Patient-reported measures of tinnitus for individuals with neurofibromatosis type 2-related schwannomatosis: Recommendations for clinical trials.

BACKGROUND: Neurofibromatosis type 2-related schwannomatosis is a genetic disease characterized by the development of bilateral vestibular schwannomas, ependymomas, meningiomas, and cataracts. Mild to profound hearing loss and tinnitus are common symptoms reported by individuals with neurofibromatosis type 2. While tinnitus is known to have a significant and negative impact on the quality of life of individuals from the general population, the impact on individuals with neurofibromatosis type 2 is unknown. Consensus regarding the selection of suitable patient-reported outcome measures for assessment could advance further research into tinnitus in neurofibromatosis type 2 patients. The purpose of this work is to achieve a consensus recommendation by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration for patient-reported outcome measures used to evaluate quality of life in the domain of tinnitus for neurofibromatosis type 2 clinical trials. METHODS: The Response Evaluation in Neurofibromatosis and Schwannomatosis Patient-Reported Outcomes Communication Subgroup systematically evaluated patient-reported outcome measures of quality of life in the domain of tinnitus for individuals with neurofibromatosis type 2 using previously published Response Evaluation in Neurofibromatosis and Schwannomatosis rating procedures. Of the 19 identified patient-reported outcome measures, 3 measures were excluded because they were not validated as an outcome measure or could not have been used as a single outcome measure for a clinical trial. Sixteen published patient-reported outcome measures for the domain of tinnitus were scored and compared on their participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials. RESULTS: The Tinnitus Functional Index was identified as the most highly rated measure for the assessment of tinnitus in populations with neurofibromatosis type 2, due to strengths in the areas of item content, psychometric properties, feasibility, and available scores. DISCUSSION: Response Evaluation in Neurofibromatosis and Schwannomatosis currently recommends the Tinnitus Functional Index for the assessment of tinnitus in neurofibromatosis type 2 clinical trials.

Recommendations for assessing appearance concerns related to plexiform and cutaneous neurofibromas in neurofibromatosis 1 clinical trials.

BACKGROUND/AIMS: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. METHODS: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. RESULTS: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. CONCLUSION: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.

Drug Use and Human Milk: Legal and Child Welfare Considerations.

INTRODUCTION: Preventing new parents who use drugs from bonding with and bodyfeeding their babies undermines public health. Because U.S. culture treats substance use as a moral failing rather than a health concern, punitive responses to perinatal substance use continue to dominate. This is particularly true for families of color, who are more likely to be targeted by the family regulation system. These approaches fail to protect families, and cause their own, separate harm. This article will lay out existing evidence surrounding bodyfeeding. Then, it will debunk harmful mythologies about drug use and human milk, and compare the risks associated with using drugs while bodyfeeding to those inherent in family separation. Finally, it will make the case for harm-reduction approaches over criminal ones. OBJECTIVES: The health risks associated with family separation are only rarely weighed against those associated with drug exposure through human milk. Our objective for this paper is to contribute new ways of framing the importance of keeping families together at birth, even when perinatal substance use is detected. METHODS: This manuscript is not based upon clinical study or patient data, and exclusively references studies and research publications that have been approved by the appropriate ethics committee and which have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. RESULTS: Significant research data support the position that the risks associated with family separation are arguably greater than those associated with exposure to substance use in human milk. CONCLUSIONS FOR PRACTICE: Harm reduction approaches should be favored over criminal approaches when perinatal substance use is detected or confirmed.

The harms of family separation have already been well-documented by public health and social science researchers. The risks associated with substance use and human milk have also been the subject of significant academic research. However, the authors have not come across any articles that weigh the health risks associated with family separation against those associated with drug exposure through human milk. This paper contributes new ways of framing the importance of keeping families together at birth, even when perinatal substance use is detected.

Outcomes of Cannabis Use During Pregnancy Within the American Association of Birth Centers Perinatal Data Registry 2007-2020: Opportunities Within Midwifery-Led Care.

BACKGROUND: Healthcare providers require data on associations between perinatal cannabis use and birth outcomes. METHODS: This observational secondary analysis come from the largest perinatal data registry in the United States related to the midwifery-led birth center model care (American Association of Birth Centers Perinatal Data Registry; N = 19 286). Births are planned across all birth settings (home, birth center, hospital); care is provided by midwives and physicians. RESULTS: Population data show that both early and persistent self-reports of cannabis use were associated with higher rates of preterm birth, low-birth-weight, lower 1-minute Apgar score, gestational weight gain, and postpartum hemorrhage. Once controlled for medical and social risk factors using logistic regression, differences for childbearing people disappeared except that the persistent use group was less likely to experience "no intrapartum complications" (adjusted odds ratio [aOR] = 0.49; 95% confidence interval [CI], 0.32-0.76; P < .01), more likely to experience an indeterminate fetal heart rate in labor (aOR = 3.218; 95% CI, 2.23-4.65; P < .05), chorioamnionitis (aOR = 2.8; 95% CI, 1.58-5.0; P < .01), low-birth-weight (aOR = 1.8; 95% CI, 1.08-3.05; P < .01), and neonatal intensive care unit (NICU) admission (aOR = 2.4; 95% CI, 1.30-4.69; P < .05). CONCLUSIONS: Well-controlled data demonstrate that self-reports of persistent cannabis use through the third trimester are associated with an increased risk of low-birth-weight and NICU admission.

Mouse TU tagging: a chemical/genetic intersectional method for purifying cell type-specific nascent RNA.

Transcriptional profiling is a powerful approach for understanding development and disease. Current cell type-specific RNA purification methods have limitations, including cell dissociation trauma or inability to identify all RNA species. Here, we describe "mouse thiouracil (TU) tagging," a genetic and chemical intersectional method for covalent labeling and purification of cell type-specific RNA in vivo. Cre-induced expression of uracil phosphoribosyltransferase (UPRT) provides spatial specificity; injection of 4-thiouracil (4TU) provides temporal specificity. Only UPRT(+) cells exposed to 4TU produce thio-RNA, which is then purified for RNA sequencing (RNA-seq). This method can purify transcripts from spatially complex and rare (<5%) cells, such as Tie2:Cre(+) brain endothelia/microglia (76% validated by expression pattern), or temporally dynamic transcripts, such as those acutely induced by lipopolysaccharide (LPS) injection. Moreover, generating chimeric mice via UPRT(+) bone marrow transplants identifies immune versus niche spleen RNA. TU tagging provides a novel method for identifying actively transcribed genes in specific cells at specific times within intact mice.

Temporal Summation in Chronic Pelvic Pain.

OBJECTIVE: This study sought to characterize central sensitization further among women with chronic pelvic pain by identifying temporal summation using a cotton-tipped applicator test that can be used at the bedside. METHOD: A total of 36 women (18 with chronic pain and allodynia; 18 without pain) were recruited. Both groups were randomly assigned to receive 3 strokes of a benign stimulus on the abdomen at differing frequencies: 10, 30, or 100 seconds. Each group included 6 women. Pain was assessed using a rating scale of 1 to 10. Data were analyzed using the multivariate approach to repeated measures analysis of variance. RESULTS: The pattern of pain scores differed significantly between women with and without chronic pain (P = 0.002). Women with chronic pelvic pain and allodynia showed a statistically significant increase in pain with successive strokes of the cotton-tipped applicator (P = 0.012 for stroke 1 vs. 2, P = 0.026 for stroke 2 vs. 3, and P = 0.005 for stroke 1 vs. 3). CONCLUSION: Women with chronic pelvic pain and allodynia showed significant worsening of pain with successive strokes of a cotton-tipped applicator. This finding indicates that pain wind-up and central sensitization are present in women with chronic pelvic pain and allodynia. Identification of summation is further evidence of neuroplasticity, which is helpful in innovative therapies for chronic pelvic pain.

Caring for children with neurofibromatosis type 1.

This article discusses the variable physical manifestations of neurofibromatosis type 1 among children in terms of presentation, disease severity, and prognosis, and addresses appropriate nursing interventions and patient teaching.

Role of the Speech-Language Pathologist (SLP) in the Head and Neck Cancer Team.

While treatments for head and neck cancer are aimed at curing patients from disease, they can have significant short- and long-term negative impacts on speech and swallowing functions. Research demonstrates that early and frequent involvement of Speech-Language Pathologists (SLPs) is beneficial to these functions and overall quality of life for head and neck cancer patients. Strategies and tools to optimize communication and safe swallowing are presented in this chapter.

Health Outcomes of Medically and Economically Vulnerable Adults: A Comparison of Former Foster Youth and Nonfoster Youth.

Medically and economically vulnerable adults experience various challenges that can impact their health. Within this vulnerable population, there may be individuals who are even more vulnerable, those who have a history of involvement with the foster care system. The purpose of this study was to evaluate the difference of reported health-related problems between adults with previous foster care experience and other vulnerable adults. Physical, mental, and relational health was evaluated in this study. Practice and policy implications for mental health and medical professionals are discussed.

Critical reflection: a general practice support group experience.

The problem of medical practitioner burnout and loss of morale remains an ongoing challenge in the Australian health workforce. Collegiate recommendations are individualistic or personalised, or worse, punitive. Critical reflection in supervision is a long-accepted and key aspect of social work theory and practice. The use of critical reflection within a general practitioner support group is examined and key learnings from our findings over 3years are discussed. All participants reported the group enhanced individual and team workplace satisfaction, and wellbeing. This Practice and Innovation paper offers an example that could help improve current best practice in the pastoral support of medical practitioners.

Preliminary Study of a Caregiver-based Infant and Child Feeding and Swallowing Screening Tool.

OBJECTIVES: The Infant and Child Feeding Questionnaire (ICFQ) was created to facilitate early detection of feeding and swallowing problems. This is achieved by promoting effective communication between caregivers and health care providers resulting in referral for evaluation and treatment of feeding and swallowing problems by specialists. The purpose of this pilot study was to determine whether items from the ICFQ could be used to screen for differences between children with known feeding problems (FP) and without known feeding problems (NFP). METHODS: Caregivers of children ages 36 months or younger with FP and NFP were recruited to complete the ICFQ and demographic questions. T tests were completed to compare demographic characteristics of the research groups. Responses to ICFQ items were analyzed using receiver operating characteristic analysis and odds ratios to determine whether questionnaire items distinguished between study groups. RESULTS: Sixty-four caregivers of children with FP and 57 caregivers of NFP children were recruited. Three participants in the NFP group did not meet inclusion criteria and were excluded from analysis. A combination of 4 ICFQ questions distinguished between groups (receiver operating characteristic = 0.974). Significant odds ratios were also found for 9 feeding behaviors that distinguished between groups. CONCLUSIONS: A subset of items from the ICFQ showed promise for distinguishing FP from NFP groups. Future work will expand the regional representation of the participant samples and obtain equal representation of participants across all age-adjusted questionnaires to determine whether the same combination of ICFQ items continues to distinguish between FP and NFP groups.

Dissimilar Physiological and Perceptual Responses Between Sprint Interval Training and High-Intensity Interval Training.

High-intensity interval training (HIIT) and sprint interval training (SIT) elicit similar cardiovascular and metabolic adaptations vs. endurance training. No study, however, has investigated acute physiological changes during HIIT vs. SIT. This study compared acute changes in heart rate (HR), blood lactate concentration (BLa), oxygen uptake (VO2), affect, and rating of perceived exertion (RPE) during HIIT and SIT. Active adults (4 women and 8 men, age = 24.2 ± 6.2 years) initially performed a VO2max test to determine workload for both sessions on the cycle ergometer, whose order was randomized. Sprint interval training consisted of 8 bouts of 30 seconds of all-out cycling at 130% of maximum Watts (Wmax). High-intensity interval training consisted of eight 60-second bouts at 85% Wmax. Heart rate, VO2, BLa, affect, and RPE were continuously assessed throughout exercise. Repeated-measures analysis of variance revealed a significant difference between HIIT and SIT for VO2 (p < 0.001), HR (p < 0.001), RPE (p = 0.03), and BLa (p = 0.049). Conversely, there was no significant difference between regimens for affect (p = 0.12). Energy expenditure was significantly higher (p = 0.02) in HIIT (209.3 ± 40.3 kcal) vs. SIT (193.5 ± 39.6 kcal). During HIIT, subjects burned significantly more calories and reported lower perceived exertion than SIT. The higher VO2 and lower BLa in HIIT vs. SIT reflected dissimilar metabolic perturbation between regimens, which may elicit unique long-term adaptations. If an individual is seeking to burn slightly more calories, maintain a higher oxygen uptake, and perceive less exertion during exercise, HIIT is the recommended routine.

Assessing patient awareness of proper hand hygiene.

BACKGROUND: The authors hypothesized that patients may not understand the forms of effective hand hygiene employed in the hospital environment. LITERATURE REVIEW: Multiple studies demonstrate the importance of hand hygiene in reducing healthcare-associated infections (HAIs). Extensive research about how to improve compliance has been conducted. METHODOLOGY: Patients' perceptions of proper hand hygiene were evaluated when caregivers used soap and water, waterless hand cleaner, or a combination of these. RESULTS: No significant differences were observed, but many patients reported they did not notice whether their providers cleaned their hands. DISCUSSION: Educating patients and their caregivers about the protection afforded by proper, consistent hand hygiene practices is important. IMPLICATIONS FOR NURSING PRACTICE: Engaging patients to monitor healthcare workers may increase compliance, reduce the spread of infection, and lead to better overall patient outcomes. IMPLICATIONS FOR RESEARCH: This study revealed a need to investigate the effects of patient education on patient perceptions of hand hygiene. CONCLUSION: Results of this study appear to indicate a need to focus on patient education and the differences between soap and water versus alcohol-based hand sanitizers as part of proper hand hygiene. Researchers could be asking: "Why have patients not been engaged as members of the healthcare team who have the most to lose?"

A reciprocal translocation dissects roles of Pax6 alternative promoters and upstream regulatory elements in the development of pancreas, brain, and eye.

Pax6 encodes a transcription factor with key roles in the development of the pancreas, central nervous system, and eye. Gene expression is orchestrated by several alternative promoters and enhancer elements that are distributed over several hundred kilobases. Here, we describe a reciprocal translocation, called 1Gso, which disrupts the integrity of transcripts arising from the 5'-most promoter, P0, and separates downstream promoters from enhancers active in pancreas and eye. Despite this fact, 1Gso animals exhibit none of the dominant Pax6 phenotypes, and the translocation complements recessive brain and craniofacial phenotypes. However, 1Gso fails to complement Pax6 recessive effects in lacrimal gland, conjunctiva, lens, and pancreas. The 1Gso animals also express a corneal phenotype that is related to but distinct from that expressed by Pax6 null mutants, and an abnormal density and organization of retinal ganglion cell axons; these phenotypes may be related to a modest upregulation of Pax6 expression from downstream promoters that we observed during development. Our investigation maps the activities of Pax6 alternative promoters including a novel one in developing tissues, confirms the phenotypic consequences of upstream enhancer disruption, and limits the likely effects of the P0 transcript null mutation to recessive abnormalities in the pancreas and specific structures of the eye.

Distinct genetic control of autoimmune neuropathy and diabetes in the non-obese diabetic background.

The non-obese diabetic (NOD) mouse is susceptible to the development of autoimmune diabetes but also multiple other autoimmune diseases. Over twenty susceptibility loci linked to diabetes have been identified in NOD mice and progress has been made in the definition of candidate genes at many of these loci (termed Idd for insulin-dependent diabetes). The susceptibility to multiple autoimmune diseases in the NOD background is a unique opportunity to examine susceptibility genes that confer a general propensity for autoimmunity versus susceptibility genes that control individual autoimmune diseases. We previously showed that NOD mice deficient for the costimulatory molecule B7-2 (NOD-B7-2KO mice) were protected from diabetes but spontaneously developed an autoimmune peripheral neuropathy. Here, we took advantage of multiple NOD mouse strains congenic for Idd loci to test the role of these Idd loci the development of neuropathy and determine if B6 alleles at Idd loci that are protective for diabetes will also be for neuropathy. Thus, we generated NOD-B7-2KO strains congenic at Idd loci and examined the development of neuritis and clinical neuropathy. We found that the NOD-H-2(g7) MHC region is necessary for development of neuropathy in NOD-B7-2KO mice. In contrast, other Idd loci that significantly protect from diabetes did not affect neuropathy when considered individually. However, we found potent genetic interactions of some Idd loci that provided almost complete protection from neuritis and clinical neuropathy. In addition, defective immunoregulation by Tregs could supersede protection by some, but not other, Idd loci in a tissue-specific manner in a model where neuropathy and diabetes occurred concomitantly. Thus, our study helps identify Idd loci that control tissue-specific disease or confer general susceptibility to autoimmunity, and brings insight to the Treg-dependence of autoimmune processes influenced by given Idd region in the NOD background.

The preventable burden of mortality from unsafe abortion among female sex workers: a Community Knowledge Approach survey among peer networks in eight countries.

Previous studies have found high levels of unintended pregnancy among female sex workers (FSW), but less attention has been paid to their abortion practices and outcomes. This study is the first to investigate abortion-related mortality among FSW across eight countries: Angola, Brazil, Democratic Republic of Congo (DRC), India, Indonesia, Kenya, Nigeria, and South Africa. The Community Knowledge Approach (CKA) was used to survey a convenience sample of FSW (n = 1280). Participants reported on the deaths of peer FSW in their social networks during group meetings convened by non-governmental organisations (n = 165 groups, conducted across 24 cities in 2019). Details on any peer FSW deaths in the preceding five years were recorded. The circumstances of abortion-related deaths are reported here. Of the 1320 maternal deaths reported, 750 (56.8%) were due to unsafe abortion. The number of abortion-related deaths reported was highest in DRC (304 deaths reported by 270 participants), Kenya (188 deaths reported by 175 participants), and Nigeria (216 deaths reported by 312 participants). Among the abortion-related deaths, mean gestational age was 4.6 months and 75% occurred outside hospital. Unsafe abortion methods varied by country, but consumption of traditional or unknown medicines was most common (37.9% and 29.9%, respectively). The 750 abortion-related deaths led to 1207 children being left motherless. The CKA successfully recorded a stigmatised practice among a marginalised population, identifying very high levels of abortion-related mortality. Urgent action is now needed to deliver comprehensive sexual and reproductive healthcare to this vulnerable population, including contraption, safe abortion, and post-abortion care.

Causes of mortality among female sex workers: Results of a multi-country study.

Background: The vast majority of studies on female sex workers (FSW) focus on causes of morbidity while data on causes of mortality are scarce. In low- and middle-income countries, where civil registry and vital statistics data are often incomplete and FSW may not be identified as such in official registries, identifying causes of mortality among FSW has proven challenging. Methods: As part of a larger investigation on the maternal health of FSW, the current study used the Community Knowledge Approach (CKA) to identify causes of mortality among FSW in LMIC across three global regions in 2019. The CKA, validated to identify maternal, neonatal, and jaundice-associated deaths among women living in a community, was employed to identify deaths of any cause among communities of FSW. Study participants, recruited by in-country partner non-governmental organizations (NGOs) working with local FSW, provided detailed information about FSW deaths in their communities. Findings: 1280 FSW participated in 165 group meetings through which 2112 FSW deaths were identified. Of these reported deaths, 57·9% occurred in 2019 and 57·2% were among women aged 20-29. Causes of death included abortion (35·5%), other maternal causes (16·6%), suicide (13·6%), murder (12·5%), unclassified causes (11·6%), HIV/AIDS (7·9%), and accidents (3·2%). A total of 3659 children lost their mothers. Interpretation: Maternal death comprised the leading cause of FSW mortality in our sample. This methodology can be used by local governments and NGOs to identify unrecognized patterns and clusters of FSW deaths in near-real time and urgently steer targeted preventative strategies. Funding: New Venture Fund.

Motoring around the Golgi.

The Golgi apparatus is a dynamic organelle through which nascent secretory and transmembrane proteins are transported, post-translationally modified and finally packaged into carrier vesicles for transport along the cytoskeleton to a variety of destinations. In the past decade, studies have shown that a number of 'molecular motors' are involved in maintaining the proper structure and function of the Golgi apparatus. Here, we review just some of the many functions performed by these mechanochemical enzymes - dyneins, kinesins, myosins and dynamin - in relation to the Golgi apparatus.