Health Effects of Wildfire Smoke Exposure.

We review current knowledge on the trends and drivers of global wildfire activity, advances in the measurement of wildfire smoke exposure, and evidence on the health effects of this exposure. We describe methodological issues in estimating the causal effects of wildfire smoke exposures on health and quantify their importance, emphasizing the role of nonlinear and lagged effects. We conduct a systematic review and meta-analysis of the health effects of wildfire smoke exposure, finding positive impacts on all-cause mortality and respiratory hospitalizations but less consistent evidence on cardiovascular morbidity. We conclude by highlighting priority areas for future research, including leveraging recently developed spatially and temporally resolved wildfire-specific ambient air pollution data to improve estimates of the health effects of wildfire smoke exposure.

Autoimmune retinopathy in a patient with smoldering multiple myeloma: a case report.

PURPOSE: Multiple myeloma (MM) is a plasma cell dyscrasia leading to proliferation of monoclonal plasma cells. Ocular involvement in multiple myeloma is uncommon but can occur. The ocular manifestations of MM may include the cornea, uvea, and retinal vasculature. We present a rare case of autoimmune retinopathy associated with smoldering MM. CASE: A 76-year-old female with no significant past medical or ocular history presented with four months of worsening vision, difficulty with night driving, and loss of peripheral vision. Examination was notable for pallor of the optic nerves and vascular attenuation. Visual field testing demonstrated significant and progressive field loss in both eyes. An electroretinogram was extinguished under all conditions. Serum protein electrophoresis showed a significant elevation of IgG with an M-spike, and a subsequent bone marrow biopsy was performed showing 12.5% plasma cells, consistent with the diagnosis of MM. CAR antibody testing was positive for anti-enolase, anti-GAPDH, and anti-Rab6 antibodies, consistent with autoimmune retinopathy. DISCUSSION: Autoimmune retinopathy associated with MM is exceedingly rare. Management of this condition is challenging, as treatment of the underlying disease does not often lead to improvement in visual symptoms. Ultimately, visual prognosis is very poor, and both patients and clinicians should be aware of the guarded visual potential. CONCLUSION: The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients.

A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial.

BACKGROUND: Management of type 1 diabetes is challenging. We compared outcomes using a commercially available hybrid closed-loop system versus a new investigational system with features potentially useful for adolescents and young adults with type 1 diabetes. METHODS: In this multinational, randomised, crossover trial (Fuzzy Logic Automated Insulin Regulation [FLAIR]), individuals aged 14-29 years old, with a clinical diagnosis of type 1 diabetes with a duration of at least 1 year, using either an insulin pump or multiple daily insulin injections, and glycated haemoglobin (HbA1c) levels of 7·0-11·0% (53-97 mmol/mol) were recruited from seven academic-based endocrinology practices, four in the USA, and one each in Germany, Israel, and Slovenia. After a run-in period to teach participants how to use the study pump and continuous glucose monitor, participants were randomly assigned (1:1) using a computer-generated sequence, with a permuted block design (block sizes of two and four), stratified by baseline HbA1c and use of a personal MiniMed 670G system (Medtronic) at enrolment, to either use of a MiniMed 670G hybrid closed-loop system (670G) or the investigational advanced hybrid closed-loop system (Medtronic) for the first 12-week period, and then participants were crossed over with no washout period, to the other group for use for another 12 weeks. Masking was not possible due to the nature of the systems used. The coprimary outcomes, measured with continuous glucose monitoring, were proportion of time that glucose levels were above 180 mg/dL (>10·0 mmol/L) during 0600 h to 2359 h (ie, daytime), tested for superiority, and proportion of time that glucose levels were below 54 mg/dL (<3·0 mmol/L) calculated over a full 24-h period, tested for non-inferiority (non-inferiority margin 2%). Analysis was by intention to treat. Safety was assessed in all participants randomly assigned to treatment. This trial is registered with ClinicalTrials.gov, NCT03040414, and is now complete. FINDINGS: Between June 3 and Aug 22, 2019, 113 individuals were enrolled into the trial. Mean age was 19 years (SD 4) and 70 (62%) of 113 participants were female. Mean proportion of time with daytime glucose levels above 180 mg/dL (>10·0 mmol/L) was 42% (SD 13) at baseline, 37% (9) during use of the 670G system, and 34% (9) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] -3·00% [95% CI -3·97 to -2·04]; p<0·0001). Mean 24-h proportion of time with glucose levels below 54 mg/dL (<3·0 mmol/L) was 0·46% (SD 0·42) at baseline, 0·50% (0·35) during use of the 670G system, and 0·46% (0·33) during use of the advanced hybrid closed-loop system (mean difference [advanced hybrid closed-loop system minus 670G system] -0·06% [95% CI -0·11 to -0·02]; p<0·0001 for non-inferiority). One severe hypoglycaemic event occurred in the advanced hybrid closed-loop system group, determined to be unrelated to study treatment, and none occurred in the 670G group. INTERPRETATION: Hyperglycaemia was reduced without increasing hypoglycaemia in adolescents and young adults with type 1 diabetes using the investigational advanced hybrid closed-loop system compared with the commercially available MiniMed 670G system. Testing an advanced hybrid closed-loop system in populations that are underserved due to socioeconomic factors and testing during pregnancy and in individuals with impaired awareness of hypoglycaemia would advance the effective use of this technology FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.

A rare case of a clinically significant anti-M alloantibody in a heart transplant recipient.

INTRODUCTION: Anti-M antibodies are usually inactive at physiologic temperatures (37 °C). Rarely, these antibodies have been reported to react at physiologic temperatures, resulting in clinically significant hemolytic transfusion reactions or hemolytic disease of the fetus and newborn. PATIENT AND METHODS: We describe a case of an acute hemolytic transfusion reaction due to an anti-M alloantibody reacting at physiologic temperatures in a critically ill patient. RESULTS: Proper identification and management of anti-M antibody-mediated acute hemolysis rapidly improved and stabilized her hemoglobin. CONCLUSION: Differentiation between anti-M antibody-mediated acute hemolysis and its differential diagnoses is of critical importance to guide therapeutic decisions in these rare clinical scenarios.

COVID-19 Pandemic Mental Health Challenges: Patients and Providers.

Interviews with 15 Tennessee Advanced Practice Registered Nurses early in the COVID-19 pandemic revealed a major theme of mental health challenges unrelated to the primary study purpose. Without direct prompts, 13 out of 15 interviewees mentioned mental health issues among patients and 14 of the 15 interviewees discussed provider mental health problems. A secondary analysis of interview transcripts revealed three themes associated with mental health challenges: general barriers to mental health care, patient-specific concerns, and provider issues. Responding to the new and worsening mental health and substance use disorders revealed by informants and cited in the literature is an urgent priority.

Frontal white matter lesions in Alzheimer's disease are associated with both small vessel disease and AD-associated cortical pathology.

Cerebral white matter lesions (WML) encompass axonal loss and demyelination and are assumed to be associated with small vessel disease (SVD)-related ischaemia. However, our previous study in the parietal lobe white matter revealed that WML in Alzheimer's disease (AD) are linked with degenerative axonal loss secondary to the deposition of cortical AD pathology. Furthermore, neuroimaging data suggest that pathomechanisms for the development of WML differ between anterior and posterior lobes with AD-associated degenerative mechanism driving posterior white matter disruption, and both AD-associated degenerative and vascular mechanisms contributed to anterior matter disruption. In this pilot study, we used human post-mortem brain tissue to investigate the composition and aetiology of frontal WML from AD and non-demented controls to determine if frontal WML are SVD-associated and to reveal any regional differences in the pathogenesis of WML. Frontal WML tissue sections from 40 human post-mortem brains (AD, n = 19; controls, n = 21) were quantitatively assessed for demyelination, axonal loss, cortical hyperphosphorylated tau (HPτ) and amyloid-beta (Aß) burden, and arteriolosclerosis as a measure of SVD. Biochemical assessment included Wallerian degeneration-associated protease calpain and the myelin-associated glycoprotein to proteolipid protein ratio as a measure of ante-mortem ischaemia. Arteriolosclerosis severity was found to be associated with and a significant predictor of frontal WML severity in both AD and non-demented controls. Interesting, frontal axonal loss was also associated with HPτ and calpain levels were associated with increasing Aß burden in the AD group, suggestive of an additional degenerative influence. To conclude, this pilot data suggest that frontal WML in AD may result from both increased arteriolosclerosis and AD-associated degenerative changes. These preliminary findings in combination with previously published data tentatively indicate regional differences in the aetiology of WML in AD, which should be considered in the clinical diagnosis of dementia subtypes: posterior WML maybe associated with degenerative mechanisms secondary to AD pathology, while anterior WML could be associated with both SVD-associated and degenerative mechanisms.

Thirdhand smoke associations with the gut microbiomes of infants admitted to a neonatal intensive care unit: An observational study.

INTRODUCTION: Microbiome differences have been found in adults who smoke cigarettes compared to non-smoking adults, but the impact of thirdhand smoke (THS; post-combustion tobacco residue) on hospitalized infants' rapidly developing gut microbiomes is unexplored. Our aim was to explore gut microbiome differences in infants admitted to a neonatal ICU (NICU) with varying THS-related exposure. METHODS: Forty-three mother-infant dyads (household member[s] smoke cigarettes, n = 32; no household smoking, n = 11) consented to a carbon monoxide-breath sample, bedside furniture nicotine wipes, infant-urine samples (for cotinine [nicotine's primary metabolite] assays), and stool collection (for 16S rRNA V4 gene sequencing). Negative binomial regression modeled relative abundances of 8 bacterial genera with THS exposure-related variables (i.e., household cigarette use, surface nicotine, and infant urine cotinine), controlling for gestational age, postnatal age, antibiotic use, and breastmilk feeding. Microbiome-diversity outcomes were modeled similarly. Bayesian posterior probabilities (PP) ≥75.0% were considered meaningful. RESULTS: A majority of infants (78%) were born pre-term. Infants from non-smoking homes and/or with lower NICU-furniture surface nicotine had greater microbiome alpha-diversity compared to infants from smoking households (PP ≥ 75.0%). Associations (with PP ≥ 75.0%) of selected bacterial genera with urine cotinine, surface nicotine, and/or household cigarette use were evidenced for 7 (of 8) modeled genera. For example, lower Bifidobacterium relative abundance associated with greater furniture nicotine (IRR<0.01 [<0.01, 64.02]; PP = 87.1%), urine cotinine (IRR = 0.08 [<0.01,2.84]; PP = 86.9%), and household smoking (IRR<0.01 [<0.01, 7.38]; PP = 96.0%; FDR p < 0.05). CONCLUSIONS: THS-related exposure was associated with microbiome differences in NICU-admitted infants. Additional research on effects of tobacco-related exposures on healthy infant gut-microbiome development is warranted.

A polar filter in DNA polymerases prevents ribonucleotide incorporation.

The presence of ribonucleotides in DNA can lead to genomic instability and cellular lethality. To prevent adventitious rNTP incorporation, the majority of the DNA polymerases (dPols) possess a steric filter. The dPol named MsDpo4 (Mycobacterium smegmatis) naturally lacks this steric filter and hence is capable of rNTP addition. The introduction of the steric filter in MsDpo4 did not result in complete abrogation of the ability of this enzyme to incorporate ribonucleotides. In comparison, DNA polymerase IV (PolIV) from Escherichia coli exhibited stringent selection for deoxyribonucleotides. A comparison of MsDpo4 and PolIV led to the discovery of an additional polar filter responsible for sugar selectivity. Thr43 represents the filter in PolIV and this residue forms interactions with the incoming nucleotide to draw it closer to the enzyme surface. As a result, the 2'-OH in rNTPs will clash with the enzyme surface, and therefore ribonucleotides cannot be accommodated in the active site in a conformation compatible with productive catalysis. The substitution of the equivalent residue in MsDpo4-Cys47, with Thr led to a drastic reduction in the ability of the mycobacterial enzyme to incorporate rNTPs. Overall, our studies evince that the polar filter serves to prevent ribonucleotide incorporation by dPols.

Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial.

BACKGROUND: Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone. METHODS: In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA1c) concentration of 7·5% or higher (≥58 mmol/mol) and 11% or lower (≤97 mmol/mol), and had been using the same insulin regimen for the previous 3 months. Exclusion criteria included body-mass index of 45 kg/m2 or higher; severe cardiac, hepatic, or renal impairment; and more than two severe hypoglycaemic events in the past year. Eligible participants were randomly assigned (1:1), with randomisation blocked within each site, to either d-Nav and health-care professional support (intervention group) or health-care professional support alone (control group). Both groups were contacted seven times (three face-to-face and four phone visits) during 6 months of follow-up. The primary objective was to compare average change in HbA1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycaemic events. The primary objective and safety were assessed in the intention-to-treat population. We used Student's t test to assess the primary outcome for statistical significance. This study was registered with ClinicalTrials.gov, number NCT02424500. FINDINGS: Between Feb 2, 2015, and March 17, 2017, 236 patients were screened for eligibility, of whom 181 (77%) were enrolled and randomly assigned to the intervention (n=93) and control (n=88) groups. At baseline, mean HbA1c was 8·7% (SD 0·8; 72 mmol/mol [SD 8·8]) in the intervention group and 8·5% (SD 0·8; 69 mmol/mol [SD 8·8]) in the control group. The mean decrease in HbA1c from baseline to 6 months was 1·0% (SD 1·0; 11 mmol/mol [SD 11]) in the intervention group, and 0·3% (SD 0·9; 3·3 mmol/mol [9·9]) in the control group (p<0·0001). The frequency of hypoglycaemic events per month was similar between the groups (0·29 events per month [SD 0·48] in the intervention group vs 0·29 [SD 1·12] in the control group; p=0·96). INTERPRETATION: The combination of automated insulin titration guidance with support from health-care professionals offers superior glycaemic control compared with support from health-care professionals alone. Such a solution facilitated safe and effective insulin titration in a large group of patients with type 2 diabetes, and now needs to be evaluated across large health-care systems to confirm these findings and study cost-effectiveness. FUNDING: US National Institutes of Health, National Institute of Digestive and Kidney Diseases.

Prevalence of Potentially Pathogenic Antibiotic-Resistant Aeromonas spp. in Treated Urban Wastewater Effluents versus Recipient Riverine Populations: a 3-Year Comparative Study.

Antibiotic resistance continues to be an emerging threat both in clinical and environmental settings. Among the many causes, the impact of postchlorinated human wastewater on antibiotic resistance has not been well studied. Our study compared antibiotic susceptibility among Aeromonas spp. in postchlorinated effluents to that of the recipient riverine populations for three consecutive years against 12 antibiotics. Aeromonas veronii and Aeromonas hydrophila predominated among both aquatic environments, although greater species diversity was evident in treated wastewater. Overall, treated wastewater contained a higher prevalence of nalidixic acid-, trimethoprim-sulfamethoxazole (SXT)-, and tetracycline-resistant isolates, as well as multidrug-resistant (MDR) isolates compared to upstream surface water. After selecting for tetracycline-resistant strains, 34.8% of wastewater isolates compared to 8.3% of surface water isolates were multidrug resistant, with nalidixic acid, streptomycin, and SXT being the most common. Among tetracycline-resistant isolates, efflux pump genes tetE and tetA were the most prevalent, though stronger resistance correlated with tetA. Over 50% of river and treated wastewater isolates exhibited cytotoxicity that was significantly correlated with serine protease activity, suggesting many MDR strains from effluent have the potential to be pathogenic. These findings highlight that conventionally treated wastewater remains a reservoir of resistant, potentially pathogenic bacterial populations being introduced into aquatic systems that could pose a threat to both the environment and public health.IMPORTANCE Aeromonads are Gram-negative, asporogenous rod-shaped bacteria that are autochthonous in fresh and brackish waters. Their pathogenic nature in poikilotherms and mammals, including humans, pose serious environmental and public health concerns especially with rising levels of antibiotic resistance. Wastewater treatment facilities serve as major reservoirs for the dissemination of antibiotic resistance genes (ARGs) and resistant bacterial populations and are, thus, a potential major contributor to resistant populations in aquatic ecosystems. However, few longitudinal studies exist analyzing resistance among human wastewater effluents and their recipient aquatic environments. In this study, considering their ubiquitous nature in aquatic environments, we used Aeromonas spp. as bacterial indicators of environmental antimicrobial resistance, comparing it to that in postchlorinated wastewater effluents over 3 years. Furthermore, we assessed the potential of these resistant populations to be pathogenic, thus elaborating on their potential public health threat.

Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians.

BACKGROUND: Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. OBJECTIVES: The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated. METHODS: Serum or plasma (n = 27) and brain samples from the frontal cortex (FC; n = 46) and the temporal cortex (TC; n = 33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use. RESULTS: MK-4 was the predominant vitamer in both FC (mean ± SD = 4.92 ± 2.31 pmol/g, ≥89.15% ± 5.09% of total VK) and TC (4.60 ± 2.11 pmol/g, ≥89.71% ± 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users. CONCLUSIONS: Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.

The Effect of Inorganic Salt on Disintegration of Tablets with High Loading of Amorphous Solid Dispersion Containing Copovidone.

PURPOSE: While including amorphous solid dispersion (ASD) in tablet formulations is increasingly common, tablets containing high ASD loading are associated with slow disintegration, which presents a challenge to control pill burden for less potent compounds. METHODS: We use a model ASD, composed of a hydrophobic drug with copovidone and a non-ionic surfactant, to explore formulation options that can prevent slow disintegration. RESULTS: In addition to the ASD loading, the pH of the disintegration medium and the inclusion of inorganic salts in the tablet also have an impact on the tablet disintegration time. Certain kosmotropic salts, when added in the formulation, can significantly accelerate tablet disintegration, though the rank order in their effectiveness does not exactly follow the Hofmeister series at pH 1.8. The particle size and dissolution rate of the salt can contribute to its overall effectiveness. CONCLUSION: We provided a mechanistic explanation of the disintegration process: fast-dissolving kosmotropic salt results in a concentrated salt solution inside the restrained tablet matrix, thus inhibiting the dissolution of copovidone and preventing polymer gelling which is the main cause leading the slow disintegration. The outcome of this study has enabled the design of a higher ASD loading platform formulation for copovidone based ASD. Graphical Abstract MicroCT aids the mechanistic understanding of the role of inorganic salt in the tablet disintegration of amorphous solid dispersion based formulation.

Trans-hiatal repair for Oesophageal and Junctional perforation: a case series.

BACKGROUND: Oesophageal perforation is a life-threatening condition that requires urgent intervention. Surgical repair is recommended within 24 h of onset to minimise mortality risk, traditionally via an open thoracotomy or a laparotomy. Primary oesophageal repair via a laparoscopic trans-hiatal approach has been seldomly reported due to concerns of inadequate eradication of soilage in the mediastinum and pleural space, as well as poor access and an increased operative time in an unwell population. CASE PRESENTATION: We report a case series of 3 oesophageal and junctional perforations with varying presentations, demonstrating how the laparoscopic trans-hiatal approach can be used successfully to manage oesophageal perforations. CONCLUSIONS: Laparoscopic trans-hiatal repair is an attractive option for oesophageal and junctional perforations, in haemodynamically stable surgical candidates, in the absence of gross contamination of the thoracic cavity.

Postoperative Infections Associated With Prolonged Spinal Cord Stimulation Trial Duration (PROMISE RCT).

INTRODUCTION: In the PROMISE study, a multinational randomized controlled trial (RCT) of the effectiveness of spinal cord stimulation (SCS) with multicolumn surgical leads as a treatment of low back pain, clinicians followed their usual practice. An early, unplanned safety analysis revealed that the infection rate in Belgium (5/23), where trial duration was a median 21.5 days, was significantly higher than the 1/64 rate observed in the other study countries (median 5.8 days, p < 0.01). This report reviews infections observed in the PROMISE study after study completion. MATERIALS AND METHODS: For all infections related to SCS, we used descriptive statistics and tests of independent variables to analyze potentially contributing factors (age, sex, coexisting medical conditions, tobacco use, lead type, and trial duration) between subjects with infections versus those without. Cumulative incidence curves were created using the Kaplan-Meier method and compared between the two strata using a log-rank test. RESULTS: Among nine (5.2%) infections in 174 subjects trialed, the only significant contributing factor to infection was trial duration: median 21 days (range 3-56) for those with infection vs. six days (1-41) for those without (p = 0.001; Wilcoxon rank-sum test). The cumulative incidence of infection for subjects trialed >10 days was 24.1% vs. 1.4% for subjects trialed ≤10 days (p < 0.001). After the protocol was amended to limit trial duration to 10 days, 14 infection-free trials were performed in Belgium. CONCLUSIONS: Although not part of the preplanned analysis, our observation supports the hypothesis of a cause-effect relationship between trial duration and the risk of infection and the conclusion that prolonged SCS trials should be avoided.

Laparoscopic management of chylous ascites posthiatal hernia repair with Toupet fundoplication.

We present a case of chylous ascites in a 69-year-old man 5 months after a laparoscopic Toupet fundoplication (posterior 270°). This was successfully treated with laparoscopic ligation of tissue adjacent to the right crus. Laparoscopic ligation is a management option that should be considered after this rare complication, offering rapid results.

Declining Trends of Pneumococcal Meningitis in Gambian Children After the Introduction of Pneumococcal Conjugate Vaccines.

BACKGROUND: Acute bacterial meningitis remains a major cause of childhood mortality in sub-Saharan Africa. We document findings from hospital-based sentinel surveillance of bacterial meningitis among children <5 years of age in The Gambia, from 2010 to 2016. METHODS: Cerebrospinal fluid (CSF) was collected from children admitted to the Edward Francis Small Teaching Hospital with suspected meningitis. Identification of Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae was performed by microbiological culture and/or polymerase chain reaction where possible. Whole genome sequencing was performed on pneumococcal isolates. RESULTS: A total of 438 children were admitted with suspected meningitis during the surveillance period. The median age of the patients was 13 (interquartile range, 3-30) months. Bacterial meningitis was confirmed in 21.4% (69/323) of all CSF samples analyzed. Pneumococcus, meningococcus, and H. influenzae accounted for 52.2%, 31.9%, and 16.0% of confirmed cases, respectively. There was a significant reduction of pneumococcal conjugate vaccine (PCV) serotypes, from 44.4% in 2011 to 0.0% in 2014, 5 years after PCV implementation. The majority of serotyped meningococcus and H. influenzae belonged to meningococcus serogroup W (45.5%) and H. influenzae type b (54.5%), respectively. Meningitis pathogens were more frequently isolated during the dry dusty season of the year. Reduced susceptibility to tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol was observed. No resistance to penicillin was found. CONCLUSIONS: The proportion of meningitis cases due to pneumococcus declined in the post-PCV era. However, the persistence of vaccine-preventable meningitis in children aged <5 years is a major concern and demonstrates the need for sustained high-quality surveillance.

ISCEV extended protocol for the stimulus-response series for the dark-adapted full-field ERG b-wave.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum protocol for clinical testing but encourages more extensive testing where appropriate. This ISCEV extended protocol describes an extension of the ISCEV full-field ERG standard, in which methods to record and evaluate the growth of the dark-adapted (DA) ERG b-wave with increasing stimulus energy are described. The flashes span a range that includes the weakest flash required to generate a reliable DA ERG b-wave and that required to generate a maximal b-wave amplitude. The DA ERG b-wave stimulus-response series (also known historically as the "intensity-response" or "luminance-response" series) can more comprehensively characterize generalized rod system function than the ISCEV standard ERG protocol and may be of diagnostic or prognostic value in disorders that cause generalized rod system dysfunction.

Cardiovascular health and cognitive functioning among centenarians: a comparison between the Tokyo and Georgia centenarian studies.

ABSTRACTObjectives:Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan. DESIGN, SETTING, AND PARTICIPANTS: This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians. MEASUREMENTS: Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters. RESULTS: The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein). CONCLUSION: For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.

Exploring the science, safety, and benefits of air care products: perspectives from the inaugural air care summit.

Seventy-one percent of US households purchase air care products. Air care products span a diverse range of forms, including scented aerosol sprays, pump sprays, diffusers, gels, candles, and plug-ins. These products are used to eliminate indoor malodors and to provide pleasant scent experiences. The use of air care products can lead to significant benefits as studies have shown that indoor malodor can cause adverse effects, negatively impacting quality of life, hygiene, and the monetary value of homes and cars, while disproportionately affecting lower income populations. Additionally, studies have also shown that scent can have positive benefits related to mood, stress reduction, and memory enhancement among others. Despite the positive benefits associated with air care products, negative consumer perceptions regarding the safety of air care products can be a barrier to their use. During the inaugural Air Care Summit, held on 18 May 2018 in the Washington, DC, metropolitan area, multidisciplinary experts including industry stakeholders, academics, and scientific and medical experts were invited to share and assess the existing data related to air care products, focusing on ingredient and product safety and the benefits of malodor removal and scent. At the Summit's completion, a panel of independent experts representing the fields of pulmonary medicine, medical and clinical toxicology, pediatric toxicology, basic science toxicology, occupational dermatology and experimental psychology convened to review the data presented, identify potential knowledge gaps, and suggest future research directions to further assess the safety and benefits of air care products.

A Quality Study to Explore Rationale for Pregnant Women to Decline Transvaginal Cervical Length Screening.

OBJECTIVES: To identify patient rationale for pregnant women to decline transvaginal cervical length screening. METHODS: Survey data from 511 women presenting for second-trimester anatomy and transvaginal cervical length sonography were collected during a 4-month period from September 2016 to January 2017. Each patient completed a medical questionnaire that includes demographic and obstetric history data and a survey to document their acceptance or declination of transvaginal cervical length screening. RESULTS: Of the 511 women included in the study, 5.9% (n = 30) declined transvaginal cervical length screening. Demographic characteristics and risk factors for prematurity were similar between those who accepted and declined. The sonographer performing the study was significantly associated with declination of transvaginal cervical length screening (P < .001), with 4 of 13 sonographers accounting for 83.3% of all declinations. The most frequently reported reasons for declining the transvaginal cervical length screening were feeling that it was not needed (47%; n = 14) and not feeling prepared for the transvaginal sonography (27%; n = 8). CONCLUSION: The findings of this study indicate that the sonographer performing transvaginal cervical length screening may be associated with declination. The most common reasons patients cited for declining included not feeling that the study was needed and not feeling prepared for the procedure. Increased sonographer education and sonographer use of a scripted approach when discussing the procedure with patients may improve patient acceptance.