Experiences of nurses and midwives with disabilities: A scoping review.

AIM: To identify the extent and type of evidence exploring the workplace experiences of nurses and midwives with disabilities. DESIGN: Scoping Review. DATA SOURCES: Four electronic databases were systematically searched in February 2022 to identify studies discussing the experiences of nurses and midwives with disabilities, published between 2012 and 2022. Google Scholar and Theses Global were also searched. REVIEW METHODS: All search results, irrespective of their format, were uploaded to Covidence to assist with the selection of evidence. Studies discussing the experiences of nurses and midwives with disabilities were included. Two reviewers conducted screening and data extraction independently, and a third reviewer resolved conflicts. RESULTS: Searches identified 130 studies. After screening for title and abstract, full-text review identified 23 studies for data extraction and analysis. Data were summarized and presented in tabular form under two categories (1) workplace experiences and (2) impact in the workplace. Results were presented in a descriptive, narrative form with accompanying tables. CONCLUSION: The nurse or midwife can be impacted significantly by disability. Currently, little is known about the workplace experiences of nurses and midwives with disabilities. Therefore, a better understanding of the experiences of the nurse and midwives with disabilities is important to increase diversity, equity, accessibility, and inclusion. IMPACT: Shortage of nurses and midwives worldwide highlights the need to understand why nurses and midwives with disabilities decide to leave the profession. Further research exploring the experiences of nurses or midwives with disabilities will help identify support requirements, develop frameworks for reasonable adjustment accommodations, and assist with future workforce planning. The EQUATOR guidelines for PRISMA have been met. No Patient or Public Contribution.

Validation of patient-reported vaso-occlusive crisis day as an endpoint in sickle cell disease studies.

Individuals with sickle cell disease (SCD) experience vaso-occlusive crises (VOC). Historically, VOC episodes have been assessed through medical utilization, thereby excluding events managed at home. In order to validate a daily patient-reported outcome for patients with SCD to accurately report their VOC status and experience of a pain crisis, a SCD Diary was included in Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS), a longitudinal, six-month, non-interventional study. The daily patient-completed diary included a description of SCD pain crisis, followed by questions on: pain crisis in the past 24 h (VOC Day question; respective response yes or no), worst pain, tiredness, and functioning. Thirty-five patients with SCD participated in ELIPSIS. Analyses were performed to validate the patient-reported VOC Day. Mean symptoms and functioning scores on the first or last VOC Day of a VOC Event were compared using t-tests with the mean of the three non-VOC Days before and after the event. Mean severity of symptoms and functioning scores on all VOC Days compared to all non-VOC Days were higher, with statistically significant mean differences between first/last VOC Days and respective three non-VOC Days (p's < .01). A subset of patients (n = 15) and caregivers (n = 9) were interviewed to evaluate their understanding of the SCD Diary questions. Nearly all confirmed that the pain crisis description accurately described the VOC experience, and participants expressed confidence differentiating SCD crisis pain from everyday pain. These results demonstrate patients can reliably report their experiences with VOC-related pain crises using the SCD Diary.

Validity of The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS): a daily activity criterion checklist for infants and toddlers.

BACKGROUND: The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) is a 50-item, criterion-specified questionnaire that assesses a child's adaptive skills in everyday context and can be used in high-risk follow-up settings to identify risk for adverse neurodevelopmental outcome. Our aim was to validate the WIDEA-FS by comparing a sample of typically developing children to children with special health needs and to compare results to the Capute Scales, which include domains of including both the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). METHODS: Six hundred and sixty children (typically developing and having special healthcare needs) aged 0-36 months completed the WIDEA-FS, the CAT, and the CLAMS assessments. RESULTS: Children with special health needs scored significantly lower on the WIDEA than those with typical development. WIDEA-FS subscales were significantly associated with the CAT (WIDEA-FS self-care 0.87, social cognition 0.89) and the CLAMS (WIDEA-FS communication 0.96, social cognition 0.92) tests. CONCLUSIONS: The WIDEA-FS has concurrent validity with the CAT and CLAMS and construct validity in that children with special health needs have significantly poorer performance on the WIDEA-FS than children with typical development. IMPACT: The WIDEA-FS demonstrated both construct validity and concurrent validity with the Capute Scales, including the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). This is the first study to validate the use of the WIDEA-FS in children with typical development and children with special healthcare needs. The WIDEA-FS is a quick and valid checklist that can be used to assess neurodevelopmental functioning during daily activities in typically developing children and those at risk for neurodevelopmental differences.

Comparative clinical outcomes between direct oral anticoagulants and warfarin among elderly patients with non-valvular atrial fibrillation in the CMS medicare population.

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) VS warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban-warfarin, 18,131 dabigatran-warfarin, and 55,359 rivaroxaban-warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59-0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73-0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72-1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57-0.67; NCO: HR: 0.64; 95% CI 0.60-0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71-0.89; NCO: HR: 0.84; 95% CI 0.76-0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02-1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99-1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin.

Reducing COPD readmissions through predictive modeling and incentive-based interventions.

This paper introduces a case study at a community hospital to develop a predictive model to quantify readmission risks for patients with chronic obstructive pulmonary disease (COPD), and use it to support decision making for appropriate incentive-based interventions. Data collected from the community hospital's database are analyzed to identify risk factors and a logistic regression model is developed to predict the readmission risk within 30 days post-discharge of an individual COPD patient. By targeting on the high-risk patients, we investigate the implementability of the incentive policy which encourages patients to take interventions and helps them to overcome the compliance barrier. Specifically, the conditions and scenarios are identified for either achieving the desired readmission rate while minimizing the total cost, or reaching the lowest readmission rate under incentive budget constraint. Currently, such models are under consideration for a pilot study at the community hospital.

An empirical tool for estimating the share of unmet need due to healthcare inefficiencies, suboptimal access, and lack of effective technologies.

BACKGROUND: Although there has been growing attention to the measurement of unmet need, which is the overall epidemiological burden of disease, current measures ignore the burden that could be eliminated from technological advances or more effective use of current technologies. METHODS: We developed a conceptual framework and empirical tool that separates unmet need from met need and subcategorizes the causes of unmet need into suboptimal access to and ineffective use of current technologies and lack of current technologies. Statistical models were used to model the relationship between health-related quality of life (HR-QOL) and treatment utilization using data from the National Health and Wellness Survey (NHWS). Predicted HR-QOL was combined with prevalence data from the Global Burden of Disease Study (GBD) to estimate met need and the causes of unmet need due to morbidity in the US and EU5 for five diseases: rheumatoid arthritis, breast cancer, Parkinson's disease, hepatitis C, and chronic obstructive pulmonary disease (COPD). RESULTS: HR-QOL was positively correlated with adherence to medication and patient-perceived quality and negatively correlated with financial barriers. Met need was substantial across all disease and regions, although significant unmet need remains. While the majority of unmet need was driven by lack of technologies rather than ineffective use of current technologies, there was considerable variation across diseases and regions. Overall unmet need was largest for COPD, which had the highest prevalence of all diseases in this study. CONCLUSION: We developed a methodology that can inform decisions about which diseases to invest in and whether those investments should focus on improving access to currently available technologies or inventing new technologies.

Benefits of quitting smoking on work productivity and activity impairment in the United States, the European Union and China.

BACKGROUND: Smoking has important health and economic consequences for individuals and society. This study expands the understanding of work-related burden associated with smoking and benefit of smoking cessation across the US, European Union (EU) and China using large-scale, representative survey methodology. METHODS: Data utilised the 2013 National Health and Wellness Survey in United States (US), EU5 (UK, France, Germany, Italy, and Spain) and China. Working-aged respondents 18-64 were used in the analyses (US N=58 500; EU5 N=50 417; China N=17 987) and were categorised into: current smokers, trying to quit, former smokers and never smokers. Generalised linear models controlling for demographics and health characteristics examined the relationship of smoking status with work productivity and activity impairment (WPAI-GH). The WPAI-GH measures were: absenteeism, presenteeism, overall work impairment, and activity impairment. Separately, current smokers were compared with those who quit 0-4, 5-10 and 11 or more years ago on WPAI-GH end-points. RESULTS: Current smokers reported greater absenteeism in the US and China and greater presenteeism, overall work impairment, and activity impairment than former and never smokers across the three regions. Those who quit even 0-4 years ago demonstrated lower absenteeism, presenteeism, and activity impairment in China and lower presenteeism, overall work impairment, and activity impairment in the US and EU5. CONCLUSIONS: Smoking was associated with significant work productivity loss in the US, EU5 and China. The results suggest that quitting benefits extend to work productivity rapidly after cessation, serving to further encourage and promote the implementation of workplace cessation programs.

Characteristics of first-time varenicline users - A cross-sectional study in Finnish quitters.

BACKGROUND: Varenicline is an efficacious medicine for smoking cessation (SC) but little is known about the characteristics of varenicline users. This study examined the characteristics of first-time (naïve) varenicline users in Finland and compared those who had previously used SC pharmacotherapy to those who were trying SC pharmacotherapy for the first time. METHODS: A cross-sectional survey was conducted in Finnish community pharmacies between February 2014 and January 2015. Pharmacy customers purchasing a varenicline starter package for the first time ever were asked to complete a questionnaire or to participate in a structured interview conducted by the pharmacist (identical questions). The questionnaire included questions about demographic characteristics, smoking habits, previous cessation attempts and factors associated with varenicline use. RESULTS: Altogether 98 people completed the survey. The majority were daily smokers (96%, n = 94), with a history of over 10 years of regular smoking (94%, n = 92), and a strong/very strong nicotine dependence (67%, n = 66). Half of the participants (54%, n = 53) were trying a SC pharmacotherapy for the first time. Demographic characteristics and smoking habits were similar between first-time and previous users of SC medications (p > 0.05). Health centers (42%, n = 41) and occupational health care clinics (37%, n = 36) were the most common sources of varenicline prescriptions. The majority of participants received the prescription for varenicline after mentioning their desire for quitting to a physician (70%, n = 69). CONCLUSIONS: Considering the relatively large proportion of SC naïve medicine users among new users of varenicline, smokers who have previously been reluctant to quit smoking, to use other pharmacological SC interventions, or perhaps unaware of these options may be interested in attempting cessation with varenicline. Most participants made the initiative to discuss their smoking with the physician, which led to varenicline prescribing. This suggests that physicians may not satisfactorily recognize their patients' nicotine dependence and desire to quit, and they should more actively support patients' smoking cessation.

The nature, characteristics and associations of care home staff stress and wellbeing: a national survey.

BACKGROUND: The majority of residents in care homes in the United Kingdom are living with dementia or significant memory problems. Caring in this setting can be difficult and stressful for care staff who work long hours, have little opportunity for training, are poorly paid and yet subject to high expectation. This may affect their mental and physical wellbeing, cause high rates of staff turnover and absenteeism, and affect the quality of care they provide. The main objective of this survey was to explore the nature, characteristics and associations of stress in care home staff. METHODS: Staff working in a stratified random sample of care homes within Wales completed measures covering: general health and wellbeing (SF-12); stress (Work Stress Inventory); job content (Karasek Job Content); approach to, and experience of, working with people living with dementia (Approaches to Dementia Questionnaire; and Experience of Working with Dementia Patients); and Productivity and Health Status (SPS-6). Multiple linear regressions explored the effects of home and staff characteristics on carers. RESULTS: 212 staff from 72 care homes completed questionnaires. Staff from nursing homes experienced more work stress than those from residential homes (difference 0.30; 95% confidence interval (CI) from 0.10 to 0.51; P < 0.01), and were more likely to report that their health reduced their ability to work (difference -4.77; CI -7.80 to -1.73; P < 0.01). Psychological demands on nurses were higher than on other staff (difference = 1.57; CI 0.03 to 3.10; P < 0.05). A positive approach to dementia was more evident in those trained in dementia care (difference 8.54; CI 2.31 to 14.76; P < 0.01), and in staff working in local authority homes than in the private sector (difference 7.75; CI 2.56 to 12.94; P < 0.01). CONCLUSIONS: Our study highlights the importance of dementia training in care homes, with a particular need in the private sector. An effective intervention to reduce stress in health and social care staff is required, especially in nursing and larger care homes, and for nursing staff. TRIAL REGISTRATION: ISRCTN registry: ISRCTN80487202. Registered 24 July 2013.

Alleviating staff stress in care homes for people with dementia: protocol for stepped-wedge cluster randomised trial to evaluate a web-based Mindfulness- Stress Reduction course.

BACKGROUND: There has been continuing change in the nature of care homes in the UK with 80 % of residents now living with some form of dementia or memory problem. Caring in this environment can be complex, challenging and stressful for staff; this can affect the quality of care provided to residents, lead to staff strain and burnout, and increase sickness, absence and turnover rates. It is therefore important to find interventions to increase the wellbeing of staff that will not only benefit staff themselves but also residents and care providers. Mindfulness training is known to be effective in treating a variety of physical and mental health conditions. METHODS AND DESIGN: The study uses mixed methods centred on a stepped-wedge cluster randomised trial. Thirty care homes in Wales are implementing a brief web-based mindfulness training course, starting in random sequence. Four to ten consenting staff from each facility undertake the course and complete validated questionnaires at baseline and after eight and 20 weeks. We shall also interview a stratified sample of ten trained staff and analyse the transcripts thematically. The primary outcome is stress; secondary outcomes include job satisfaction, attitudes towards residents and sickness absence rates. DISCUSSION: With increasing numbers of people living with dementia in care homes and causing stress in their carers, it is important to evaluate support strategies for staff. Mindfulness-based therapies may be of potential benefit and need detailed examination. TRIAL REGISTRATION: ISRCTN registry. ISRCTN80487202. Registered 24 July 2013.

The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene.

Lynch syndrome is characterized by mutations in one of four mismatch repair genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in PMS2 has previously been confined to Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method that permits detection of deletions of PMS2 Exons 12-15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3' deletions in 58 samples that were reported to be negative for PMS2 mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3' region of PMS2, including three previously reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15. Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through Alu-mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a PMS2 mutation based on immunohistochemical staining, for which mutations have not yet been identified, would benefit from testing using the new methodology.

Measurements of dune erosion processes during the RealDune/REFLEX experiments.

Nearshore hydro- and morphodynamic data were collected during a field experiment under calm conditions, moderate conditions, and storm conditions with dune erosion in the collision regime. The experiment was conducted on the Sand Engine near Kijkduin, the Netherlands, from October 18, 2021, to January 7, 2022. Two artificial unvegetated dunes were constructed just above the high water line to measure storm erosion and dune impacts from higher water levels and waves. During the experiment, three storms occurred that resulted in significant erosion of both dunes. The collected hydrodynamic data include pressure sensor and velocimeter data along two cross-shore transects. The collected morphodynamic data include bathymetry and topography surveys, optical backscatter sensor data in the inner surf zone, and a continuous cross-shore line-scanning lidar data set of the dune face. This comprehensive data set can be used to (1) study relevant nearshore hydrodynamic and morphodynamic processes that occur during calm conditions, moderate conditions, and storm conditions with dune erosion in the collision regime, and (2) validate existing dune erosion models.

Development of a Conceptual Model for the Patient Experience of Immunoglobulin A Nephropathy (IgAN): A Qualitative Literature Review.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is a kidney disorder that can lead to progressive kidney disease. Currently, there lacks a comprehensive overview of the symptoms and impacts experienced by those living with IgAN that would help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in clinical trials. The aim of this study was to develop a conceptual model of the adult and pediatric patient experience of IgAN, including disease signs and symptoms, treatment side effects, and impact on functioning and well-being. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and children diagnosed with IgAN. Data sources were identified through an electronic database search of journal articles (MEDLINE, Embase, PsycINFO; June 2021), hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from articles. Extracted data were qualitatively analyzed, aided by ATLAS.ti v7. Codes were applied to data; concepts (i.e., symptoms) were identified, named, and refined. A conceptual model was developed by grouping related concepts into domains. RESULTS: In total, five sources were identified for analysis: two journal articles, two online anthologies of patient stories, and one patient organization-sponsored "Voice of the Patient" meeting report. Conceptual model symptom domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight gain, sleep problems, urinary problems, and gastrointestinal problems. Impact domains included emotional/psychological well-being, physical functioning/activities of daily living, social functioning, work/school, and relationships. CONCLUSIONS: Secondary analysis of published qualitative literature permitted development of a novel conceptual model depicting the patient experience of IgAN; however, its depth is limited by a lack of available literature. Further qualitative research is recommended to refine and/or confirm the concepts and domains, determine any relationships between them, and explore the outcomes that are most meaningful to patients. The refined model will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future IgAN clinical trials.

Effectiveness of cognitive behavioural therapy (CBT) interventions for anxiety in patients with chronic obstructive pulmonary disease (COPD) undertaken by respiratory nurses: the COPD CBT CARE study: (ISRCTN55206395).

BACKGROUND: Anxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Serious implications can result from psychological difficulties in COPD including reduced survival, lower quality of life, and reduced physical and social functioning, increased use of health care resources and are associated with unhealthy behaviours such as smoking. Cognitive behavioural therapy (CBT) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression. Unfortunately access to trained CBT therapists is limited. The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population. In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study (Newcastle COPD CBT Care Study) is described. METHODS/DESIGN: This is a prospective open randomised controlled trial comparing CBT with self-help leaflets. The primary outcome measure is the Hospital Anxiety & Depression Scale (HADS) - anxiety subscale. Secondary outcome measures include disease specific quality of life COPD Assessment Tool (CAT), generic quality of life (EQ5D) and HADS-depression subscale. Patients will be followed up at three, six and 12 months following randomisation. DISCUSSION: This is the first randomised controlled trial to evaluate the use of cognitive behavioural therapy undertaken by respiratory nurses. Recruitment has commenced and should be complete by February 2014. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN55206395.

Development of a Conceptual Model for the Patient Experience of Focal Segmental Glomerulosclerosis (FSGS): A Qualitative Targeted Literature Review.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease and can progress to end stage kidney disease (ESKD). An overview of symptoms and impacts of the disease experienced will help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in FSGS clinical trials. This study aimed to develop a conceptual model (CM) of the adult and pediatric patient experience of FSGS including disease signs/symptoms, treatment side-effects, and impact on functioning and wellbeing. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and pediatric patients diagnosed with FSGS. Data sources were identified through an electronic database search of journal articles (Medline, Embase, PsycINFO; June 2021) and hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from the articles. Extracted data were qualitatively analyzed aided by ATLAS.ti v7. Codes were applied to data and concepts (symptoms/impacts) were identified, named, and refined. A CM was developed by grouping related concepts into domains. RESULTS: In total, 12 sources were identified for analysis: 6 journal articles and 6 series of patient testimonials. Salient sign/symptom/side-effect domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight changes, skin problems, respiratory problems, and sleep problems. Salient impact domains included emotional/psychological wellbeing, physical functioning/activities of daily living, social functioning, and work/school. CONCLUSION: Secondary analysis of published qualitative literature permitted development of a CM describing the adult and pediatric experience of FSGS. Concept elicitation interviews are recommended to refine the CM, confirm the salient/most bothersome concepts, and confirm the extent of impact on daily life. The refined CM will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future FSGS clinical trials.

Efficacy of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate for the prevention of heartworm disease in dogs.

Dirofilaria immitis, the mosquito-borne agent of dirofilariosis, a chronic and sometimes fatal cardiopulmonary canine disease, is endemic in most warm and temperate regions in the world. The efficacy of an oral endectoparasiticide product (test product or TP) combining moxidectin, afoxolaner, and pyrantel pamoate was evaluated for the prevention of heartworm disease in dogs, in two laboratory and one field studies. In each laboratory study, 20 D. immitis-naïve beagle dogs were experimentally infected with D. immitis. Ten control dogs were sham-treated, and ten dogs were administered the TP targeting the minimum effective dose, six times monthly and starting 30 days post infection. At necropsy seven months after inoculations, no heartworms were found in any of the TP treated dog, whereas 19 to 42 live heartworms were found in the control dogs. In each study, treatment efficacy was 100% and the difference between treated and untreated groups was highly significant (p < 0.0001). A field study was conducted through the full transmission season in several heartworm-endemic regions of the United States. One hundred and twenty client-owned dogs that were negative for D. immitis at enrollment were administered twelve monthly oral doses of the TP at label dose. Blood tests for D. immitis antigen and modified Knott's tests for microfilariae remained negative through the full duration of the study, demonstrating that all dogs were protected from heartworm infection during the full transmission season. These studies demonstrated that TP administered monthly for at least six doses is effective at preventing dirofilariosis.

Changes in health-related quality of life with smoking cessation treatment.

BACKGROUND: Cigarette smoking causes reduced health-related quality of life (QoL) and smoking abstinence improves health-related QoL. We assessed the effects of treatment for tobacco dependence on the health-related QoL in a 52-week randomized controlled trial of varenicline and bupropion sustained release (SR). METHODS: Subjects who smoked ≥10 cigarettes per day for the past year were randomly assigned to receive varenicline 1 mg twice daily (n = 696), bupropion SR 150 mg twice daily (n = 671) or placebo (n = 685) for 12 weeks and followed post-therapy for an additional 40 weeks. Health-related QoL was assessed using the Smoking Cessation Quality of Life questionnaire at baseline and Weeks 12, 24 and 52. RESULTS: Health transition (perceived health compared with baseline) and self-control were both significantly improved among subjects receiving varenicline and bupropion SR compared with placebo at Weeks 12, 24 and 52. Similarly, varenicline-treated subjects had significantly improved health transition and self-control compared with subjects who received bupropion SR at Weeks 12 and 24, and at Week 52 for health transition. A significant positive association existed between length of continuous abstinence and improved health transition, vitality, self-control, anxiety and overall mental profile. In most instances both a direct and an indirect effect (through continuous smoking abstinence) of each active treatment (vs. placebo) contributed to improved self-control and health transition. CONCLUSION: Treatment with varenicline and bupropion SR for smoking cessation resulted in improved self-control and health transition that was mediated in large part by continuous smoking abstinence.

Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer.

Mutational analysis of KRAS codons 12 and 13 is standard for patients with metastatic colorectal cancer since mutations in these codons predict lack of response to anti-EGFR therapies. However, even among patients whose tumors are wildtype for KRAS codons 12 and 13, only a subset respond to therapy. Since additional activating mutations downstream of EGFR may also play a role in treatment resistance, we sought to establish the frequency of these mutations. We evaluated 2121 colorectal tumors for mutations in codons 12 and 13 of the KRAS gene. A subset of these samples, comprised of 513 samples wildtype for KRAS codons 12 and 13, were tested for mutations in codons 61 and 146 of KRAS, codon 600 of BRAF, and codons 12, 13, and 61 of NRAS. Mutation status was determined by targeted pyrosequencing. Mutations in KRAS codon 12 or 13 were identified in 900/2121 (42.4%) samples. Of the 513 wildtype samples tested for additional mutations, 78 samples were mutant for BRAF, 19 for KRAS codon 61, 17 for KRAS codon 146, and 26 for NRAS. In total, 140/513 (27.3%) tumors wildtype for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes. While further study is needed to determine the full therapeutic implications of mutations in these codons, mutational testing of these codons may be useful for identifying a significant proportion of patients who may also be resistant to anti-EGFR therapies.

Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials.

BACKGROUND: This study aimed to identify fit-for-purpose clinical outcome assessments (COAs) to evaluate physical function, as well as social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia. Qualitative interviews lasting up to 90 min were conducted in the US with children/adolescents with achondroplasia and/or their caregivers. Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes. Cognitive debriefing methodology explored relevance and understanding of selected COAs. RESULTS: Interviews (N = 36) were conducted with caregivers of children age 0-2 years (n = 8) and 3-7 years (n = 7) and child/caregiver dyads with children age 8-11 years (n = 15) and 12-17 years (n = 6). Children/caregivers identified pain, short stature, impacts on physical functioning, and impacts on well-being (e.g. negative attention/comments) as key bothersome aspects of achondroplasia. Caregivers considered an increase in height (n = 9/14, 64%) and an improvement in limb proportion (n = 11/14, 71%) as successful treatment outcomes. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of Life in Short Stature Youth (QoLISSY-Brief) were cognitively debriefed. CHAQ items evaluating activities, reaching, and hygiene were most relevant. QoLISSY-Brief items evaluating reaching, height bother, being treated differently, and height preventing doing things others could were most relevant. The CHAQ and QoLISSY-Brief instructions, item wording, response scales/options and recall period were well understood by caregivers and adolescents age 12-17. Some children aged 8-11 had difficulty reading, understanding, or required caregiver input. Feedback informed minor amendments to the CHAQ and the addition of a 7-day recall period to the QoLISSY-Brief. These amendments were subsequently reviewed and confirmed in N = 12 interviews with caregivers of children age 0-11 (n = 9) and adolescents age 12-17 (n = 3). CONCLUSIONS: Achondroplasia impacts physical functioning and emotional/social well-being. An increase in height and improvement in limb proportion are considered to be important treatment outcomes, but children/adolescents and their caregivers expect that a successful treatment should also improve important functional outcomes such as reach. The CHAQ (adapted for achondroplasia) and QoLISSY-Brief are relevant and appropriate measures of physical function and emotional/social well-being for pediatric achondroplasia trials; patient-report is recommended for age 12-17 years and caregiver-report is recommended for age 0-11 years.