their neonates. Blood specimens were tested for HBsAg and HBeAg by enzyme immunoassay. All infants were followed up for 1 year.Results In the HBIG group, 491 neonates were born to 487 HBV carrier mothers; and in the control group, 496 neonates were born to 493 HBV carrier mothers. The rates of intrauterine transmission in the two groups were 14.3% and 5.7% respectively (χ2=20.280, P&lt;0.001), and the rates of chronic hepatitis B in the two groups were 2.2% and 7.3% respectively (χ2=13.696, P&lt;0.001). The high risk factors of intrauterine HBV infection included HBsAg HBeAg double positive and HBV DNA positive in the peripheral blood of pregnant women.Conclusion HBV infection in the uterus may be interrupted by injecting multiple intramuscular HBIG injections before delivery without causing any side-effects.     

Labor analgesia with ropivacaine added to clonidine: a randomized clinical trial

CONTEXT AND OBJECTIVE: Previous studies have led to speculation that the association between ropivacaine and clonidine might be more effective than ropivacaine alone. We examined the maternal-fetal effects of two pharmacological approaches: a low dose of ropivacaine or a lower dose of ropivacaine plus clonidine for epidural analgesia during labor. DESIGN AND SETTING: Prospective study at Department of Anesthesiology, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista. METHODS: Thirty-two pregnant women in American Society of Anesthesiologists physical status I and II randomly underwent epidural analgesia using 15 ml of ropivacaine 0.125% (R group) or 15 ml of ropivacaine 0.0625% plus 75 microg clonidine (RC group). Pain intensity, sensory block level, latency time, motor block intensity, duration of labor analgesia and duration of epidural analgesia were evaluated. The newborns were evaluated using Apgar scores and the Amiel-Tison method (neurological and adaptive capacity score). RESULTS: There were no statistically significant differences between the groups regarding pain score, sensory block level, duration of epidural analgesia or Apgar score. The latency time, duration of labor analgesia and motor block were R group < RC group. The half-hour and two-hour neurological and adaptive capacity scores were higher in the R group. All of the R group newborns and 75% of the RC group newborns were found to be neurologically healthy at the 24-hour examination. RESULTS: There were no statistically significant differences between the groups regarding pain score, sensory block level, duration of epidural analgesia or Apgar score. The latency time, duration of labor analgesia and motor block were R group < RC group. The half-hour and two-hour neurological and adaptive capacity scores were higher in the R group. All of the R group newborns and 75% of the RC group newborns were found to be neurologically healthy at the 24-hour examination. CONCLUSION: Both low-dose ropivacaine and a lower dose plus clonidine relieved maternal pain during obstetric labor. Newborns of mothers who received only ropivacaine showed better neurological and adaptive capacity scores.     

Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial

Context  Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective  To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer. Design, Setting, and Patients  Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention  Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures  Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results  Among the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse–free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%). Conclusions  In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration  clinicaltrials.gov Identifier: NCT00394511      

Neuropsychological and renal effects of dental amalgam in children: a randomized clinical trial

Context  No randomized trials have been published that address the concern that inhalation of mercury vapor released by amalgam dental restorations causes adverse health effects. Objective  To compare the neuropsychological and renal function of children whose dental caries were restored using amalgam or mercury-free materials. Design and Setting  The New England Children's Amalgam Trial was a 2-group randomized safety trial involving 5 community health dental clinics in Boston, Mass, and 1 in Farmington, Me, between September 1997 and March 2005. Participants and Intervention  A total of 534 children aged 6 to 10 years at baseline with no prior amalgam restorations and 2 or more posterior teeth with caries were randomly assigned to receive dental restoration of baseline and incident caries during a 5-year follow-up period using either amalgam (n=267) or resin composite (n =267) materials. Main Outcome Measures  The primary neuropsychological outcome was 5-year change in full-scale IQ scores. Secondary outcomes included tests of memory and visuomotor ability. Renal glomerular function was measured by creatinine-adjusted albumin in urine. Results  Children had a mean of 15 tooth surfaces (median, 14) restored during the 5-year period (range, 0-55). Assignment to the amalgam group was associated with a significantly higher mean urinary mercury level (0.9 vs 0.6 µg/g of creatinine at year 5, P<.001). After adjusting for randomization stratum and other covariates, no statistically significant differences were found between children in the amalgam and composite groups in 5-year change in full-scale IQ score (3.1 vs 2.1, P = .21). The difference in treatment group change scores was 1.0 (95% confidence interval, –0.6 to 2.5) full-scale IQ score point. No statistically significant differences were found for 4-year change in the general memory index (8.1 vs 7.2, P = .34), 4-year change in visuomotor composite (3.8 vs 3.7, P = .93), or year 5 urinary albumin (median, 7.5 vs 7.4 mg/g of creatinine, P = .61). Conclusions  In this study, there were no statistically significant differences in adverse neuropsychological or renal effects observed over the 5-year period in children whose caries were restored using dental amalgam or composite materials. Although it is possible that very small IQ effects cannot be ruled out, these findings suggest that the health effects of amalgam restorations in children need not be the basis of treatment decisions when choosing restorative dental materials. Trial Registration  clinicaltrials.gov Identifier: NCT00065988