Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

ObjectiveTo analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns.Study designThe original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment.ResultsTwo hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window.ConclusionDespite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives

Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need therapies that cover the continuum of brain injury that spans hours, days, weeks and months after the initial event. Most agents have several therapeutic actions but can be broadly classified under a predominant action (e.g., free radical scavenging, anti-apoptotic, anti-inflammatory, neuroregeneration, and vascular effects). Promising early/secondary phase therapies include Allopurinol, Azithromycin, Exendin-4, Magnesium, Melatonin, Noble gases and Sildenafil. Tertiary phase agents include Erythropoietin, Stem cells and others. We review a selection of promising therapeutic agents on the translational pipeline and suggest a framework for neuroprotection and neurorestoration that targets the evolving injury

Access to Sterile Syringes through San Francisco Pharmacies and the Association with HIV Risk Behavior among Injection Drug Users

Increased options for syringe acquisition and disposal have been associated with reductions in high-risk behaviors. This study determined the extent of pharmacy uptake in accessing syringes among injection drug users (IDUs) and estimated associations between pharmacy uptake and safer injection/disposal practices. Two years after the implementation of California’s Disease Prevention Demonstration Project, which removed restrictions to non-prescription syringe sales through pharmacies with local authorization, IDUs were recruited through street outreach in San Francisco and interviewed regarding recent syringe acquisition, use, and disposal. The sample of 105 persons included a high proportion of men (67%), people of color (49%), and homeless persons (71%). The most common syringe source was a syringe exchange program (SEP) (80%), with pharmacies being accessed by 39% of respondents. The most commonly cited source of disposal was a SEP (65%), with very few reports of pharmacy disposal (2%). Adjusted analysis showed that unsuccessful attempts to purchase syringes at a pharmacy increased the odds of both injecting with a used syringe and giving away a used syringe. Using a SEP decreased the odds of unsafe injection and disposal practices. Thus, 2 years after the initiation of the California Disease Prevention Demonstration Project, results from this small study suggest that SEPs still provide the majority of syringe distribution and disposal services to San Francisco IDUs; however, pharmacies now augment syringe access. In addition, unsafe injection behavior is reported more often among those who do not use these syringe sources. These results are consistent with prior studies in suggesting that increasing the availability of syringes through SEPs and pharmacies, and developing bridges between them, may further reduce syringe-related risk

Pharmacy Participation in Non-Prescription Syringe Sales in Los Angeles and San Francisco Counties, 2007

Increasing sterile syringe access for injection drug users (IDUs) is one way to prevent HIV and hepatitis C virus (HCV) transmission in this population. In 2005, California Senate Bill 1159 allowed counties to adopt the Disease Prevention Demonstration Project (DPDP). Where enacted, the DPDP allows pharmacies that register with the county to sell up to ten syringes to adults without a prescription. In the current study, we describe pharmacy participation in nonprescription syringe sales (NPSS) in two counties in California and examine factors associated with NPSS. Telephone and in-person interviews were conducted in Los Angeles (LA) and San Francisco (SF) with 238 pharmacies in 2007 (n = 67 in SF; n = 171 in LA). Quantitative survey items captured pharmacy registration with the county, pharmacy policies/practices, episodes and conditions of NPSS and refusals to sell, potential negative consequences of NPSS, and staff attitudes regarding HIV and HCV prevention for IDUs. Overall, 42% of pharmacies reported NPSS (28% in LA and 81% in SF), although only 34% had registered with the county (17% in LA and 76% in SF). Many pharmacies required proof of a medical condition (80% in LA and 30% in SF) and refused NPSS if the customer was a suspected IDU (74% in LA, 33% in SF). Few negative consequences of NPSS were reported. In multivariate logistic regression analysis, we found that the odds of NPSS were significantly higher among pharmacists who thought syringe access was important for preventing HIV among IDUs [adjusted odds ratio (AOR) = 2.95; 95% confidence interval (CI) = 1.10–7.92], were chain pharmacies (AOR = 12.5; 95% CI = 4.55–33.33), and were located in SF (AOR = 4.88; 95% CI = 1.94–12.28). These results suggest that NPSS were influenced by pharmacists’ perception. NPSS might be increased through greater educational efforts directed at pharmacists, particularly those in non-chain pharmacies

Early cranial ultrasound findings among infants with neonatal encephalopathy in Uganda: an observational study.

BACKGROUND: In sub-Saharan Africa, the timing and nature of brain injury and their relation to mortality in neonatal encephalopathy (NE) are unknown. We evaluated cranial ultrasound (cUS) scans from term Ugandan infants with and without NE for evidence of brain injury. METHODS: Infants were recruited from a national referral hospital in Kampala. Cases (184) had NE and controls (100) were systematically selected unaffected term infants. All had cUS scans <36 h reported blind to NE status. RESULTS: Scans were performed at median age 11.5 (interquartile range (IQR): 5.2-20.2) and 8.4 (IQR: 3.6-13.5) hours, in cases and controls respectively. None had established antepartum injury. Major evolving injury was reported in 21.2% of the cases vs. 1.0% controls (P < 0.001). White matter injury was not significantly associated with bacteremia in encephalopathic infants (odds ratios (OR): 3.06 (95% confidence interval (CI): 0.98-9.60). Major cUS abnormality significantly increased the risk of neonatal death (case fatality 53.9% with brain injury vs. 25.9% without; OR: 3.34 (95% CI: 1.61-6.95)). CONCLUSION: In this low-resource setting, there was no evidence of established antepartum insult, but a high proportion of encephalopathic infants had evidence of major recent and evolving brain injury on early cUS imaging, suggesting prolonged or severe acute exposure to hypoxia-ischemia (HI). Early abnormalities were a significant predictor of death

Three Years after Legalization of Nonprescription Pharmacy Syringe Sales in California: Where Are We Now?

In January 2005, passage of California Senate Bill 1159 enabled California’s county or city governments to establish disease prevention demonstration projects (DPDPs) through which pharmacies could subsequently register to legally sell up to 10 syringes to adults without a prescription. California’s 61 local health jurisdictions (LHJs) were surveyed annually in 2005–2007 to monitor the progress of DPDP implementation and assess program coverage, facilitators, and barriers. Completed surveys were returned by mail, fax, e-mail, phone, or internet. We analyzed 2007 survey data to describe current DPDP status; data from all years were analyzed for trends in approval and implementation status. By 2007, 17 (27.9%) LHJs approved DPDPs, of which 14 (82.4%) had registered 532 (17.8%) of the 2,987 pharmacies in these 14 LHJs. Although only three LHJs added DPDPs since 2006, the number of registered pharmacies increased 102% from 263 previously reported. Among the LHJs without approved DPDPs in 2007, one (2.3%) was in the approval process, seven (16.3%) planned to seek approval, and 35 (81.4%) reported no plans to seek approval. Of 35 LHJs not planning to seek approval, the top four reasons were: limited health department time (40%) or interest (34%), pharmacy disinterest (31%), and law enforcement opposition (26%). Among eight LHJs pursuing approval, the main barriers were “time management” (13%), educating stakeholders (13%), and enlisting pharmacy participation (13%). The17 LHJs with DPDP represent 52% of California’s residents; they included 62% of persons living with HIV and 59% of IDU-related HIV cases, suggesting that many LHJs with significant numbers of HIV cases have approved DPDPs. Outcome studies are needed to determine whether SB 1159 had the desired impact on increasing syringe access and reducing blood-borne viral infection risk among California IDUs

Efficacy of bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR for detecting neonatal sepsis: a case control study

<p>Abstract</p> <p>Background</p> <p>Neonatal sepsis is difficult to diagnose and pathogens cannot be detected from blood cultures in many cases. Development of a rapid and accurate method for detecting pathogens is thus essential. The main purpose of this study was to identify etiological agents in clinically diagnosed neonatal sepsis using bacterial ribosomal RNA-targeted reverse transcription-quantitative PCR (BrRNA-RT-qPCR) and to conduct comparisons with the results of conventional blood culture. Since BrRNA-RT-qPCR targets bacterial ribosomal RNA, detection rates using this approach may exceed those using conventional PCR.</p> <p>Methods</p> <p>Subjects comprised 36 patients with 39 episodes of suspected neonatal sepsis who underwent BrRNA-RT-qPCR and conventional blood culture to diagnose sepsis. Blood samples were collected aseptically for BrRNA-RT-qPCR and blood culture at the time of initial sepsis evaluation by arterial puncture. BrRNA-RT-qPCR and blood culture were undertaken using identical blood samples, and BrRNA-RT-qPCR was performed using 12 primer sets.</p> <p>Results</p> <p>Positive rate was significantly higher for BrRNA-RT-qPCR (15/39, 38.5%) than for blood culture (6/39, 15.4%; p = 0.0039). BrRNA-RT-qPCR was able to identify all pathogens detected by blood culture. Furthermore, this method detected pathogens from neonates with clinical sepsis in whom pathogens was not detected by culture methods.</p> <p>Conclusions</p> <p>This RT-PCR technique is useful for sensitive detection of pathogens causing neonatal sepsis, even in cases with negative results by blood culture.</p

Parental use of the Internet to seek health information and primary care utilisation for their child: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Using the Internet to seek health information is becoming more common. Its consequences on health care utilisation are hardly known in the general population, in particular among children whose parents seek health information on the Internet. Our objective was to investigate the relationship between parental use of the Internet to seek health information and primary care utilisation for their child.</p> <p>Methods</p> <p>This cross-sectional survey has been carried out in a population of parents of pre-school children in France. The main outcome measure was the self-reported number of primary care consultations for the child, according to parental use of the Internet to seek health information, adjusted for the characteristics of the parents and their child respectively, and parental use of other health information sources.</p> <p>Results</p> <p>A total of 1 068 out of 2 197 questionnaires were returned (response rate of 49%). No association was found between parental use of the Internet to seek health information and the number of consultations within the last 12 months for their child. Variables related to the number of primary care consultations were characteristics of the child (age, medical conditions, homeopathic treatment), parental characteristics (occupation, income, stress level) and consultation of other health information sources (advice from pharmacist, relatives).</p> <p>Conclusion</p> <p>We did not find any relationship between parental use of the Internet to seek health information and primary care utilisation for children. The Internet seems to be used as a supplement to health services rather than as a replacement.</p

Beyond Bacteria: A Study of the Enteric Microbial Consortium in Extremely Low Birth Weight Infants

Extremely low birth weight (ELBW) infants have high morbidity and mortality, frequently due to invasive infections from bacteria, fungi, and viruses. The microbial communities present in the gastrointestinal tracts of preterm infants may serve as a reservoir for invasive organisms and remain poorly characterized. We used deep pyrosequencing to examine the gut-associated microbiome of 11 ELBW infants in the first postnatal month, with a first time determination of the eukaryote microbiota such as fungi and nematodes, including bacteria and viruses that have not been previously described. Among the fungi observed, Candida sp. and Clavispora sp. dominated the sequences, but a range of environmental molds were also observed. Surprisingly, seventy-one percent of the infant fecal samples tested contained ribosomal sequences corresponding to the parasitic organism Trichinella. Ribosomal DNA sequences for the roundworm symbiont Xenorhabdus accompanied these sequences in the infant with the greatest proportion of Trichinella sequences. When examining ribosomal DNA sequences in aggregate, Enterobacteriales, Pseudomonas, Staphylococcus, and Enterococcus were the most abundant bacterial taxa in a low diversity bacterial community (mean Shannon-Weaver Index of 1.02±0.69), with relatively little change within individual infants through time. To supplement the ribosomal sequence data, shotgun sequencing was performed on DNA from multiple displacement amplification (MDA) of total fecal genomic DNA from two infants. In addition to the organisms mentioned previously, the metagenome also revealed sequences for gram positive and gram negative bacteriophages, as well as human adenovirus C. Together, these data reveal surprising eukaryotic and viral microbial diversity in ELBW enteric microbiota dominated bytypes of bacteria known to cause invasive disease in these infants