Latent TB treatment regimens in 2023: Wetmore TB clinic in New Orleans.

The USPSTF has updated Latent TB Infection (LTBI) screening and treatment recommendations in 2023; describing treatment courses, side effects and benefits associated with each regimen. Overall, rifampin-containing shortened regimens are the preferred modality for LTBI treatment. A recent study in 2023 evaluated adherence and tolerance of the isoniazid(INH) + rifapentine(RPT), or "3HP" regimen and identified patient groups that may be at higher risk for non-completion of this regimen. It emphasized the need for targeted education at the beginning of treatment, to avoid early discontinuation. Our experience in New Orleans demonstrated that the 3HP is well-tolerated, with higher completion rates than other LTBI regimens. Utilizing a retrospective chart review model, we reviewed 756 patients who were treated for LTBI over a two-year period from 1/2021--12/2022. The three possible treatment regimens included isoniazid (INH) alone, rifampin (RIF) alone, or INH + RPT (3HP). Of these regimens, the highest completion rate was in the 3HP group, despite literature suggesting this regimen is difficult to tolerate. Our experience suggests that this may still be an efficacious regimen that is well-tolerated if there is good access to clinicians to discuss mitigating side effects. More data is needed to determine factors that led to the success or failure for each regimen. Our clinic does have increased availability of nursing and medical staff to discuss side effects and answer questions, which may have contributed to our relatively higher success rate. In addition, we applied the review recommendations to our patient population, and would recommend the consideration of diabetes, heavy alcohol use, and tobacco use as risk factors for patients that would benefit from LTBI screening and treatment.

Disease Trajectories in the Revised Hammersmith Scale in a Cohort of Untreated Patients with Spinal Muscular Atrophy types 2 and 3.

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterised by progressive motor function decline. Motor function is assessed using several functional outcome measures including the Revised Hammersmith Scale (RHS). Objective: In this study, we present longitudinal trajectories for the RHS in an international cohort of 149 untreated paediatric SMA 2 and 3 patients (across 531 assessments collected between March 2015 and July 2019). Methods: We contextualise these trajectories using both the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM). At baseline, this cohort included 50% females and 15% of patients had undergone spinal fusion surgery. Patient trajectories were modelled using a natural cubic spline with age, sex, and random effects for each patient. Results: RHS and HFMSE scores show similar trends over time in this cohort not receiving disease modifying therapies. The results confirm the strong correlation between the RHS and RULM previously observed in SMA types 2 and 3a. Scoliosis surgery is associated with a reduction of 3 points in the RHS, 4.5 points in the HFMSE for the SMA 2 population, and a reduction of 11.8 points in the RHS, and 13.4 points in the HFMSE for the SMA 3a populations. When comparing the RHS and RULM, there is a lower correlation in the type 3a's than the type 2 patients. In the SMA 2 population, there is no significant difference between the sexes in either the RHS or HFMSE trajectories. There is no significant difference in the RULM trajectory in the SMA 2 or 3a participants by sex. Conclusions: This study demonstrates that the RHS could be used in conjunction with other functional measures such as the RULM to holistically detect SMA disease progression. This will assist with fully understanding changes that occur with treatments, further defining trajectories and therapy outcomes.

Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom.

Background: Real-world data on the efficacy and safety of onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) are needed, especially to overcome uncertainties around its use in older and heavier children. This study evaluated the efficacy and safety of OA in patients with SMA type 1 in the UK, including patients ≥2 years old and weighing ≥13.5 kg. Methods: This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements. Findings: Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion: 10 [range, 0.6-89] months; median weight: 7.86 [range, 3.2-20.2] kg; duration of follow-up: 3-22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged <6 months had a 13.9 points higher gain in CHOP-INTEND score than patients ≥2 years (95% CI, 6.8-21.0; P < 0.001). Asymptomatic thrombocytopenia (71/99 patients; 71.7%), asymptomatic troponin-I elevation (30/89 patients; 33.7%) and transaminitis (87/99 patients; 87.9%) were reported. No thrombotic microangiopathy was observed. Median steroid treatment duration was 97 (range, 28-548) days with dose doubled in 35/99 patients (35.4%). There were 22.5-fold increased odds of having a transaminase peak >100 U/L (95% CI, 2.3-223.7; P = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2-209.2; P = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported. Interpretation: OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients. Funding: Novartis Innovative Therapies AG provided a grant for independent medical writing services.

Assessment of the upper limb function, strength, and mobility in treatment-naive children with spinal muscular atrophy Types 2 and 3.

INTRODUCTION/AIMS: Current upper limb assessments in pediatric spinal muscular atrophy (SMA) may not adequately capture change with disease progression. Our aim was to examine the relationship between motor function, strength, and hand/finger mobility of the upper limb in treatment-naïve children with SMA Types 2 and 3 to assess new methods to supplement current outcomes. METHODS: The Revised Upper Limb Module (RULM), grip and pinch strength, and hand/finger mobility data were collected from 19 children with SMA Types 2 and 3 aged 5.2-16.9 years over a year. RESULTS: A median loss between 0.5 and 2.5 points in the RULM was seen across all SMA subgroups with the biggest median loss recorded between 10 and 14 years of age. The grip strength loss was -0.06 kg (-4.69 to 3.49; IQR, 1.21); pinch improvement of 0.05 (-0.65 to 1.27; IQR, 0.48); hand/finger mobility test improvement of 4 points (-24 to 14; IQR, 6.75) for the whole cohort. Significant correlations were found between the RULM and grip strength (p < .001), RULM and pinch strength (p < .001), RULM and revised Brooke (p < .001), grip strength and pinch strength (p < .001). DISCUSSION: The combined use of the RULM, dynamometry, and hand mobility provide insight about correlations between function and strength in children with SMA. The RULM and grip strength assessments captured a significant decline in upper limb function, whereas the pinch and finger/hand mobility showed an improvement over the course of 1 year and these results should be considered for future studies.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Quantifying Variability in Motor Function in Duchenne Muscular Dystrophy: UK Centiles for the NorthStar Ambulatory Assessment, 10 m Walk Run Velocity and Rise from Floor Velocity in GC Treated Boys.

Background Boys with Duchenne Muscular Dystrophy (DMD) display heterogeneous motor function trajectory in clinics, which represents a significant obstacle to monitoring. OBJECTIVE: In this paper, we present the UK centiles for the North Star Ambulatory Assessment (NSAA), the 10 m walk/run time (10MWR) and velocity (10MWRV), and the rise from floor time (RFF) and velocity (RFFV) created from a cohort of glucocorticoid treated DMD boys between the age of 5 and 16 years. METHODS: Participants were included from the UK NorthStar registry if they had initiated steroids (primarily deflazacorts/prednisolone, intermittent/daily) and were not enrolled in an interventional trial. Assessments were included if the participant had a complete NSAA, the timed tests had been completed or the corresponding items were 0, or the participant was recorded as non-ambulant, in which case the NSAA was assumed 0. RESULTS: We analysed 3987 assessments of the NSAA collected from 826 participants. Of these, 1080, 1849 and 1199 were imputed as 0 for the NSAA, RFFV and 10MWRV respectively. The 10th, 25th, 50th, 75th and 90th centiles were presented. The NSAA centiles showed a peak score of 14, 20, 26, 30 and 32 respectively, with loss of ambulation at 10.7, 12.2 and 14.3 years for the 25th, 50th and 75th centiles, respectively. The centiles showed loss of rise from floor at 8.6, 10.1 and 11.9 years and a loss of 10MWR of 0 at 8.9, 10.3 and 13.8 years for the 25th, 50th and 75th centiles, respectively. The centiles were pairwise less correlated than the raw scores, suggesting an increased ability to detect variability in the DMD cohort. CONCLUSIONS: The NSAA, 10MWR and RFF centiles may provide insights for clinical monitoring of DMD boys, particularly in late ambulatory participants who are uniformly declining. Future work will validate the centiles in national and international natural history cohorts.

Association between fluoride exposure in drinking water and cognitive deficits in children: A pilot study.

Fluoride (F) exposure in drinking water may lead to reduced cognitive function among children; however, findings largely remain inconclusive. In this pilot study, we examined associations between a range of chronic F exposures (low to high: 0.4 to 15.5 mg/L) in drinking water and cognition in school-aged children (5-14 years, n = 74) in rural Ethiopia. Fluoride exposure was determined from samples of community-based drinking water wells and urine. Cognitive performance was measured using: 1) assessments of ability to draw familiar objects (donkey, house, and person), and 2) a validated Cambridge Neuropsychological Test Automated Battery's (CANTAB) Paired Associate Learning (PAL), which examines memory and new learning and is closely associated with hippocampus function of the brain. Associations between F and cognitive outcomes were evaluated using regression analysis, adjusting for demographic, health status, and other covariates. The median (range) of water and urine F levels was 7.6 (0.4-15.5 mg/L) and 6.3 (0.5-15.7 mg/L), respectively; these measures were strongly correlated (r = 0.74), indicating that water is the primary source of F exposure. Fluoride in drinking water was negatively associated with cognitive function, measured by both drawing and CANTAB test performance. Inverse relationships were also found between F and drawing objects task scores, after adjusting for covariates (p < 0.05). Further analysis using CANTAB PAL tasks in the children confirmed that F level in drinking water was positively associated with the number of errors made by children (p < 0.01), also after adjusting for covariates (p < 0.05). This association between water F and total errors made became markedly stronger as PAL task difficulty increased. Fluoride exposure was also inversely associated with other PAL tasksthe number of patterns reached, first attempt memory score and mean errors to success. These findings provide supportive evidence that high F exposures may be associated with cognitive deficits in children. Additional well-designed studies are critically needed to establish the neurotoxicity of F in children and adults exposed to both low levels known to protect dental caries, as well as excess F levels in drinking water.

Determining minimal clinically important differences in the North Star Ambulatory Assessment (NSAA) for patients with Duchenne muscular dystrophy.

The North Star ambulatory assessment (NSAA) is a functional motor outcome measure in Duchenne muscular dystrophy (DMD), widely used in clinical trials and natural history studies, as well as in clinical practice. However, little has been reported on the minimal clinically important difference (MCID) of the NSAA. The lack of established MCID estimates for NSAA presents challenges in interpreting the significance of the results of this outcome measure in clinical trials, natural history studies and clinical practice. Combining statistical approaches and patient perspectives, this study estimated MCID for NSAA using distribution-based estimates of 1/3 standard deviation (SD) and standard error of measurement (SEM), an anchor-based approach, with six-minute walk distance (6MWD) as the anchor, and evaluation of patient and parent perception using participant-tailored questionnaires. The MCID for NSAA in boys with DMD aged 7 to 10 years based on 1/3 SD ranged from 2.3-2.9 points, and that on SEM ranged from 2.9-3.5 points. Anchored on the 6MWD, the MCID for NSAA was estimated as 3.5 points. When the impact on functional abilities was considered using participant response questionnaires, patients and parent perceived a complete loss of function in a single item or deterioration of function in one to two items of the assessment as an important change. Our study examines MCID estimates for total NSAA scores using multiple approaches, including the impact of patient and parent perspective on within scale changes in items based on complete loss of function and deterioration of function, and provides new insight on evaluation of differences in these widely used outcome measure in DMD.

A Changing Landscape for Lifelong Learning in Health Globally.

On 25 July 2022, the Continuing Professional Development (CPD) Special Interest Group of the Association for Medical Education in Europe came together to open up discussions during a live webinar on 'Exploring the Evolution of CPD'. The objective was to bring together global medical educators to consider perspectives of CPD from the role of global lifelong learners, the role of educators and the role of education providers and health regulators. The landscape of CPD is evolving, and the roles of each key player must include specific actions for facilitated change. Delivering competency outcomes-based learning, fit for purpose, to lifelong learners in health will require (1) learner agency, (2) leadership from educators and (3) providers of lifelong learning to come together to improve delivery of CPD that leads to meaningful change in practice care delivery.

2-Year Change in Revised Hammersmith Scale Scores in a Large Cohort of Untreated Paediatric Type 2 and 3 SMA Participants.

The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale-Expanded (HFMSE). These change scores were considered by SMA type, motor function, and baseline RHS score. We consider a new transitional group, spanning crawlers, standers, and walkers-with-assistance, and analyse that alongside non-sitters, sitters, and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. In the weakest patients, we are most able to detect positive change in the RHS in the under-5 age group, whereas in the stronger patients, we are most able to detect decline in the RHS in the 8-13 age group. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items.

Characteristics of Prognostic Statements During Family Conferences of Critically Ill Children.

OBJECTIVES: Discussion of prognosis is an essential component of decision-making family conferences in critical care. We do not know how clinicians convey prognosis to families of critically ill children. We, therefore, aimed to evaluate the frequency of prognostic statements and the message and meaning conveyed through each statement during PICU family conferences. DESIGN: Retrospective, mixed-methods study. SETTING: PICU of a single quaternary medical center. PATIENTS: Critically ill children and their families participating in PICU family conferences of critical medical decision-making. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 72 transcripts from audio-recorded PICU family conferences to identify prognostic statements. Descriptive, thematic content analysis was used to elucidate the message and meaning of each prognostic statement. Prognosis was not discussed in 26% (19/72) of family conferences. Of the other (53/72) conferences where prognostic statements were made, 60% (67/112) of statements conveyed a message (i.e., prognostic medical information) and a meaning (i.e., anticipated impact on patient/family). "Messages" of prognostic statements fell within eight themes: uncertain recovery, delayed recovery, progressive decline, escalation of support, attributable complications, no progress, irreversible, and probability of death. "Meanings" of prognostic statements fell within six themes: restoration of health, activities of daily living, additional equipment, prolonged care needs, brain dysfunction, and death. Broadly, clinicians discussed prognostic information in three categories: loss of Time (i.e., prolonged care needs), Function (i.e., additional medical equipment), or Cure (i.e., death). CONCLUSIONS: Nearly in half of discussions (32/72, 44%) where families were asked to make critical medical decisions, clinicians did not provide a prognostic statement including a message and meaning. When discussed, prognostic information was conveyed in three categories: loss of time, function, or cure. Providing families context in this framework, particularly in times of uncertainty, may improve the family's ability to make informed, value-driven medical decisions for their child.

"Essential One Day and Forgotten the Next": Perceptions of Ohio's Early Childhood Workforce on Their Exclusion from the Educator Phase of COVID-19 Vaccine Distribution.

This study explores Ohio Early Childhood and Care (ECEC) workers' perspectives about different prioritization for COVID-19 vaccine distribution between Ohio educators employed in ECEC and prek-12 settings. Days after Ohio's shutdown, ECEC programs began reopening for children of essential workers, and by June 2020 all ECEC programs could reopen with enhanced mitigation strategies, while the prek-12 workforce remained remote as they cautiously returned in-person ranging from 2 to 9 months later. Ohio was 1 of 4 states that, despite contrary Center for Disease Control guidance, excluded ECEC workers from the phase of vaccine distribution in which prek-12 workers were eligible. Data on ECEC employee perceptions of this difference were collected via anonymous online questionnaire from 194 ECEC workers. Qualitative analysis revealed six themes: 1. Participants compared themselves to prek-12, 2. believe they are valuable, 3. disagreed with the decision, 4. felt undervalued compared to prek-12, 5. felt exploited, and 6. suffered mental health effects. ECEC workers' perspectives are valuable and should be included in decisions impacting them.

Defining Objective Measures of Physician Stress in Simulated Critical Communication Encounters.

This study had three aims: 1) quantify the difference in stress levels between low and high stress roles during simulated critical communication encounters using objective physiologic data (heart rate variability [HRV]) and subjective measures (State-Trait Anxiety Inventory [STAI]), 2) define the relationship between subjective and objective measures of stress, and 3) define the impact of trainee preparedness and reported self-efficacy on stress levels. DESIGN: Mixed methods simulation-based study. SETTING: Single center. PATIENTS: Pediatric critical care fellows and faculty (n = 12). INTERVENTIONS: Subjects participated in six simulated scenarios in both high stress "hot seat" and low stress "observer" roles. MEASUREMENTS AND MAIN RESULTS: Subjective stress was measured using the STAI at baseline and after each scenario. Objective stress was measured continuously using a wearable biometric device measuring HRV. Previous residency communication training and self-confidence surrounding various communication topics were collected via questionnaire. Significant changes in subjective (STAI) and objective stress (HRV) measurements in the low- versus high-stress roles were observed. STAI scores increased 8 points during low stress and 12 points during high stress role (p = 0.021) compared with baseline. Two specific HRV markers, root mean square of successive differences between normal heartbeats, a marker of parasympathetic tone, and the low frequency/high frequency (LF/HF) ratio, a marker of sympathetic activation, were significantly correlated with STAI levels (-0.032, p = 0.001; 1.030, p = 0.002, respectively). Participants who reported increased confidence in discussing code status had a significant decrease in stress response (measured via LF/HF ratio) during both the observer (p = 0.033) and hot seat roles (p = <0.001). CONCLUSIONS: Communicating life-altering news in a simulated environment is a stressful experience. This stress results in physiologic changes that can be measured continuously using HRV. HRV measurement may serve as a novel method in evaluating the effectiveness of communication training programs and measuring future stress-reduction interventions.

Vulnerability of Inexperience: A Qualitative Exploration of Physician Grief and Coping after Impactful Pediatric Patient Deaths.

Background: Caring for dying patients can result in burnout, stress, and emotional trauma for some physicians,1,2 particularly among trainees. Research is lacking that focuses on the emotional impact and coping techniques utilized by novice and experienced pediatricians after impactful pediatric patient deaths. Objectives: To define the salient features of an impactful pediatric patient death and physicians' grief and coping responses. As a secondary aim, we explored the cognitive and emotional training physicians described as helpful or would be helpful when coping after impactful patient deaths. Design: We conducted a prospective qualitative study using semistructured interviews and applied descriptive thematic content analysis to the transcribed interviews. Setting/Subjects: We enrolled pediatric intensive care unit trainees and attendings in a single United States institution over a six-month period from January 2021 to June 2021. Results: Both trainee and attending physicians were most impacted by acute or unexpected patient deaths. Trainees were particularly impacted by their first or early career patient deaths. Both groups found talking about the death of a patient the most helpful coping mechanism. Attending physicians coped with positive reframing, whereas novices more frequently utilized avoidance, numbing, and rumination. The importance of experienced physician's role modeling vulnerability and supporting trainee growth rather than "getting it right" were highlighted as trainee coping gaps. Conclusions: Novice physicians are particularly vulnerable to acute stress after the death of a patient and require additional coping resources and supports. Future projects should explore the impact of teaching emotion-focused coping techniques on trainee resiliency and coping after early career patient deaths.

Putting Prognosis First: Impact of an Intensive Care Unit Team Premeeting Curriculum.

Background: The paradigm of care has shifted in the pediatric intensive care unit (ICU) such that patients are frequently cared for by teams of specialists rather than the ICU attending physician solely managing care. An unintended consequence of care managed by multiple specialists is that families often receive conflicting messages from different team members, with little focus on disclosing prognosis. Objective: To address this gap, we developed and pilot-tested a team communication skills training (CST) program focused on the healthcare team premeeting in which roles, purpose, and prognosis are clarified before meeting with the family. Our aim was to assess whether the team CST program was associated with increased discussion of prognosis during the team premeeting. Methods: We conducted a single-center, observational pilot study to develop and test a team CST program using a before/after design. Pediatric ICU physicians and specialists from pediatric neurology and pediatric oncology who co-led family conferences in the pediatric ICU participated in a 1-day team CST program. Team premeetings were audio-recorded and transcribed. Results: We analyzed seven pre- and 10 post-CST program audio-recorded team premeetings, which each compromised a median of eight healthcare team members. Prognosis was more likely to be discussed in post-CST team premeetings (10/10 vs. 3/7; P = 0.0147). Agreement on prognosis was achieved more frequently in post-CST teams compared with pre-CST teams, although the percentage of agreement did not reach significance (9/10 vs. 3/7; P = 0.1007). Conclusions: A CST program with a structured approach to conducting a team premeeting was associated with an increased discussion of prognosis among team members before convening with the family in the pediatric ICU.

Longitudinal changes in respiratory and upper limb function in a pediatric type III spinal muscular atrophy cohort after loss of ambulation.

INTRODUCTION/AIMS: Spinal muscular atrophy (SMA) type III is a relatively mild form of SMA. Few studies have investigated the changes in both respiratory and upper limb function within this population after loss of ambulation. The aim of this study was to assess change in percentage of predicted forced vital capacity (FVC% predicted) and change in the Revised Upper Limb Module (RULM) score in these patients throughout a 24-month period after loss of ambulation. Effect of scoliosis and its surgical correction, disease duration since loss of ambulation, weight, and height were also investigated. METHODS: Retrospective analyses were performed on 24 nonambulant SMA III patients from data collected at two centers in the United Kingdom. RESULTS: The FVC% predicted score showed a significant progressive deterioration of 17% over the 24-month period. Respiratory deterioration correlated significantly with age, weight, disease duration since loss of ambulation, and spinal correctional surgery. Longitudinal RULM data were available for 16 patients; a significant deterioration was observed with a mean decrease in score of 3 over 24 months. Age correlated negatively with RULM score, as did height and time since loss of ambulation. A significant positive correlation between FVC% predicted and RULM was demonstrated. DISCUSSION: This study highlights how SMA type III patients have progressive deterioration of respiratory and upper limb function after loss of ambulation. Combining data from these assessments could provide insight into clinical progression, inform clinical trials, and provide assistance in managing disease progression expectations for patients.

Bone quality in fluoride-exposed populations: A novel application of the ultrasonic method.

BACKGROUND: Various studies, mostly with animals, have provided evidence of adverse impacts of fluoride (F-) on bone density, collagen and microstructure, yet its effects on overall bone quality (strength) has not been clearly or extensively characterized in human populations. OBJECTIVE: In this observational study, we assessed variation in an integrated measures of bone quality in a population exposed to wide-ranging F- levels (0.3 to 15.5 mg/L) in drinking water, using a novel application of non-ionizing ultrasonic method. METHOD: We collected 871 speed of sound (SOS) measurements from 341 subjects residing in 25 communities, aged 10-70 years (188 males and 153 females). All subjects received scans of the cortical radius and tibia, and adults over the age of 19 received an additional scan of the phalanx. Associations between F- in drinking water and 24-h urine samples, and SOS as a measure of bone quality, were evaluated in bivariate and multivariable regressions adjusting for age, sex, BMI, smoking, and toothpaste use. RESULTS: We found negative associations between F- exposure and bone quality at all three bones. Adult tibial SOS showed the strongest inverse association with F- exposure, which accounted for 20% of the variance in SOS measures (r = 0.45; n = 199; p < 0.0001). In adjusted analysis, a 1 mg/L increase in F- in drinking water was related to a reduction of 15.8 m/s (95% CI: -21.3 to -10.3), whereas a 1 mg/L increase in 24-h urinary F- (range: 0.04-39.5 mg/L) was linked to a reduction of 8.4 m/s (95% CI: -12.7, -4.12) of adult tibial SOS. Among adolescents, in contrast, weaker and non-significant inverse associations between F- exposure and SOS were found, while age, gender, and BMI were more significant predictors than in adults. CONCLUSIONS: These results are indicative of a fluoride-induced deterioration of bone quality in humans, likely reflecting a combination of factors related to SOS: net bone loss, abnormal mineralization and collagen formation, or altered microarchitecture. The portable and low-cost ultrasound technique appears potentially useful for assessment of bone quality, and should be tested in other locations and for other bone-related disorders, to assess the feasibility of its more extensive diagnostic use in hard-to-reach rural regions.

Unconventional Oil and Gas Energy Systems: An Unidentified Hotspot of Antimicrobial Resistance?

Biocides used in unconventional oil and gas (UOG) practices, such as hydraulic fracturing, control microbial growth. Unwanted microbial growth can cause gas souring, pipeline clogging, and microbial-induced corrosion of equipment and transportation pipes. However, optimizing biocide use has not been a priority. Moreover, biocide efficacy has been questioned because microbial surveys show an active microbial community in hydraulic fracturing produced and flowback water. Hydraulic fracturing produced and flowback water increases risks to surface aquifers and rivers/lakes near the UOG operations compared with conventional oil and gas operations. While some biocides and biocide degradation products have been highlighted as chemicals of concern because of their toxicity to humans and the environment, the selective antimicrobial pressure they cause has not been considered seriously. This perspective article aims to promote research to determine if antimicrobial pressure in these systems is cause for concern. UOG practices could potentially create antimicrobial resistance hotspots under-appreciated in the literature, practice, and regulation arena, hotspots that should not be ignored. The article is distinctive in discussing antimicrobial resistance risks associated with UOG biocides from a biological risk, not a chemical toxicology, perspective. We outline potential risks and highlight important knowledge gaps that need to be addressed to properly incorporate antimicrobial resistance emergence and selection into UOG environmental and health risk assessments.

The first pollution investigation of road sediment in Gary, Indiana: Anthropogenic metals and possible health implications for a socioeconomically disadvantaged area.

An investigation of road sediment in Gary, Indiana revealed high levels of various trace metals such as Zn, Mn, and Cr, often exceeding those of background reference concentrations as shown through geoaccumulation indices and contamination factors. The hazard index (HI) value for Mn in children was >1 (1.7), suggesting possible long-term non-carcinogenic health risk. Mn HI for children is even higher for the five samples closest to a US Steel facility, with an HI of 2.8. Through SEM-EDS analysis, the prevalence of small particulates (PM2.5 and PM2.5-10) containing potentially harmful elements such as Mn and Pb illustrate a health risk through direct inhalation or ingestion. The small nature of particulates in general may also pose an increased health risk for respiratory diseases such as asthma. Mn concentrations in the road sediment were particularly high, with 30 out of 32 samples exceeding 1800 ppm. Mn and V concentrations show a strong spatial trend of decreasing concentration away from a US Steel facility. These spatial trends along with correlation plots of the bulk chemistry suggest that industrial steel manufacturing, particularly US Steel in Gary, is a major contributing source of Mn and V. Fe and Cr show a moderate decrease in concentrations away from the US Steel facility, which suggests some sourcing from the steel facility when coupled with bulk chemistry plots. Zn and Cu do not show much evidence of sourcing from the US Steel facility, likely due to increased mixing from other sources. Further work constraining anthropogenic sources, the bioaccessible fraction of metals, and analysis of direct atmospheric particulates can help with remedial activity and risk assessment.