Peripheral Nerve Decline Impacts Lower Extremity Muscle Function in Older Adults

The prevalence of poor peripheral nerve function increases with age from approximately 8% at ages 40-49 to 35% after age 80 and likely contributes to declines in muscle strength, power, and mobility limitations. However, longitudinal evidence is lacking and the relationship between nerve function and muscle power has not been examined even at a cross-sectional level. This dissertation investigates the role of sensory and motor peripheral nerve function in muscle function decline and incident mobility limitation in older adults using data from two longitudinal cohort studies. Data from the Osteoporotic Fractures in Men Study (MrOS) show that poor motor and sensory nerve function are independently associated with poor muscle power and that light monofilament insensitivity is associated with greater decline in muscle power. Findings from the Health Aging and Body Composition (Health ABC) Study indicate that sensory and motor nerve function are predictive of subsequent strength and concurrent change in strength, although improvement in nerve function may not always lead to improvements in strength. We also found that sex modified the relationship between nerve function and strength, with motor and sensory nerve function being associated with strength in women and only sensory nerve function being associated with strength in men. Again using data from the Health ABC Study, we found that poor initial motor and sensory nerve function and sustained poor motor nerve function over seven years independently predicted incident mobility limitation. Understanding the role of neuromuscular parameters in the disablement process may help to identify multiple points of intervention. Our findings have important public health implications, suggesting a need for future work to examine early prevention of modifiable risk factors and secondary prevention to slow muscle function declines and prevent mobility limitation. Since our results persisted after adjustment for known risk factors for poor nerve function such as diabetes and vitamin B12 deficiency, novel risk factors should also be explored

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects

Purpose: Atezolizumab is a programmed death ligand 1 (PDL-1) blocking antibody that was approved for metastatic non-small cell lung cancer (NSCLC) in patients with disease progression. Various studies have been initiated to explore the effectiveness of atezolizumab among different patient cohorts and disease statuses, including as first-line therapy. The purpose of this paper is to identify and summarize the trials that use atezolizumab as a first-line agent in chemotherapy-naïve patients with NSCLC.Methods: A database search was performed on Pubmed, Embase, and Wiley Cochrane Library—Central Register of Controlled Trials to identify clinical trials using atezolizumab as first-line therapy in NSCLC. Additionally, ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) were searched to identify relevant clinical trials. Conference abstracts from the American Society of Clinical Oncology, the European Society for Medical Oncology, and the American Association for Cancer Research were hand-searched. Any trial in which atezolizumab was used as first-line therapy in chemotherapy-naive patients with NSCLC was included.Results: Fifteen studies were ultimately included, all of which are current and ongoing. Of the 15 studies, 5 have reported results. When given in the first-line setting, atezolizumab had higher rates of objective response, progression-free survival, and overall survival, compared to the second and third-line settings. Among the 15 studies, atezolizumab is used as monotherapy (n = 5), in combination with chemotherapy (n = 6), in combination with targeted therapy such as bevacizumab (n = 1), as neoadjuvant/adjuvant therapy (n = 3), in combination with stereotactic body radiation therapy (n = 1), and in combination with or following chemoradiation (n = 1).Conclusion: Available evidence shows promising safety and efficacy with the use of atezolizumab as first-line therapy in NSCLC. Atezolizumab is currently being studied in a variety of treatment settings. If clinical benefits are shown, atezolizumab may deem to be a useful first-line agent in NSCLC

Unexpectedly high concentrations of monoterpenes in a study of UK homes

The abundance of volatile organic compounds (VOCs) found in homes depends on many factors such as emissions, ventilation and the oxidative environment and these are evolving over time, reflecting changes in chemical use, behaviour and building design/materials. The concentrations of VOCs in 25 UK homes of varying ages, design and occupancy were quantified using continuous indoor air sampling over five days. Air was collected through low flow (1 mL min-1) constant flow restrictors into evacuated 6 L internally silica-treated canisters until the canisters reached atmospheric pressure. This was followed by thermal desorption-gas chromatography and high mass accuracy time-of-flight mass spectrometry (TD-GC-TOF/MS). A fully quantitative analysis was performed on the eight most abundant hydrocarbon-based VOCs found. Despite differences in building characteristics and occupant numbers 94% of the homes had d-limonene or α-pinene as the most abundant VOCs. The variability seen across the 25 homes in concentrations of monoterpenes indoors was considerably greater than that of species such as isoprene, benzene, toluene and xylenes. The variance in VOCs indoors appeared to be strongly influenced by occupant activities such as cleaning with 5-day average concentrations of d-limonene ranging from 18 μg m-3 to over 1400 μg m-3, a peak domestic value that is possibly the highest yet reported in the literature

Real-time COVID-19 hospital admissions forecasting with leading indicators and ensemble methods in England

Hospitalisations from COVID-19 with Omicron sub-lineages have put a sustained pressure on the English healthcare system. Understanding the expected healthcare demand enables more effective and timely planning from public health. We collect syndromic surveillance sources, which include online search data, NHS 111 telephonic and online triages. Incorporating this data we explore generalised additive models, generalised linear mixed-models, penalised generalised linear models and model ensemble methods to forecast over a two-week forecast horizon at an NHS Trust level. Furthermore, we showcase how model combinations improve forecast scoring through a mean ensemble, weighted ensemble, and ensemble by regression. Validated over multiple Omicron waves, at different spatial scales, we show that leading indicators can improve performance of forecasting models, particularly at epidemic changepoints. Using a variety of scoring rules, we show that ensemble approaches outperformed all individual models, providing higher performance at a 21-day window than the corresponding individual models at 14-days. We introduce a modelling structure used by public health officials in England in 2022 to inform NHS healthcare strategy and policy decision making. This paper explores the significance of ensemble methods to improve forecasting performance and how novel syndromic surveillance can be practically applied in epidemic forecasting

Variability of polycyclic aromatic hydrocarbons and their oxidative derivatives in wintertime Beijing, China

Ambient particulate matter (PM) can contain a mix of different toxic species derived from a wide variety of sources. This study quantifies the diurnal variation and nocturnal abundance of 16 polycyclic aromatic hydrocarbons (PAHs), 10 oxygenated PAHs (OPAHs) and 9 nitrated PAHs (NPAHs) in ambient PM in central Beijing during winter. Target compounds were identified and quantified using gas chromatography-time-of-flight mass spectrometry (GC-Q-ToF-MS). The total concentration of PAHs varied between 18 and 297 ngm-3 over 3 h daytime filter samples and from 23 to 165 ngm-3 in 15 h night-time samples. The total concentrations of PAHs over 24 h varied between 37 and 180 ngm-3 (mean: 97±43 ngm-3). The total daytime concentrations during high particulate loading conditions for PAHs, OPAHs and NPAHs were 224, 54 and 2.3 ngm-3, respectively. The most abundant PAHs were fluoranthene (33 ngm-3), chrysene (27 ngm-3), pyrene (27 ngm-3), benzo[a]pyrene (27 ngm-3), benzo[b]fluoranthene (25 ngm-3), benzo[a]anthracene (20 ngm-3) and phenanthrene (18 ngm-3). The most abundant OPAHs were 9,10-anthraquinone (18 ngm-3), 1,8-naphthalic anhydride (14 ngm-3) and 9-fluorenone (12 ngm-3), and the three most abundant NPAHs were 9-nitroanthracene (0.84 ngm-3), 3-nitrofluoranthene (0.78 ngm-3) and 3-nitrodibenzofuran (0.45 ngm-3). Σ PAHs and Σ OPAHs showed a strong positive correlation with the gas-phase abundance of NO, CO, SO2 and HONO, indicating that PAHs and OPAHs can be associated with both local and regional emissions. Diagnostic ratios suggested emissions from traffic road and coal combustion were the predominant sources of PAHs in Beijing and also revealed the main source of NPAHs to be secondary photochemical formation rather than primary emissions. PM2.5 and NPAHs showed a strong correlation with gas-phase HONO. 9- Nitroanthracene appeared to undergo a photodegradation during the daytime and showed a strong positive correlation with ambient HONO (R D 0:90, P <0:001). The lifetime excess lung cancer risk for those species that have available toxicological data (16 PAHs, 1 OPAH and 6 NPAHs) was calculated to be in the range 10-5 to 10-3 (risk per million people ranges from 26 to 2053 cases per year)

Clinical Educators’ Perceptions of Students Following a Simulation-Based Learning Program

Purpose: Clinical education is a key component of speech-language pathology university curriculum, whereby students have the opportunity to apply theoretical knowledge and practical skills learned in the classroom into a real workplace. However, more recently the availability of high quality, consistent clinical placements and learning experiences across the range of practice areas in the discipline is reducing. Therefore, alternative clinical learning opportunities that enable students to develop skills and competencies are being explored. Recently, replacing clinical time with a simulated learning program has been shown to achieve equivalent levels of clinical competency in speech pathology. However, it is unknown how simulation impacts on student learning in traditional clinical placements. Therefore, this research explored clinical educators’ perceptions of students undertaking clinical placements in their workplace immediately following a five-day simulation-based learning program related to the same area of practice. Method: Thirty-five clinical educators who supervised students in the workplace immediately after they completed the simulation program participated in semi-structured interviews. All interviews were transcribed verbatim and analyzed using qualitative methods described by Graneheim and Lundman (2004). Result: The analysis identified four key themes related to the impact of students in the workplace, simulation priming students for learning, the importance of the transition from simulation-based learning to the workplace, and the role of simulation in clinical education programs. Conclusion: The use of simulation to support student learning and develop clinical skills and competencies in adult speech pathology practice is supported by workplace clinical educators. However, results of this study suggest that the simulation program needs to be embedded within the curriculum and clinical education program to enhance transition between learning experiences and maximize benefits of learning experiences in real workplace contexts

Association of Cumulative Social Risk and Social Support With Receipt of Chemotherapy Among Patients With Advanced Colorectal Cancer

Importance: Approximately 38% of patients with advanced colorectal cancer do not receive chemotherapy. Objective: To determine whether cumulative social risk (ie, multiple co-occurring sociodemographic risk factors) is associated with lower receipt of chemotherapy among patients with advanced colorectal cancer and whether social support would moderate this association. Design, Setting, and Participants: This cross-sectional, population-based, mailed survey study was conducted from 2012 to 2014. Participants were recruited between 2011 and 2014 from all adults within 1 year after diagnosis of stage III colorectal cancer in the Detroit, Michigan, and State of Georgia Surveillance, Epidemiology, End-Results cancer registries. Patients were eligible if they were aged 18 years or older, had undergone surgery 4 or more months ago, did not have stage IV cancer, and resided in the registry catchment areas. Data analyses were conducted from March 2017 to April 2021. Main Outcomes and Measures: The primary outcome was receipt of chemotherapy. Cumulative social risk represented a sum of 8 risk factors with the potential to drain resources from participants\u27 cancer treatment (marital status, employment, annual income, health insurance, comorbidities, health literacy, adult caregiving, and perceived discrimination). Social support was operationalized as emotional support related to colorectal cancer diagnosis. Results: Surveys were mailed to 1909 eligible patients; 1301 completed the survey (response rate, 68%). A total of 1087 participants with complete data for key variables were included in the sample (503 women [46%]; mean [SD] age, 64 [13] years). Participants with 3 or more risk factors were less likely to receive chemotherapy than participants with 0 risk factors (3 factors, odds ratio [OR], 0.48 [95% CI, 0.26-0.87]; 4 factors, OR, 0.41 [95% CI, 0.21-0.78]; 5 factors, OR, 0.42 [95% CI, 0.20-0.87]; ≥6 factors, OR, 0.22 [95% CI, 0.09-0.55]). Participants with 2 or more support sources had higher odds of undergoing chemotherapy than those without social support (2 sources, OR, 3.05 [95% CI, 1.36-6.85]; 3 sources, OR, 3.24 [95% CI, 1.48-7.08]; 4 sources, OR, 3.69 [95% CI, 1.71-7.97]; 5 sources, OR, 4.40 [95% CI, 1.98-9.75]; ≥6 sources, OR 5.95 [95% CI, 2.58-13.74]). Within each social support level, participants were less likely to receive chemotherapy as cumulative social risk increased. Conclusions and Relevance: Cumulative social risk was associated with reduced receipt of chemotherapy. These associations were mitigated by social support. Assessing cumulative social risk may identify patients with colorectal cancer who are at higher risk for omitting chemotherapy who can be targeted for support programs to address social disadvantage and increase social support