Therapeutic drug monitoring of osimertinib in EGFR mutant non-small cell lung cancer by dried blood spot and plasma collection: A pilot study.

AIMS: Therapeutic drug monitoring (TDM) has led to significant improvements in individualized medical care, although its implementation in oncology has been limited to date. Tyrosine kinase inhibitors (TKIs) are a group of therapies for which TDM has been suggested. Osimertinib is one such therapy used in the treatment of epidermal growth factor receptor (EGFR) mutation-driven lung cancer. Herein, we describe a prospective pilot study involving 21 patients on osimertinib primarily as a preliminary evaluation of drug levels in a real-world setting. METHODS: Concentrations of the drug and its primary metabolites were measured with a validated liquid chromatography-mass spectrometry (LC-MS) assay across serial timepoints. As part of this study, inter-individual variability by dose and ethnicity as well as intra-individual variability across timepoints are explored. Furthermore, we attempted to validate dried blood spot (DBS)-based quantitation as an accurate alternative to plasma quantitation. RESULTS: Successful quantitation of osimertinib and primary metabolites was achieved for our subjects. Compound plasma levels were highly correlated to DBS levels. There was no significant difference in concentrations with ethnicity or dosing or intra-individual variability across timepoints. CONCLUSIONS: As such, we demonstrate that TDM for osimertinib is practical for future trials. We also validated the use of DBS as an alternative to conventional quantitation for exploration of TDM for osimertinib in larger trials and for other targeted therapies.

Characterizing the Validity of Using VASES to Derive DIGEST-FEES Grades.

INTRODUCTION: Visual Analysis of Swallowing Efficiency and Safety (VASES) and Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing (DIGEST-FEES) are two complimentary methods for assessing swallowing during FEES. Whereas VASES is intended to facilitate trial level ratings of pharyngeal residue, penetration, and aspiration, DIGEST-FEES is intended to facilitate protocol level impairment grades of swallowing safety and efficiency. The aim of this study was to assess the validity of using VASES to derive DIGEST-FEES impairment grades. METHODS: DIGEST-FEES grades were blindly analyzed from 50 FEES - first using the original DIGEST-FEES grading method (n = 50) and then again using a VASES-derived DIGEST-FEES grading method (n = 50). Weighted Kappa (κw), and absolute agreement (%) were used to assess the relationship between the original DIGEST-FEES grades and VASES-derived DIGEST-FEES grades. Spearman's correlations assessed the relationship between VASES-derived DIGEST-FEES grades with measures of construct validity. RESULTS: Substantial agreement (κw = 0.76 - 0.83) was observed between the original and VASES-derived grading methods, with 60-62% of all DIGEST-FEES grades matching exactly, and 92-100% of DIGEST-FEES grades within one grade of each other. Furthermore, the strength of the relationships between VASES-derived DIGEST-FEES grades and measures of construct validity (r = 0.34-0.78) were similar to the strength of the relationships between original DIGEST-FEES grades and the same measures of construct validity (r = 0.34-0.83). DISCUSSION/CONCLUSION: Findings from this study demonstrate substantial agreement between original and VASES-derived DIGEST-FEES grades. Using VASES to derive DIGEST-FEES also appears to maintain the same level of construct validity established with the original DIGEST-FEES. Therefore, clinicians and researchers may consider using VASES to increase the transparency and standardization of DIGEST-FEES ratings. Future research should seek to replicate these findings and to explore the simultaneous use of VASES and DIGEST-FEES in a greater sampling of raters and across other patient populations.

Reviews for multimorbidity risk in people with inflammatory conditions: a qualitative study.

BACKGROUND: People with inflammatory rheumatological conditions (IRCs) are at high risk of developing other conditions including cardiovascular disease and mood disorders. AIM: To explore perspectives of people with IRCs and healthcare practitioners (HCPs) on the content and delivery of a review consultation aimed at identification and management of multiple long-term conditions. DESIGN & SETTING: Semi-structured interviews and focus groups with people with IRCs and HCPs. METHOD: People with IRCs participated in individual semi-structured interviews by telephone or online platform. HCPs (including primary and secondary care clinicians) participated in online focus groups. Data were transcribed verbatim and analysed using inductive thematic analysis. RESULTS: 15 people with IRCs were interviewed; three focus groups with HCPs were conducted. Two main themes were identified: reflecting on the value of review consultations and what would a new review look like. Overall, people with IRCs and HCPs reflected that access to reviews is inequitable, leading to duplication of reviews and fragmentation in care. People with IRCs, at times, had difficulty conceptualising reviews, especially when discussing their future risk of conditions. People suggested that preparation before the healthcare review could align patient and HCP agendas as part of a flexible and person-centred discussion. CONCLUSION: Any review introduced for people with IRCs must move beyond a "tick-box" exercise. To gain maximum value from a review, preparation from both patient and HCP may be required alongside a person-centred approach whilst ensuring they are targeted at people most likely to benefit.

First-line chemoimmunotherapy and immunotherapy in patients with non-small cell lung cancer and brain metastases: a registry study.

Introduction: Brain metastases commonly occur in patients with non-small cell lung cancer (NSCLC). Standard first-line treatment for NSCLC, without an EGFR, ALK or ROS1 mutation, is either chemoimmunotherapy or anti-PD-1 monotherapy. Traditionally, patients with symptomatic or untreated brain metastases were excluded from the pivotal clinical trials that established first-line treatment recommendations. The intracranial effectiveness of these treatment protocols has only recently been elucidated in small-scale prospective trials. Methods: Patients with NSCLC and brain metastases, treated with first-line chemoimmunotherapy or anti-PD-1 monotherapy were selected from the Australian Registry and biObank of thoracic cancers (AURORA) clinical database covering seven institutions. The primary outcome was a composite time-to-event (TTE) outcome, including extracranial and intracranial progression, death, or need for local intracranial therapy, which served as a surrogate for disease progression. The secondary outcome included overall survival (OS), intracranial objective response rate (iORR) and objective response rate (ORR). Results: 116 patients were included. 63% received combination chemoimmunotherapy and 37% received anti-PD-1 monotherapy. 69% of patients received upfront local therapy either with surgery, radiotherapy or both. The median TTE was 7.1 months (95% CI 5 - 9) with extracranial progression being the most common progression event. Neither type of systemic therapy or upfront local therapy were predictive of TTE in a multivariate analysis. The median OS was 17 months (95% CI 13-27). Treatment with chemoimmunotherapy was predictive of longer OS in multivariate analysis (HR 0.35; 95% CI 0.14 - 0.86; p=0.01). The iORR was 46.6%. The iORR was higher in patients treated with chemoimmunotherapy compared to immunotherapy (58% versus 31%, p=0.01). The use of chemoimmunotherapy being predictive of iORR in a multivariate analysis (OR 2.88; 95% CI 1.68 - 9.98; p=0.04). Conclusion: The results of this study of real-world data demonstrate the promising intracranial efficacy of chemoimmunotherapy in the first-line setting, potentially surpassing that of immunotherapy alone. No demonstrable difference in survival or TTE was seen between receipt of upfront local therapy. Prospective studies are required to assist clinical decision making regarding optimal sequencing of local and systemic therapies.

Outcomes of minimally invasive isolated tricuspid valve repair and replacement through right mini-thoracotomy.

Objective: Isolated tricuspid valve surgery is uncommon and associated with high perioperative morbidity and mortality. We aimed to study the overall outcomes of patients who underwent minimally invasive right thoracotomy tricuspid valve surgery (Mini-TVS), consisting of either tricuspid valve repair (TVre) or replacement (TVR). Methods: We performed a retrospective analysis of all Mini-TVS procedures (2017-2022), through which we identified isolated tricuspid valve surgeries. We examined in-hospital outcomes, survival analysis over a 4-year period, and competing risk analysis for reoperative surgery. Results: Among a total of 51 patients, the average age was 60 ± 16 years, and 67% (n = 34) were female. Severe tricuspid regurgitation was present in all cases. Infective endocarditis was noted in 7.8% (n = 4), and 24% (n = 12) had preexisting pacemakers. Mini-TVS included TVre in 18 patients (35%) and TVR in 33 patients (65%). The in-hospital and 30-day mortality rates were 4% (n = 2) and 6% (n = 3), respectively. At 4 years, the overall TVS survival was 76% (confidence interval, 62-93%), with no significant difference between TVre and TVR (91% vs 69%, P = .16). At follow-up, 3 patients required repeat surgery for recurrent regurgitation after 2.6, 3.3, and 11 months, with a reoperation rate of 7.3% (confidence interval, 2.4-22%) at 2 years. Factors associated with worse overall survival included nonelective surgery, right ventricular dysfunction, serum creatinine >2 g/dL, and concomitant left-sided valve disease. Conclusions: A nonsternotomy minimally invasive approach is a feasible option for high-risk patients. Midterm outcomes were similar in repair or replacement. Patients with right ventricular dysfunction and left-sided disease had worse outcomes.

Brief Report: Real-World Toxicity and Survival of Combination Immunotherapy in Pleural Mesothelioma-RIOMeso.

BACKGROUND: Australia has one of the highest rates of asbestos-associated diseases. Mesothelioma remains an area of unmet need with a 5-year overall survival of 10%. First-line immunotherapy with ipilimumab and nivolumab is now a standard of care for unresectable pleural mesothelioma following the CheckMate 743 trial, with supportive data from the later line single-arm MAPS2 trial. RIOMeso evaluates survival and toxicity of this regimen in real-world practice. METHODS: Demographic and clinicopathologic data of Australian patients treated with ipilimumab and nivolumab in first- and subsequent-line settings for pleural mesothelioma were collected retrospectively. Survival was reported using the Kaplan-Meier method and compared between subgroups with the log-rank test. Toxicity was investigator assessed using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 119 patients were identified from 11 centers. The median age was 72 years, 83% were male, 92% had Eastern Cooperative Oncology Group less than or equal to 1, 50% were past or current smokers, and 78% had known asbestos exposure. In addition, 50% were epithelioid, 19% sarcomatoid, 14% biphasic, and 17% unavailable. Ipilimumab and nivolumab were used first line in 75% of patients. Median overall survival (mOS) was 14.5 months (95% confidence interval [CI]: 13.0-not reached [NR]) for the entire cohort. For patients treated first line, mOS was 14.5 months (95% CI: 12.5-NR) and in second- or later-line patients was 15.4 months (95% CI: 11.2-NR). There was no statistically significant difference in mOS for epithelioid patients compared with nonepithelioid (19.1 mo [95% CI: 15.4-NR] versus 13.0 mo [95% CI: 9.7-NR], respectively, p = 0.064). Furthermore, 24% of the patients had a Common Terminology Criteria for Adverse Events grade greater than or equal to 3 adverse events, including three treatment-related deaths. Colitis was the most frequent adverse event. CONCLUSIONS: Combination immunotherapy in real-world practice has poorer survival outcomes and seems more toxic compared with clinical trial data. This is the first detailed report of real-world survival and toxicity outcomes using ipilimumab and nivolumab treatment of pleural mesothelioma.

An Introduction to Faculty Diversity, Equity, and Inclusion for Excellence in Nurse Education: Literature Review.

BACKGROUND: The diversity of the world's population is increasing, along with the health inequities of underrepresented minority populations. To provide high-quality care to all patients, nurses require an understanding of diversity, equity, and inclusion (DEI) as well as how to implement best practices. Nurse educators are the ones to lead the way for DEI education for students. OBJECTIVE: This paper aims to describe the findings of a literature review that introduces DEI concepts for excellence in nurse education and their related benefits. Best practices for actions to address DEI in nursing education will be described. METHODS: After institutional review board approval, a literature search yielded 61 articles using 15 distinct keywords in 4 global, peer-reviewed literature databases. Melynk and Fineout-Overholt's (2023) Levels of Evidence guided the process of selecting 26 peer-reviewed articles and resources. RESULTS: Common themes for best practices in DEI were identified. These themes included recruiting underrepresented minority nursing faculty, incorporating DEI into an institution's mission statement, addressing DEI topics in curricula, providing leadership, having a DEI strategic plan, developing education, developing data-based interventions, instilling policy change, partnering in outreach, targeting impact on hiring committees, recognizing DEI work, and providing mentorship. CONCLUSIONS: In summary, this literature review provides several strategies to address DEI for nurse educators. Committing to DEI efforts and improving diversity in the nurse educator workforce are integral steps in improving the quality and inclusivity of nursing education and ultimately improving the health of our communities.

Impact of Transfer of Maternal Care for Fetal Anomalies on Maternal Depression and Anxiety Screening: A Prospective Cohort at a Tertiary Care Center.

INTRODUCTION: Perinatal depression and anxiety are major causes of maternal morbidity, and are more common in high-risk pregnancies compared to low-risk pregnancies. This study used validated screening tools to assess the prevalence of depression and anxiety symptoms in pregnant patients who transferred their obstetric care to a specialized fetal center for fetal anomaly. METHODS: This is a prospective cohort of patients with a fetal anomaly prompting transfer of obstetric care to Texas Children's Hospital Fetal Center between January 2021 and February 2022. The primary outcome was a self-assessed Edinburgh Postnatal Depression Scale score of 13 or higher, either antepartum or postpartum ("ever-positive EPDS"). Secondary outcomes included self-assessed Perinatal Anxiety Screening Scale (PASS) scores of 21 or higher ("ever-positive PASS"), obstetric outcomes, and neonatal outcomes. A frequentist analysis was performed. RESULTS: Of 149 women who transferred to Texas Children's Hospital during the study period, 94 enrolled in this study. Twenty-six percent of women had an ever-positive EPDS; 20% of patients had an ever-positive PASS. Patients were more likely to have an ever-positive EPDS if they were single (46% compared to 20%, p = 0.025). Women who had an ever-positive EPDS were more likely to be referred to psychiatry (46% compared to 14%, p = 0.004) and psychotherapy (29% compared to 1%, p < 0.001). Surprisingly, patients were more likely to have an ever-positive PASS if they reported good social support (p = 0.03). Antepartum EPDS and PASS scores had no relationship with postpartum EPDS scores. CONCLUSION: Women who transfer care to a tertiary setting have positive EPDS scores at double the rate of the general population, but tend to experience this either antepartum or postpartum (not both). Fetal centers should be prepared to screen for mental health symptoms before and after delivery and provide appropriate referral or treatment.

Dextromethorphan/quinidine for the treatment of bulbar impairment in amyotrophic lateral sclerosis.

OBJECTIVE: No efficacious treatments exist to improve or prolong bulbar functions of speech and swallowing in persons with amyotrophic lateral sclerosis (pALS). This study evaluated the short-term impact of dextromethorphan/quinidine (DMQ) treatment on speech and swallowing function in pALS. METHODS: This was a cohort trial conducted between August 2019 to August 2021 in pALS with a confirmed diagnosis of probable-definite ALS (El-Escorial Criteria-revisited) and bulbar impairment (ALS Functional Rating Scale score ≤ 10 and speaking rate ≤ 140 words per minute) who were DMQ naïve. Efficacy of DMQ was assessed via pre-post change in the ALS Functional Rating Scale-Revised bulbar subscale and validated speech and swallowing outcomes. Paired t-tests, Fisher's exact, and χ2 tests were conducted with alpha at 0.05. RESULTS: Twenty-eight pALS enrolled, and 24 participants completed the 28-day trial of DMQ. A significant increase in ALSFRS-R bulbar subscale score pre- (7.47 ± 1.98) to post- (8.39 ± 1.79) treatment was observed (mean difference: 0.92, 95% CI: 0.46-1.36, p < 0.001). Functional swallowing outcomes improved, with a reduction in unsafe (75% vs. 44%, p = 0.003) and inefficient swallowing (67% vs. 58%, p = 0.002); the relative speech event duration in a standard reading passage increased, indicating a greater duration of uninterrupted speech (mean difference: 0.33 s, 95% CI: 0.02-0.65, p = 0.035). No differences in diadochokinetic rate or speech intelligibility were observed (p > 0.05). INTERPRETATION: Results of this study provide preliminary evidence that DMQ pharmacologic intervention may have the potential to improve or maintain bulbar function in pALS.

Sensitivity and specificity of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised to detect dysarthria in individuals with amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Given the widespread use of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) to measure disease progression in ALS and recent reports demonstrating its poor sensitivity, we aimed to determine the sensitivity and specificity of the ALSFRS-R bulbar subscale and speech item to detect validated clinical ratings of dysarthria in individuals with ALS. METHODS: Paired ALSFRS-R and validated Speech Intelligibility Test (SIT) data from individuals with ALS were analyzed. Trained raters completed duplicate, independent, and blinded ratings of audio recordings to obtain speech intelligibility (%) and speaking rate (words per minute, WPM). Binary dysarthria profiles were derived (dysarthria ≤96% intelligible and/or <150 WPM). Data were obtained using the Kruskal-Wallis test, receiver-operating characteristic (ROC) curve, area under the curve (AUC), sensitivity and specificity percentages, and positive/negative predictive values (PPV/NPV). RESULTS: A total of 250 paired SIT and ALSFRS-R data points were analyzed. Dysarthria was confirmed in 72.4% (n = 181). Dysarthric speakers demonstrated lower ALSFRS-R bulbar subscale (8.9 vs. 11.2) and speech item (2.7 vs. 3.7) scores (P < .0001). The ALSFRS-R bulbar subscale score had an AUC of 0.81 (95% confidence interval [CI] 0.75 to 0.86). A subscale score of ≤11 yielded a sensitivity of 86%, specificity of 57%, PPV of 84%, and NPV of 60% to correctly identify dysarthria status. The ALSFRS-R speech item score demonstrated an AUC of 0.81 to detect dysarthria (95% CI 0.76 to 0.85), with sensitivity of 79%, specificity of 75%, PPV of 89%, and NPV of 58% for a speech item cutpoint of ≤3. DISCUSSION: The ALSFRS-R bulbar and speech item subscale scores may be useful, inexpensive, and quick tools for monitoring dysarthria status in ALS.

Experiences of dysmenorrhea and its treatment among allistic and autistic menstruators: a thematic analysis.

BACKGROUND: Dysmenorrhea (i.e., period pain) is common and debilitating. Autistic people are known to experience pain differently, yet little is known about the menstrual pain experiences of autistic menstruators relative to non-autistic peers. This study aimed to explore the experience of period pain and treatment uptake for period pain among allistic and autistic populations. METHODS: This study used a qualitative design and opportunity sampling approach. Thirty-seven participants (of whom 17 were autistic) were interviewed via video-conferencing software using a semi-structured topic guide. Transcriptions of interviews were analysed using Braun and Clarke's Reflexive Thematic Analysis. Data were initially analysed together for common themes. Autistic menstruators' data was subsequently analysed separately to elucidate the unique experiences of this group. RESULTS: A total of six themes were constructed from the data. Initial analysis determined three themes related to experiences of period pain and treatment uptake in both allistic and autistic menstruators. Social perception of menstruation was discussed, highlighting the normalisation of pain, the taboo nature, and gendered experience of menstruation, contributing to untreated menstrual pain. Issues within menstrual healthcare were also shared, including experiences of ineffective treatment, dismissive interactions, and insufficient menstrual education. Impaired functionality was repeatedly highlighted, with menstruators detailing significant limitations to their usual functioning due to menstrual pain and ineffective treatment. Three further themes were constructed from separate analysis of data from autistic menstruators. Autistic menstruators discussed the impact of menstruation on their sensory experiences and needs, with many identifying overstimulation during menstruation. Social exclusion was discussed as a factor contributing to the experience of menstrual pain and poor treatment uptake. The final theme identified pain communication differences between autistic and allistic menstruators resulting in reports of ineffective treatment and challenges in healthcare interactions. CONCLUSIONS: Communication differences, sensory aspects, and social factors contributed to the experience of period pain and treatment uptake for autistic menstruators. The perception of menstruation within society was highlighted by allistic and autistic menstruators as influential to their pain experience and engagement with treatment. Functionality was significantly impacted by pain for this sample. The study highlights societal and healthcare factors that could be improved to ensure accessibility of support and treatment for menstrual issues.

Maximum Phonation Time as a Surrogate Marker for Airway Clearance Physiologic Capacity and Pulmonary Function in Individuals With Amyotrophic Lateral Sclerosis.

PURPOSE: The increased use of telehealth practices has created a critical need for home-based surrogate markers for prognostic respiratory indicators of disease progression in persons with amyotrophic lateral sclerosis (pALS). Given that phonation relies on the respiratory subsystem of speech production, we aimed to examine the relationships between maximum phonation time (MPT), forced vital capacity, and peak cough flow and to determine the discriminant ability of MPT to detect forced vital capacity and peak cough flow impairments in pALS. METHOD: MPT, peak cough flow, forced vital capacity, and ALS Functional Rating Scale scores were obtained from 62 pALS (El-Escorial Revised) every 3 months as part of a longitudinal natural history study. Pearson's correlations, linear regressions, and receiver operator characteristic curve analyses with the area under the curve (AUC), sensitivity, specificity, and likelihood ratios were calculated. RESULTS: The mean age of pALS was 63.14 ± 10.95 years, 49% were female, and 43% had bulbar onset. MPT predicted forced vital capacity, F(1, 225) = 117.96, p < .0001, and peak cough flow, F(1, 217) = 98.79, p < .0001. A significant interaction was noted between MPT and ALS Functional Rating Scale-Revised respiratory subscore for forced vital capacity, F(1, 222) = 6.7, p = .010, and peak cough flow, F(1, 215) = 4.37, p = .034. The discriminant ability of MPT was excellent for peak cough flow (AUC = 0.88) and acceptable for forced vital capacity (AUC = 0.78). CONCLUSIONS: MPT is a simple clinical test that can be measured via telehealth and represents a potential surrogate marker for important respiratory and airway clearance indices. Further larger studies are required to validate these findings with remote data collection. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22186408.

Exploring the longer-term impact of the COVID-19 pandemic on physical and mental health of people with inflammatory rheumatic diseases: a cross-sectional survey.

OBJECTIVE: To assess the longer term impact of the COVID-19 pandemic on the self-reported physical and mental health of people with inflammatory rheumatic diseases (IRDs). METHODS: Two thousand twenty-four patients with IRDs were randomly selected from electronic health records. Survey invitations were sent (August 2021 coinciding with relaxation of UK COVID-19 restrictions) using SMS and postal approaches. Self-reported data included demographics, shielding status and physical (MSK-HQ) and mental health (PHQ8 and GAD7). RESULTS: Six hundred thirty-nine people completed the survey (mean (SD) age 64.5 (13.1) years, 384 (60%) female). Moderate/severe impact of the pandemic on physical and mental health was reported by 250 (41%) and 241 (39%) respectively. One hundred seventy-two (29%) reported moderate/severe depression (PHQ8 ≥ 10) and 135 (22%) moderate/severe anxiety (GAD7 ≥ 10). Females reported greater impacts of the pandemic on physical health (44% vs 34%), mental health (44% vs 34%), arthritis symptoms (49% vs 36%) and lifestyle factors (weight gain and reduced exercise and physical activity) than males. The physical and mental impacts were less in people with RA compared with other IRDs. Physical health impacts did not differ between age groups, but younger patients reported greater impacts on mental health. CONCLUSION: The COVID-19 pandemic has had a significant impact on the physical and mental health of people with IRDs. These effects were greatest in females. Recovery needs to address the negative impact of the pandemic on lifestyle factors to minimise the long-term impacts for people with IRDs. Key Points • The pandemic had a significant impact on long term physical and mental health in almost 40% of people with IRDs. • The impact of the pandemic was greater in women for physical health, mental health and arthritis symptoms. • Many people reported negative pandemic impacts on lifestyle factors including weight and physical activity.

Respiratory Strength Training in Amyotrophic Lateral Sclerosis: A Double-Blind, Randomized, Multicenter, Sham-Controlled Trial.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the short-term physiologic effect and one-year functional effect of a 12-week inspiratory and expiratory respiratory strength training (RST) program in individuals with amyotrophic lateral sclerosis (ALS). METHODS: A double-blinded, randomized, sham-controlled trial was conducted in 45 individuals with early-stage ALS. Participants were randomized into 12 weeks of active RST (30% load, n = 23) or sham RST (0% load, n = 22). An intent-to-treat analysis was conducted. Linear regression of pre-post change with group status and pretest scores as predictors was conducted. Primary outcomes included maximum expiratory and inspiratory pressure (MEP, MIP), and secondary outcomes were cough spirometry and forced vital capacity. Exploratory follow-up outcomes included one-year global and bulbar decline (ALS Functional Rating Scale-Revised [ALSFRS-R] total and bulbar subscale slope), oral intake status, and time to noninvasive ventilation (NIV). RESULTS: TheRST completion rate was 91% with no RST-related adverse events. A 12-week RST program led to increases in MEP (p = 0.004), but not MIP (p = 0.33). On average, MEP increased by 20.8 cm H2O after active RST (95% CI +7.6 to +33.9) and decreased by 1.0 cm H2O (95% CI -9.1 to +7.2) after sham RST. Mean MIP increased by 8.9 cm H2O (95% CI +1.5 to +16.3) and 4.8 cm H2O (95% CI -0.6 to +10.2) for the active and sham groups, respectively. Regarding secondary outcomes, RST led to significant increases in cough peak inspiratory flow (p = 0.02); however, it did not affect cough expiratory flow (p = 0.06) or FVC (p = 0.60). Regarding 12-month outcomes, a significant difference in the ALSFRS-R bulbar subscale slope was observed across treatment groups, with a more than two-fold faster rate of bulbar decline in the sham vs active RST groups observed (-0.29 vs -0.12 points/month, p = 0.02). Total ALSFRS-R slope, feeding status, and time to NIV did not differ across treatment groups (p > 0.05). DISCUSSION: RST was well tolerated and led to improvements in some, but not all, short and long-term outcomes. RST represents a proactive rehabilitative intervention that could increase physiologic capacity of specific breathing and airway clearance functions during the early stages of ALS. Further work is needed to determine optimal training intensity, resistance load specifications, and potential long-term functional outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that a mild-intensity respiratory strength training program improves maximum expiratory pressure, but not maximum inspiratory pressure, in patients with early-stage ALS.

Digital exclusion as a potential cause of inequalities in access to care: a survey in people with inflammatory rheumatic diseases.

Objectives: COVID-19 led to rapid uptake of digital health care. We sought to examine digital access, health and digital literacy, and impact on confidence and satisfaction with remote consultations in people with inflammatory rheumatic diseases (IRDs). Methods: People with IRDs (n = 2024) were identified from their electronic health record and invited to participate in a cross-sectional survey, using short message service (SMS) and postal approaches. Data were collected on demographics, self-reported diagnosis, access to and use of internet-enabled devices, health and digital literacy, together with confidence and satisfaction with remote consultations. Ethical approval was obtained (Ref 21/PR/0867). Results: Six hundred and thirty-nine (639) people completed the survey [mean (s.d.) age 64.5 (13.1) years, 384 (60.1%) female]. Two hundred and eighty-seven (44.9%) completed it online. One hundred and twenty-six (19.7%) people reported not having access to an internet-enabled device. Ninety-three (14.6%) reported never accessing the internet; this proportion was highest (23%) in people with RA. One hundred and seventeen (18%) reported limited health literacy. Even in those reporting internet use, digital literacy was only moderate. People with limited health or digital literacy or without internet access were less likely to report confidence or satisfaction with remote consultations. Conclusion: Limited health and digital literacy, lack of digital access and low reported internet use were common, especially in older people with RA. People with limited health literacy or limited digital access reported lower confidence and satisfaction with remote consultations. Digital implementation roll-out needs to take account of people requiring extra support to enable them to access care digitally or risks exacerbating health inequalities.

Profiles of Dysarthria and Dysphagia in Individuals With Amyotrophic Lateral Sclerosis.

PURPOSE: While dysarthria and dysphagia are known bulbar manifestations of amyotrophic lateral sclerosis (ALS), the relative prevalence of speech and swallowing impairments and whether these bulbar symptoms emerge at the same time point or progress at similar rates is not yet clear. We, therefore, sought to determine the relative prevalence of speech and swallowing impairments in a cohort of individuals with ALS and to determine the impact of disease duration, severity, and onset type on bulbar impairments. METHOD: Eighty-eight individuals with a confirmed diagnosis of ALS completed the ALS Functional Rating Scale-Revised (ALSFRS-R), underwent videofluoroscopy (VF), and completed the Sentence Intelligibility Test (SIT) during a single visit. Demographic variables including disease duration and onset type were also obtained from participants. Duplicate, independent, and blinded ratings were completed using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale and SIT to index dysphagia (DIGEST ≥ 1) and dysarthria (< 96% intelligible and/or < 150 words per minute) status. Descriptive statistics, Pearson chi-squared tests, independent-samples t tests, and odds ratios were performed. RESULTS: Dysphagia and dysarthria were instrumentally confirmed in 68% and 78% of individuals with ALS, respectively. Dysarthria and dysphagia were associated (p = .01), and bulbar impairment profile distributions in rank order included (a) dysphagia - dysarthria (59%, n = 52), (b) no dysphagia - dysarthria (19%, n = 17), (c) no dysphagia - no dysarthria (13%, n = 11), and (d) dysphagia - no dysarthria (9%, n = 8). Participants with dysphagia or dysarthria demonstrated 4.2 higher odds of exhibiting a bulbar impairment in the other domain than participants with normal speech and swallowing (95% CI [1.5, 12.2]). There were no differences in ALSFRS-R total scores or disease duration across bulbar impairment profiles (p > .05). ALSFRS-R bulbar subscale scores were significantly lower in individuals with dysphagia versus no dysphagia (8.4 vs. 10.4, p < .0001) and dysarthria versus no dysarthria (8.5 vs. 10.9, p < .0001). Dysphagia and onset type (p = .003) and dysarthria and onset type were associated (p < .0001). CONCLUSIONS: Over half of the individuals with ALS in this study demonstrated both dysphagia and dysarthria. Of those with only one bulbar impairment, speech was twice as likely to be the first bulbar symptom to degrade. Future studies are needed to confirm these findings and determine the longitudinal progression of bulbar impairments in this patient population.

YouTube as a Source of Patient Information Regarding Placenta Accreta Spectrum.

OBJECTIVE: As the awareness of the accompanying morbidity of placenta accreta spectrum (PAS) has increased over recent decades. We sought to analyze the precision and reliability of the currently available content regarding PAS on YouTube. STUDY DESIGN: A YouTube search was performed on June 17, 2019 by using the search terms "placenta accreta," "PAS," and "invasive placentation." Search results were sorted by relevance, and up to 200 videos per search term were systematically evaluated by four independent reviewers. A quality assessment checklist relating to aspects of PAS was developed with a Likert's scale from 0 to 12 points to quantify video content. Videos were classified as poor educational quality (grade 0 to ≤4), moderate quality (grade >4-8), and high quality (grade >8-12). RESULTS: Of the 318 videos identified, 99 videos met inclusion criteria. The majority of videos (61.6%) were produced by a professional source, that is, appearing to be from a hospital, university, or educational service. Of the remaining videos, 16.2% were classified as personal, that is, posted from personal YouTube accounts and depicting a personal or family member experience, and 22.2% were classified as other. The majority of the "other" category consisted of news segments and short clips from talk shows. Overall, 60.6% of videos were of poor educational quality, 32.3% were of moderate quality, and 7.1% were deemed high quality. All seven of the high-quality videos were produced by a professional source and intended for an audience of medical professionals. There were neither high-quality videos intended for the general public nor the likely affected and relevant patient population. CONCLUSION: This study suggests that the currently available videos on YouTube regarding PAS are poor educational sources for patients seeking information, and demonstrates a need for high-quality content videos produced by medical professionals specifically focused on meeting the needs of patient population. KEY POINTS: · Awareness of the accompanying morbidity of placenta accreta spectrum has increased over recent decades.. · YouTube videos are poor educational sources for patients seeking information regarding PAS.. · YouTube videos and all social media warrant improvements regarding patient's information..

Predictors of Peak Expiratory Cough Flow in Individuals with Amyotrophic Lateral Sclerosis.

Dystussia is prevalent in individuals with amyotrophic lateral sclerosis (ALS), leading to a diminished physiologic capacity to effectively defend the airway. We aimed to identify predictors of peak expiratory cough flow rate in individuals with ALS. One hundred and thirty-four individuals with a confirmed diagnosis of ALS (El-Escorial criteria revised) completed the ALS Functional Rating Scale-Revised (ALSFRS-R) and underwent pulmonary function and cough spirometry testing. Pearson's correlation coefficients and hierarchical multiple regression modeling were conducted to determine predictors of voluntary cough peak expiratory flow rate (p < 0.05). The full model including age, bulbar disease, cough spirometry metrics, and respiratory parameters had a marginal R2 = 0.635, F (7, 126) = 30.241, p < 0.0005, adjusted R2 = 0.61. Maximum expiratory pressure, compression phase, and vital capacity did not contribute and were therefore removed (p < 0.05). The most parsimonious predictive model included age, bulbar disease, peak inspiratory flow rate and duration, peak expiratory rise time, and inspiratory pressure generation with a marginal R2 = 0.543. Although expiratory pressure generation has historically served as the therapeutic target to improve dystussia in ALS, the current dataset highlighted that the inability to quickly and forcefully inspire during the inspiratory phase of voluntary cough places patients at a mechanical disadvantage to generate subsequent high-velocity expiratory airflow to clear the airway. Thus, therapeutic training programs that include both inspiratory and expiratory strength targets may optimize airway clearance capacity in this challenging patient population.