Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial

Background Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. Methods This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is “definite or probable relapse” within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O’Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock’s to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. Discussion This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. Trial registration Clinical Trials Registry India CTRI/2017/09/009743. Registered on 13 September 2017.

The Optimum Duration of Flushing Dental Unit Waterlines for Microbial Removal

This study aims to evaluate the optimum duration of flushing dental unit waterlines (DUWLs) in Universiti Sains Islam Malaysia (USIM) dental polyclinics for removal of heterotrophic bacteria. Water samples were obtained from triple air syringes at each dental chair from oral surgery clinic, outpatient clinic and polyclinic 17 at Faculty of Dentistry, USIM after 16 and 64 hours of not operating the dental units as baseline samples. This is followed by sampling after continuous flushing at 30 seconds, 1 minute, 2 minutes and 3 minutes of flushing duration. The levels of heterotrophic plate count (HPC) for each flushing duration were determined by quantification of colony forming units (CFUs) after cultivation of samples on plate count agar (PCA), R2A agar and 5% sheep blood agar (SBA). Statistically, there was no significant reduction in CFUs of HPC for all flushing duration compared to baseline (P > 0.05) with the most notable HPC reducing level after 1 minute and 3 minutes of flushing DUWLs. However, HPC level at USIM dental clinics is still exceeding the recommendation by Centers for Disease Control and Prevention (CDC) which should be less than 500 CFU/mL. The existing method of controlling DUWLs contamination in USIM dental clinics is only by flushing DUWLs 1 minute every morning prior to dental treatment as recommended by Malaysian Dental Council (MDC) without the use of chemical germicides. Thus, the flushing method alone is not reliable to reduce the number of microorganisms in the DUWLs.

Therapeutic hypercapnia for prevention of secondary ischemia after severe subarachnoid hemorrhage: physiological responses to continuous hypercapnia

Temporary hypercapnia has been shown to increase cerebral blood flow (CBF) and might be used as a therapeutical tool in patients with severe subarachnoid hemorrhage (SAH). It was the aim of this study was to investigate the optimum duration of hypercapnia. This point is assumed to be the time at which buffer systems become active, cause an adaptation to changes of the arterial partial pressure of carbon dioxide (PaCO2) and annihilate a possible therapeutic effect. In this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO2) was increased to a target range of 55 mmHg for 120 min by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15 min. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. Under continuous hypercapnia (PaCO2 of 53.17 ± 5.07), CBF was significantly elevated between 15 and 120 min after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 32% was noted at 45 min after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. CBF and StiO2 reproducibly increased by controlled hypercapnia in all patients. After 45 min, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. It is concluded that 45 min might be the optimum duration for a therapeutic use and may provide an optimal balance between the benefits of hypercapnia and risks of a negative rebound effect after return to normal ventilation parameters.Trial registration: The study was approved by the institutional ethics committee (AZ 230/14) and registered at ClinicalTrials.gov (Trial-ID: NCT01799525). Registered 01/01/2015.

Factors Associated with Duration of Breastfeeding in Bangladesh: Evidence from Bangladesh Demographic and Health Survey 2014

Background: Breastfeeding for optimum duration is one of the most effective ways to reduce infant morbidity and mortality and confirm expected growth and development of children. The aim of this study was to find out the effect of socio-demo­graphic and anthropometric determinants on duration of breast­feeding among Bangladeshi mothers.Methods: The data was extracted from the Bangladesh Demographic and Health Survey (BDHS)-2014. A total of 3541 married non–pregnant Bangladeshi mothers in reproductive age who had at least one child aged 6-36 months were included in this study. Independent sample t-test and analysis of variance (ANOVA) were used to find the significance difference in duration of breastfeeding between two and more than two groups respectively. Multiple linear regression model was utilized to determine the effect of some quantitative variables on duration of breastfeeding. Results: This study raveled that the mean and median duration of breastfeeding among Bangladeshi mothers was 18.91 (95% CI: 18.65-19.17) and 19.00 months respectively. Independent sample t-test and ANOVA showed that duration of breastfeeding among Bangladeshi mothers was significantly influenced by (i) ANC service, (ii) religion, (iii) mode of delivery, (iv) parents’ education, (v) geographical location and (vi) household wealth quintile. Multiple regression analysis demonstrated that mothers’ age, mothers’ body mass index, total number of children and mothers’ age at first birth were important predictors of duration of breastfeeding.Conclusions: Healthcare providers and decision makers can consider these findings to make plan for counseling of mothers and family members to promote optimum duration of breastfeeding practice in first two years of baby’s life.

Factors Associated with Duration of Breastfeeding in Bangladesh: Evidence from Bangladesh Demographic and Health Survey 2014

Background: Breastfeeding for optimum duration is one of the most effective ways to reduce infant morbidity and mortality and confirm expected growth and development of children. The aim of this study was to find out the effect of socio-demo­graphic and anthropometric determinants on duration of breast­feeding among Bangladeshi mothers.Methods: The data was extracted from the Bangladesh Demographic and Health Survey (BDHS)-2014. A total of 3541 married non–pregnant Bangladeshi mothers in reproductive age who had at least one child aged 6-36 months were included in this study. Independent sample t-test and analysis of variance (ANOVA) were used to find the significance difference in duration of breastfeeding between two and more than two groups respectively. Multiple linear regression model was utilized to determine the effect of some quantitative variables on duration of breastfeeding. Results: This study raveled that the mean and median duration of breastfeeding among Bangladeshi mothers was 18.91 (95% CI: 18.65-19.17) and 19.00 months respectively. Independent sample t-test and ANOVA showed that duration of breastfeeding among Bangladeshi mothers was significantly influenced by (i) ANC service, (ii) religion, (iii) mode of delivery, (iv) parents’ education, (v) geographical location and (vi) household wealth quintile. Multiple regression analysis demonstrated that mothers’ age, mothers’ body mass index, total number of children and mothers’ age at first birth were important predictors of duration of breastfeeding.Conclusions: Healthcare providers and decision makers can consider these findings to make plan for counseling of mothers and family members to promote optimum duration of breastfeeding practice in first two years of baby’s life.