The Effects of Hyperbaric Oxygen Treatment on Verbal Scores in Children With Autism Spectrum Disorder: A Retrospective Trial.

Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects millions worldwide. Suggested pathophysiology includes cerebral hypoperfusion, inflammation, mitochondrial and immune dysregulation, and oxidative stress. Debate exists concerning the benefit of hyperbaric oxygen therapy (HBOT) in treating ASD and its impacts on verbal behavior. The present study directly assesses the impacts of HBOT treatments on verbal behavior using a novel and unique manner.  Materials and methods A two-group quasi-experimental trial using a pretest and a posttest was designed to retrospectively assess (n = 65) any association between HBOT and change in verbal scores in children (n = 65) with ASD. All children completed two verbal tests six months apart, either the Verbal Behavior Milestones Assessment and Placement Program (VBMAPP) or the Assessment of Basic Language and Learning Skills (ABLLS), based on their developmental age. The control cohort received applied behavior analysis (ABA) without HBOT. The experimental cohort received ABA and a minimum of 40 HBOT treatments, breathing 100% oxygen at 2.0 atmosphere absolute (ATA) for 60 minutes. Results Sixty-five children were included, of which 32 received HBOT (mean (M) = 5.1, standard deviation (SD) = 2.93), with an age range of two to 17 years. More than 63% of the subjects had an autism severity level of three. The 23 children administered VBMAPP who received HBOT showed substantial mean differences with high effect sizes (ESs) (-0.743 to -1.65) and a total score (TS) ES equal to -1.23 as measured by Cohen's d. There was a statistically significant improvement (p < 0.05) in all VBMAPP milestone domains and TS. TS change from baseline versus those in the non-HBOT (Control-ABA) group (n=12) was 46.41 ± 20.14 vs 14.42 ± 6.99; p < 0.0001, ES = -1.23. The 30 children administered the ABLLS showed substantial mean difference (TS) change from baseline 268.89 ± 182.05 vs 190.81 ± 135.26 and exhibited small to medium (-.114 to -.773) ESs with a TS ES = -0.487. Due to the high within-group variability (low statistical power) within the ABLLS cohort, there was a non-significant mean difference between the control (ABA) and experimental (ABA + HBO2) groups' difference scores (p > 0.2024), despite the medium (TS) ES. Conclusions The child cohorts administered the VBMAPP and the ABLLS demonstrated substantial improvements between the non-HBOT (control-ABA) and HBOT (experimental-ABA + HBO2) groups as measured by the significant mean differences and small to large ESs. Simply put, the children in the experimental cohort acquired more verbal skills than their counterparts in the control group.

Safety and Pharmacokinetics Following Oral or Intravenous Lefamulin in Adults With Cystic Fibrosis.

PURPOSE: Methicillin-resistant Staphylococcus aureus infections are increasing in prevalence in patients with cystic fibrosis (CF) and are associated with worsening lung function and increased mortality. Lefamulin is a pleuromutilin antimicrobial approved to treat community-acquired bacterial pneumonia based on potent in vitro activity and clinical efficacy. This Phase I, open-label, randomized crossover study assessed the safety and pharmacokinetic profile of oral and intravenous (IV) lefamulin in adults with CF. METHODS: The study comprised 2 dosing periods in which adults with CF (N = 13) received a single dose of lefamulin via a 150-mg IV infusion or 600-mg immediate-release orally administered tablet, separated by a 4- to 7-day washout period. Pharmacokinetic and safety parameters were assessed after lefamulin treatment. FINDINGS: Single doses of lefamulin administered via oral tablet or IV infusion resulted in comparable drug exposure, and sputum analysis suggested rapid penetration of lefamulin into the lung. Comparison of the present results with those obtained from prior single-dose studies of healthy volunteers indicate no meaningful difference in the pharmacokinetic properties of lefamulin in patients with CF. Treatment-emergent adverse events were consistent with previous reports, and the majority were mild in severity. IMPLICATIONS: These results show similar lefamulin pharmacokinetic and safety profiles between patients with CF and healthy volunteers receiving the same oral and IV doses, suggesting no need for lefamulin dose adjustment in patients with CF and indicating the potential of lefamulin as therapy for lung infections in patients with CF. CLINICALTRIALS: gov identifier: NCT05225805.

Two-Way Crossover Phase 1 Bioequivalence and Safety Studies in Healthy Adults for a Ready-to-Use, Room-Temperature, Liquid-Stable Glucagon Administered by Autoinjector, Prefilled Syringe, or Vial and Syringe.

OBJECTIVE: To demonstrate bioequivalence and safety for a ready-to-use room-temperature liquid-stable glucagon administered subcutaneously (SC) through a glucagon autoinjector (GAI) or a glucagon vial and syringe kit (GVS), versus a glucagon prefilled syringe (G-PFS). METHODS: Healthy adults (N = 32) were randomly assigned to receive 1-mg glucagon as GAI or G-PFS, and then as the alternative three to seven days later. Other healthy adults (N = 40) were randomly assigned to receive 1-mg glucagon as GVS or G-PFS, and then as the alternative two days later. Samples for plasma glucagon were obtained through 240 minutes after glucagon injection. Bioequivalence was declared when the geometric mean estimate ratio of the area under-the-concentration-versus-time curve from 0 to 240 minutes (AUC0-240) and maximum concentration (Cmax) for plasma glucagon between treatment groups was contained within the bounds of 80% and 125%. Adverse events (AEs) were recorded. RESULTS: The 90% confidence intervals (CIs) for AUC0-240 and Cmax geometric mean ratios for G-PFS to GAI and GVS to G-PFS were contained within the bounds 80% to 125% (G-PFS:GAI AUC0-240 95.05%, 119.67% and Cmax 88.01%, 120.24%; GVS:G-PFS AUC0-240 87.39%, 100.66% and Cmax 89.08%, 106.08%). At least one AE occurred in 15.6% (5/32) participants with GAI, 25% (18/72) with G-PFS, and 32.5% (13/40) with GVS. Sixty-nine of 73 (94.5%) AEs were mild, and none were serious. Nausea was the most common (33/73 [45%]). CONCLUSIONS: Bioequivalence and safety were established after 1 mg of this ready-to-use room-temperature liquid-stable glucagon, administered SC to healthy adults, by autoinjector, prefilled syringe, or vial and syringe kit.

Comparison of a ready-to-use liquid glucagon injection administered by autoinjector to glucagon emergency kit for the symptomatic relief of severe hypoglycemia: two randomized crossover non-inferiority studies.

INTRODUCTION: To prevent medical sequelae of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A ready-to-use, liquid stable glucagon, administered subcutaneously by glucagon autoinjector (GAI), Gvoke HypoPen (glucagon injection; Xeris Pharmaceuticals), was evaluated for rescue treatment of severe hypoglycemia. RESEARCH DESIGN AND METHODS: Two phase III, randomized, controlled, blinded, non-inferiority crossover studies were conducted in 161 adults with type 1 diabetes to compare 1 mg doses of GAI versus glucagon emergency kit (GEK) for treating insulin-induced severe hypoglycemia. Efficacy was evaluated as either a return of plasma glucose to >70 mg/dL (3.9 mmol/L) or increase ≥20 mg/dL (1.1 mmol/L) from a baseline glucose of <50 mg/dL (2.9 mmol/L), within 30 min of dosing. RESULTS: For successful plasma glucose recovery within 30 min, treatment with GAI was non-inferior to GEK. Treatment with GAI was non-inferior to GEK for a plasma glucose >70 mg/dL (3.9 mmol/L) or neuroglycopenic symptom relief within 30 min. From administration of glucagon, the mean time to achieve plasma glucose >70 mg/dL (3.9 mmol/L) or increase ≥20 mg/dL (1.1 mmol/L) was 13.8±5.6 min for GAI and 10.0±3.6 min for GEK. This mean time does not account for the significantly shorter (p<0.0001) drug preparation and administration time for GAI (27.3±19.7 s) versus GEK (97.2±45.1 s). The incidence of treatment emergent adverse events was comparable in both groups. CONCLUSIONS: A ready-to-use GAI was non-inferior to GEK, with a similar tolerability profile. GAI is an effective, safe, and well-tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK. TRIAL REGISTRATION NUMBERS: NCT02656069 and NCT03439072.

spa Typing and Multilocus Sequence Typing Show Comparable Performance in a Macroepidemiologic Study of Staphylococcus aureus in the United States.

A number of molecular typing methods have been developed for characterization of Staphylococcus aureus isolates. The utility of these systems depends on the nature of the investigation for which they are used. We compared two commonly used methods of molecular typing, multilocus sequence typing (MLST) (and its clustering algorithm, Based Upon Related Sequence Type [BURST]) with the staphylococcal protein A (spa) typing (and its clustering algorithm, Based Upon Repeat Pattern [BURP]), to assess the utility of these methods for macroepidemiology and evolutionary studies of S. aureus in the United States. We typed a total of 366 clinical isolates of S. aureus by these methods and evaluated indices of diversity and concordance values. Our results show that, when combined with the BURP clustering algorithm to delineate clonal lineages, spa typing produces results that are highly comparable with those produced by MLST/BURST. Therefore, spa typing is appropriate for use in macroepidemiology and evolutionary studies and, given its lower implementation cost, this method appears to be more efficient. The findings are robust and are consistent across different settings, patient ages, and specimen sources. Our results also support a model in which the methicillin-resistant S. aureus (MRSA) population in the United States comprises two major lineages (USA300 and USA100), which each consist of closely related variants.

Kericho CLinic-based ART Diagnostic Evaluation (CLADE): design, accrual, and baseline characteristics of a randomized controlled trial conducted in predominately rural, district-level, HIV clinics of Kenya.

BACKGROUND: Prospective clinical trial data regarding routine HIV-1 viral load (VL) monitoring of antiretroviral therapy (ART) in non-research clinics of Sub-Saharan Africa are needed for policy makers. METHODS: CLinic-based ART Diagnostic Evaluation (CLADE) is a randomized, controlled trial (RCT) evaluating feasibility, superiority, and cost-effectiveness of routine VL vs. standard of care (clinical and immunological) monitoring in adults initiating dual nucleoside reverse transcriptase inhibitor (NRTI)+non-NRTI ART. Participants were randomized (1:1) at 7 predominately rural, non-research, district-level clinics of western Kenya. Descriptive statistics present accrual patterns and baseline cohort characteristics. RESULTS: Over 15 months, 820 adults enrolled at 7 sites with 86-152 enrolled per site. Monthly site enrollment ranged from 2-92 participants. Full (100%) informed consent compliance was independently documented. Half (49.9%) had HIV diagnosed through voluntary counseling and testing. Study arms were similar: mostly females (57.6%) aged 37.6 (SD = 9.0) years with low CD4 (166 [SD = 106]) cells/m3). Notable proportions had WHO Stage III or IV disease (28.7%), BMI <18.5 kg/m2 (23.1%), and a history of tuberculosis (5.6%) or were receiving tuberculosis treatment (8.2%) at ART initiation. In the routine VL arm, 407/409 (99.5%) received baseline VL (234,577 SD = 151,055 copies/ml). All participants received lamivudine; 49.8% started zidovudine followed by 38.4% stavudine and 11.8% tenofovir; and, 64.4% received nevirapine as nNRTI (35.6% efavirenz). CONCLUSIONS: A RCT can be enrolled successfully in rural, non-research, resource limited, district-level clinics in western Kenya. Many adults presenting for ART have advanced HIV/AIDS, emphasizing the importance of universal HIV testing and linkage-to-care campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT01791556.

Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent postconcussion symptoms: a randomized clinical trial.

IMPORTANCE: Improvement has been anecdotally observed in patients with persistent postconcussion symptoms (PCS) after mild traumatic brain injury following treatment with hyperbaric oxygen (HBO). The effectiveness of HBO as an adjunctive treatment for PCS is unknown to date. OBJECTIVES: To compare the safety of and to estimate the efficacy for symptomatic outcomes from standard PCS care alone, care supplemented with HBO, or a sham procedure. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, sham-controlled clinical trial of 72 military service members with ongoing symptoms at least 4 months after mild traumatic brain injury enrolled at military hospitals in Colorado, North Carolina, California, and Georgia between April 26, 2011, and August 24, 2012. Assessments occurred before randomization, at the midpoint, and within 1 month after completing the interventions. INTERVENTIONS: Routine PCS care was provided in specialized clinics. In addition, participants were randomized 1:1:1 to 40 HBO sessions administered at 1.5 atmospheres absolute (ATA), 40 sham sessions consisting of room air at 1.2 ATA, or no supplemental chamber procedures. MAIN OUTCOMES AND MEASURES: The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) served as the primary outcome measure. A change score of at least 2 points on the RPQ-3 subscale (range, 0-12) was defined as clinically significant. Change scores from baseline were calculated for the RPQ-3 and for the total RPQ. Secondary measures included additional patient-reported outcomes and automated neuropsychometric testing. RESULTS: On average, participants had sustained 3 lifetime mild traumatic brain injuries; the most recent occurred 23 months before enrollment. No differences were observed between groups for improvement of at least 2 points on the RPQ-3 subscale (25% in the no intervention group, 52% in the HBO group, and 33% in the sham group; P = .24). Compared with the no intervention group (mean change score, 0.5; 95% CI, -4.8 to 5.8; P = .91), both groups undergoing supplemental chamber procedures showed improvement in symptoms on the RPQ (mean change score, 5.4; 95% CI, -0.5 to 11.3; P = .008 in the HBO group and 7.0; 95% CI, 1.0-12.9; P = .02 in the sham group). No difference between the HBO group and the sham group was observed (P = .70). Chamber sessions were well tolerated. CONCLUSIONS AND RELEVANCE: Among service members with persistent PCS, HBO showed no benefits over sham compressions. Both intervention groups demonstrated improved outcomes compared with PCS care alone. This finding suggests that the observed improvements were not oxygen mediated but may reflect nonspecific improvements related to placebo effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01306968.

Field-user acceptability evaluation of a new stick camouflage face paint formulation with and without the insect repellent DEET.

Two newly designed formulations of stick camouflage face paint, one with 30% N,N-diethyl-3-methylbenzamide (DEET) and the other without DEET, were evaluated for acceptability among soldiers upon completion of normal military field training exercises. A total of 156 soldiers participated and completed a self-administered survey answering questions about product acceptability, packaging, and ease of use. Results of the study indicated that soldiers found stick formulations, with and without DEET, to be acceptable for use (62.9% and 83.7%, respectively). This data will be used by the Program Management Office at the U.S. Army Medical Materiel Development Activity to support a request to the Armed Forces Pest Management Board to assign a National Stock Number.

Molecular characterization of Staphylococcus aureus in the United States 2004-2008 reveals the rapid expansion of USA300 among inpatients and outpatients.

To assess the clonal structure of Staphylococcus aureus in the United States, we performed a molecular epidemiological study of 1,055 S. aureus isolates from a nationally representative clinical isolate collection from 2004-2008. Resistant and susceptible isolates were typed with multilocus sequence typing, tested for the presence of Panton-Valentine leukocidin (PVL), and serotyped. USA300 (multilocus sequence typing clonal complex 8, PVL positive, and methicillin-resistant) was the most frequently isolated clone, expanding from 12% of all isolates in 2004 to 38% in 2006. The USA300 clone increased significantly in frequency among both outpatients and inpatients. USA300 increased in both skin and soft-tissue and invasive infection isolates. The second most frequently observed clone was clonal complex 5, PVL-negative, and methicillin-resistant, and its frequency was stable from 2004-2008. The methicillin-susceptible S. aureus in the study was polyclonal, and decreased in frequency as it was replaced by USA300.

Association of HIV neutralizing antibody with lower viral load after treatment interruption in a prospective trial (A5170).

OBJECTIVE: We investigated the impact of neutralizing antibodies (NAbs) on CD4 T-cell count and viral load in a cohort of HAART recipients who underwent extended structured treatment interruption. DESIGN: Substudy of NAb in the AIDS Clinical Trials Group 5170 trial. METHODS: Early plasma samples from 50 volunteers who discontinued HAART were evaluated in a peripheral blood mononuclear cell-based neutralization assay against a panel of four subtype B primary isolates. RESULTS: We found that high-titer (90% inhibitory dose > 500) NAb against two or more isolates was associated with reduced viral load (P = 0.003 at 12-week posttreatment interruption). This effect faded with time, losing significance (P = 0.161) by study conclusion. Participants possessing the highest NAb levels against individual isolates appeared more likely to have lower viral loads with the association gaining significance against the R5-tropic primary isolate US1 (P = 0.005). There was no association between broader neutralization and CD4 T-cell slope over time. CONCLUSION: The data suggest that high-titer NAb responses at the time of treatment interruption are associated with reduced viral load over time, but not CD4(+) T-cell decline.

Prevalence and sequence variation of panton-valentine leukocidin in methicillin-resistant and methicillin-susceptible staphylococcus aureus strains in the United States.

Panton-Valentine leukocidin (PVL), encoded by the lukSF-PV genes, is a putative virulence factor and marker for community-associated methicillin-resistant Staphylococcus aureus. Here we report the prevalence of PVL among a representative sample of 1,055 S. aureus infection isolates from the United States and describe the sequence variation of the lukSF-PV genes. We performed multilocus sequence typing (MLST) on all isolates and sequenced fragments of the lukSF-PV genes from a sample of 86 isolates. We assigned isolates to a PVL R or H sequence type based on a polymorphism that results in an amino acid change from arginine (R) to histidine (H). Overall, we found that 36% of S. aureus isolates were positive for lukSF-PV. Among the 86 we typed, we identified 72 R variants and 14 H variants. Among the 47 methicillin-resistance S. aureus (MRSA) isolates, 43 harbored the R variant, and among the 39 methicillin-susceptible S. aureus (MSSA) isolates, 29 harbored the R variant. Almost all (97%) of the R variants were found in MLST clonal complex 8 (CC8), while the H variant was broadly distributed among 6 CCs. Within CC8, all 38 MRSA (USA300) and all 28 MSSA isolates harbored the R variant. Of the 20 isolates from blood and the lower respiratory tract, 19 (95%) harbored the R variant. While the R variant had been linked primarily to USA300 MRSA, we found that all CC8 MSSA isolates also contained the R variant, suggesting that some strains of USA300 may have lost methicillin resistance as an adaptation in the community.

Traffic Impacts on PM(2.5) Air Quality in Nairobi, Kenya.

Motor vehicle traffic is an important source of particulate pollution in cities of the developing world, where rapid growth, coupled with a lack of effective transport and land use planning, may result in harmful levels of fine particles (PM(2.5)) in the air. However, a lack of air monitoring data hinders health impact assessments and the development of transportation and land use policies that could reduce health burdens due to outdoor air pollution. To address this important need, a study of traffic-related PM(2.5) was carried out in the city of Nairobi, Kenya, a model city for sub-Saharan Africa, in July 2009. Sampling was carried out using portable filter-based air samplers carried in backpacks by technicians on weekdays over two weeks at several sites in and around Nairobi ranging from high-traffic roadways to rural background. Mean daytime concentrations of PM(2.5) ranged from 10.7 at the rural background site to 98.1 µg/m(3) on a sidewalk in the central business district. Horizontal dispersion measurements demonstrated a decrease in PM(2.5) concentration from 128.7 to 18.7 µg/m(3) over 100 meters downwind of a major intersection in Nairobi. A vertical dispersion experiment revealed a decrease from 119.5 µg/m(3) at street level to 42.8 µg/m(3) on a third-floor rooftop in the central business district. Though not directly comparable to air quality guidelines, which are based on 24-hour or annual averages, the urban concentrations we observed raise concern with regard to public health and related policy. Taken together with survey data on commuting patterns within Nairobi, these results suggest that many Nairobi residents are exposed on a regular basis to elevated concentrations of fine particle air pollution, with potentially serious long-term implications for health.

HIV awareness and condom use among female sex workers in Afghanistan: implications for intervention.

There is little information about HIV awareness or condom use among female sex workers (FSWs) in Afghanistan. The purpose of this cross-sectional study was to assess HIV awareness, knowledge, and condom use among FSWs in three Afghan cities. FSWs residing in Jalalabad, Kabul, and Mazar-i-Sharif were recruited through outreach programs and completed an interviewer-administered questionnaire and rapid tests for hepatitis B surface antigen, HIV, syphilis, and hepatitis C virus. Logistic regression identified factors associated with HIV awareness, comprehensive HIV knowledge (knowledge that HIV cannot be detected by sight, that condoms prevent HIV, and rejection of local misconceptions about HIV transmission), and consistent condom use (use with every sex act) with clients in the last six months. Of 520 participants, 76.9% had no formal education and 37.7% lived outside Afghanistan in the last five years. Nearly half (44.2%) were aware of HIV but, of these, only 17.4% (N = 40) had comprehensive HIV knowledge. There were significant differences by site; FSWs in Jalalabad were more likely to be aware of HIV but FSWs in Kabul were more likely to have correct HIV knowledge and use condoms consistently with clients. Consistent client condom use was reported by 11.5% (N = 60) and was independently associated with having more clients per month (AOR = 1.99, 95% CI: 1.04-3.81). In conclusion, comprehensive HIV knowledge and consistent condom use with clients are low among Afghan FSWs in these cities. Efforts to reach this population should focus on relaying accurate information and expanding condom use with clients.

Evaluation of efficacy and duration of the stick camouflage face paint with 30% deet against mosquitoes in Belize.

A combination of insect repellent, N,N-diethyl-3-methylbenzamide (deet), with camouflage face paint in a newly designed stick formulation was evaluated on human volunteers under field conditions in Belize during February 2007. The formulation provided over 90% protection against mosquitoes for 8 hours and at least 80% protection for 12 hours, with 100% protection for 2 to 4 hours after application.

NIH-Supported National Islet Transplantation Registry.

An estimated 300,000 to 500,000 cases of type 1 diabetes exist today in the United States. Despite strict monitoring and attempts at control, people with type 1 diabetes still face the prospect of diminished health and earlier death than the general population. Islet transplantation offers an alternative to insulin usage and a potential treatment for type 1 diabetes mellitus. There are more than 30 islet transplant centers in the world focusing their efforts on the challenges and methods of this procedure. As the field of islet transplantation matures and the number of islet transplants performed increases, detailed analyses on factors that predict patient and graft survival are needed. This increased amount of data will allow for a better understanding of the safety and efficacy of islet transplantation. In response to the need for more complete information in the field, the National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring the North American Collaborative Islet Transplant Registry (CITR). The mission of CITR is to expedite progress and promote safety in islet/beta-cell transplantation through the collection, analysis, and communication of comprehensive and current data on all islet/beta-cell transplants performed in North America. Compiling and analyzing data from all transplant centers in North America will accelerate the identification of both critical risk factors and key determinants of success, and thereby guide transplant centers in developing and refining islet/beta-cell transplant protocols, leading to an advancement in the field of islet transplantation. Participation in CITR is voluntary, and more than 22 transplant centers have been invited to join. Seven centers are actively participating in CITR, with an additional 11 centers in the process of joining. Both an executive committee and a scientific advisory committee guide CITR. All islet transplants performed in North America since January 1, 1996, are captured by the CITR database. Through an electronic, Internet-based data capture system, quality control procedures, and minimization of duplicate efforts at the transplant center, the most relevant and succinct information are entered. From these data a comprehensive report will be published annually. In addition, special analyses will be performed and published periodically.