NEMA NU 2-2018 evaluation and image quality optimization of a new generation digital 32-cm axial field-of-view Omni Legend PET-CT using a genetic evolutionary algorithm.

A performance evaluation was conducted on the new General Electric (GE) digital Omni Legend PET-CT system with 32 cm extended field of view. The first commercially available clinical digital bismuth germanate system. The system does not use time of flight (ToF). Testing was performed in accordance with the NEMA NU2-2018 standard. A comparison was made between two other commercial GE scanners with extended fields of view; the Discovery MI - 6 ring (ToF enabled) and the Discovery IQ (non-ToF). A genetic evolutionary algorithm was developed to optimize image reconstruction parameters from image quality assessments. The Omni demonstrated average spatial resolutions at 1 cm radial offset as 3.9 mm FWHM. The total system sensitivity at the center was 44.36 cps/kBq. The peak NECR was measured as 501 kcps at 17.8 kBq ml-1with a 35.48% scatter fraction. The maximum count-rate error below NECR peak was 5.5%. Using standard iterative reconstructions, sphere contrast recovery coefficients were from 52.7 ± 3.2% (10 mm) to 92.5 ± 2.4% (37 mm). The PET-CT co-registration accuracy was 2.4 mm. In place of ToF, the Omni employs software corrections through a pre-trained neural network (PDL) (trained on non-ToF to ToF) that takes Bayesian penalized likelihood reconstruction (Q.Clear) images as input. The optimum parameters for image reconstruction, determined using the genetic algorithm were a Q.Clear parameter,ß, of 350 and a 'medium' PDL setting. Using standard iterative reconstructions, the Omni initially showed increased background variability compared to the Discovery MI. With optimized PDL reconstruction parameters selected using the genetic algorithm the performance of the Omni surpassed that of the Discovery MI on all NEMA tests. The genetic algorithm's demonstrated ability to enhance image quality in PET-CT imaging underscores the importance of algorithm driven optimization and underscores the requirement to validate its use in the clinical setting.

Experience and impact of stigma in people with chronic hepatitis B: a qualitative study in Asia, Europe, and the United States.

BACKGROUND: People with chronic hepatitis B (CHB) commonly experience social and self-stigma. This study sought to understand the impacts of CHB-related stigma and a functional cure on stigma. METHODS: Adults with CHB with a wide range of age and education were recruited from 5 countries and participated in 90-minute qualitative, semi-structured interviews to explore concepts related to CHB-associated stigma and its impact. Participants answered open-ended concept-elicitation questions regarding their experience of social and self-stigma, and the potential impact of reduced CHB-related stigma. RESULTS: Sixty-three participants aged 25 to 71 years (15 from the United States and 12 each from China, Germany, Italy, and Japan) reported emotional, lifestyle, and social impacts of living with CHB, including prejudice, marginalization, and negative relationship and work experiences. Self-stigma led to low self-esteem, concealment of CHB status, and social withdrawal. Most participants stated a functional cure for hepatitis B would reduce self-stigma. CONCLUSIONS: CHB-related social and self-stigma are widely prevalent and affect many aspects of life. A functional cure for hepatitis B may reduce social and self-stigma and substantially improve the health-related quality of life of people with CHB. Incorporating stigma into guidelines along with infectivity considerations may broaden the patient groups who should receive treatment.

Responding restoratively to elder harm: lessons from a pilot scheme in Aotearoa New Zealand.

The search for adequate ways to address elder harm and abuse has become increasingly evident in public discourse. There is a growing consensus that integrated, multi-disciplinary approaches are needed, especially because older victims are often hesitant to resort to legal interventions. This evaluation study aimed to assess the benefits and challenges of a pilot scheme in Aotearoa New Zealand employing restorative processes to respond to elder harm and to discuss implications for future practice. Thirty interviews were conducted with professionals, older persons and family members. Our findings show that restorative encounters, in particular circle processes, provided a safe environment to engage honestly with each other and for mutual understanding and trust to emerge. The collaborative relationship of key stakeholders was a notable strength of the pilot. However, the major challenge in using restorative practices was dealing adequately with long and complex histories of family conflicts.

Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage.

BACKGROUND & AIMS: The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts of sugar, such as sucrose. ISCs and TA cells are sensitive to dietary metabolites, but whether excess sugar affects their function directly is unknown. METHODS: Here, we used a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis) to show the direct effect of sugar on the transcriptional, metabolic, and regenerative functions of crypt ISCs and TA cells. RESULTS: We show that high-sugar conditions directly limit murine and human colonoid development, which is associated with a reduction in the expression of proliferative genes, adenosine triphosphate levels, and the accumulation of pyruvate. Treatment of colonoids with dichloroacetate, which forces pyruvate into the tricarboxylic acid cycle, restored their growth. In concert, dextran sodium sulfate treatment of mice fed a high-sugar diet led to massive irreparable damage that was independent of the colonic microbiota and its metabolites. Analyses on crypt cells from high-sucrose-fed mice showed a reduction in the expression of ISC genes, impeded proliferative potential, and increased glycolytic potential without a commensurate increase in aerobic respiration. CONCLUSIONS: Taken together, our results indicate that short-term, excess dietary sucrose can directly modulate intestinal crypt cell metabolism and inhibit ISC/TA cell regenerative proliferation. This knowledge may inform diets that better support the treatment of acute intestinal injury.

Psychometric validation and testing of the 10-item pediatric daily chest-related electronic patient reported outcome (ePRO) diary.

BACKGROUND AND OBJECTIVE: The chest-related electronic patient reported outcome (ePRO) diary was recently developed to assess chest-related symptoms experienced by pediatric and adolescent populations during upper respiratory tract infections (URTI). The objective of this research was the psychometric evaluation of the chest-related ePRO diary in pediatric, adolescent and adult participants. METHODS: This non-interventional, psychometric validation study involved participants (N = 195; n = 42 6-8 years; n = 47 9-11 years; n = 55 12-17 years, n = 51 18+ years) completing the chest-related ePRO diary twice daily for 10 days while experiencing an acute URTI. Preliminary item-level performance and dimensionality results, along with consideration of previous qualitative findings, were used to inform item reduction decisions, the structure of the measure and scoring algorithm development. Subsequent analyses on the finalized measure included assessments of reliability (internal consistency and test-retest reliability), construct validity (convergent validity and known groups validity) and ability to detect change. Comparisons of findings were made between the different age groups as part of the analyses to assess the psychometric properties of the chest-related ePRO diary and to characterize potential differences in the symptom experience of children, adolescents, and adults. RESULTS: The measure demonstrated strong quality of completion and showed relatively similar trajectories of symptom scores over time within different age subgroups and good item response distribution properties. Exploratory factor analysis supported a one-factor solution in the total population and within age subgroups, and test-retest reliability of the measure was strong (Intra-class correlation: 0.843-0.894 between Visit 1 and Day 1). The measure also demonstrated strong construct validity through high correlations with relevant items on the Child Cold Symptom Questionnaire (CCSQ), strong known groups validity (with statistically significant differences between severity groups) and was responsive to change over time with change groups defined based on change on global items. CONCLUSION: The findings demonstrate that the chest-related ePRO diary provides a valid, reliable, responsive measure of chest congestion symptoms experienced with the common cold in pediatric and adolescent populations, and that only minor differences are present in the disease trajectory when comparing adults to younger participants, supporting the use of the measure in interventional studies.

A qualitative study to examine meaningful change in physical function associated with weight-loss.

PURPOSE: This study explored perceptions of meaningful weight-loss and the level of change on two patient-reported outcome (PRO) measures, the 36-item Short Form Health Survey® [SF-36v2®] and Impact of Weight on Quality of Life Lite-Clinical Trials© [IWQOL-Lite-CT©], that individuals living with overweight or obesity consider to be meaningful and indicative of treatment success. METHODS: Thirty-three qualitative interviews were conducted in the US with adults living with overweight or obesity. Concept elicitation explored perceptions of minimally important/meaningful weight-loss using open-ended questions. Cognitive debriefing was used to understand thresholds for meaningful change on both measures. RESULTS: Most participants (n = 23/33) expected a 5% total body weight-loss to yield some benefit in physical functioning, while all participants expected a 10% weight-loss to provide a meaningful and noticeable improvement in their physical functioning. Participants indicated that an item-level 1-point score change on each measure would represent a noticeable improvement in physical functioning and indicate treatment success. CONCLUSIONS: Participants expected moderate weight-losses to be noticeable, with ≥ 10% weight-loss yielding the most consistent results. The findings suggested that both measures provide strong opportunity to demonstrate treatment benefit in relation to physical functioning as a small change on the response scale would represent a noticeable improvement in participants' daily lives.

Blueprint for harmonising unstandardised disease registries to allow federated data analysis: prepare for the future.

Real-world evidence from multinational disease registries is becoming increasingly important not only for confirming the results of randomised controlled trials, but also for identifying phenotypes, monitoring disease progression, predicting response to new drugs and early detection of rare side-effects. With new open-access technologies, it has become feasible to harmonise patient data from different disease registries and use it for data analysis without compromising privacy rules. Here, we provide a blueprint for how a clinical research collaboration can successfully use real-world data from existing disease registries to perform federated analyses. We describe how the European severe asthma clinical research collaboration SHARP (Severe Heterogeneous Asthma Research collaboration, Patient-centred) fulfilled the harmonisation process from nonstandardised clinical registry data to the Observational Medical Outcomes Partnership Common Data Model and built a strong network of collaborators from multiple disciplines and countries. The blueprint covers organisational, financial, conceptual, technical, analytical and research aspects, and discusses both the challenges and the lessons learned. All in all, setting up a federated data network is a complex process that requires thorough preparation, but above all, it is a worthwhile investment for all clinical research collaborations, especially in view of the emerging applications of artificial intelligence and federated learning.

A Qualitative Study to Develop and Evaluate the Content Validity of the Vitiligo Patient Priority Outcome (ViPPO) Measures.

INTRODUCTION: Vitiligo can be associated with a psychological burden, stigmatization and impaired quality of life. Tools to assess the impact of vitiligo exist; however, none were developed in line with the FDA's patient-reported outcome (PRO) Guidance for Industry. This study aimed to explore the content validity of two newly developed PRO measures to assess the impact of facial and total body vitiligo on how patients feel and function. METHODS: Draft PRO measures were developed from existing literature and input from PRO experts, a patient advocate and a clinical expert. Qualitative interviews were conducted with US participants living with vitiligo and international dermatologists with vitiligo expertise. Concept elicitation methodology explored the relevance of concepts in the draft PRO, while cognitive debriefing assessed conceptual relevance and understanding/interpretation. Items were iteratively amended/added throughout the interview study. RESULTS: The 60 participants included adults (n = 48, 63% female, 18-62 years old) and adolescents (n = 12, 67% female, 12-17 years old) with Fitzpatrick Skin Types I-VI. Expert dermatologists from the US (n = 8), EU (n = 4), India (n = 1) and Egypt (n = 1) participated. Concept elicitation was utilized to confirm the signs/symptoms of vitiligo and the associated impact on emotional/psychological wellbeing, social functioning, daily life and work/school. Conceptual saturation was achieved. Most participants reported impacts on their emotional/psychological wellbeing (n = 57, 95%), e.g. feeling self-conscious (n = 35, 58%). Participants reported impacts on social functioning (n = 53, 88%), e.g. vitiligo being noticed by others (n = 42, 70%). There was general consensus between participants and expert dermatologists. Cognitive debriefing confirmed that the items were well understood. Most items were conceptually relevant; feeling self-conscious and feeling frustrated were highly endorsed. Items were removed based on low conceptual relevance (feeling abandoned, skin roughness) and expected redundancy (four items), resulting in two measures with three proposed domain scores: Emotional/Psychological Wellbeing; Social Functioning; and Physical Sensation. No comprehension concerns were observed in relation to the 7-day recall period or the item response scale/options. Eight dermatologists reviewed the PRO measures, confirming comprehensiveness and relevance. CONCLUSION: The draft Vitiligo Patient Priority Outcomes (ViPPO) measures evaluate the impact of facial (ViPPO-F) and total body (ViPPO-T) vitiligo on emotional/psychological and social functioning. The ViPPO measures are well understood, comprehensive and content valid for adults and adolescents with vitiligo.

Meaningful Changes in What Matters to Individuals with Vitiligo: Content Validity and Meaningful Change Thresholds of the Vitiligo Area Scoring Index (VASI).

INTRODUCTION: This study explored patients' and dermatologists' priority outcomes for treatment to address, clinical outcome assessments (COA) for use in vitiligo clinical trials, and perceptions of within-patient meaningful change in facial and total body vitiligo. METHODS: Semistructured, individual, qualitative interviews were conducted with patients living with non-segmental vitiligo in the USA and with expert dermatologists in vitiligo. Concept elicitation discussions included open-ended questions to identify patient priority outcomes. Vitiligo COAs were reviewed by dermatologists. Tasks were completed by patients to explore their perceptions of meaningful changes in vitiligo outcomes; dermatologists' opinions were elicited. Data were analyzed using thematic methods; meaningful change tasks were descriptively summarized. RESULTS: Individuals with vitiligo (N = 60) included adults (n = 48, 63% female) and adolescents (n = 12, 67% female). All Fitzpatrick Skin Types were represented. Eight (13%) were first- or second-generation immigrants to the USA. Expert dermatologists (N = 14) participated from the USA (n = 8), EU (n = 4), India (n = 1), and Egypt (n = 1). All individuals with vitiligo reported experiencing skin depigmentation; an observable clinical sign of vitiligo. Most confirmed that lesion surface area (n = 59/60, 98%) and level of pigmentation (n = 53/60, 88%) were important to include in disease assessments. Following an explanation, participants (n = 49/60, 82%) felt that the Facial Vitiligo Area Scoring Index (F-VASI) measurement generally made sense and understood that doctors would use it to assess facial vitiligo. Most participants felt that a 75% (n = 47/59, 80%) or 9 0% improvement in their facial vitiligo would be indicative of treatment success (n = 55/59, 93%). In the context of evaluating a systemic oral treatment for vitiligo, dermatologists perceived a 75% improvement on the F-VASI as successful (n = 9/14, 64%). Regarding the Total VASI (T-VASI) score, n = 30 participants considered 33% improvement as treatment success; an additional n = 10 endorsed 50% improvement and a further n = 5 endorsed 75% improvement. Clinicians most frequently identified 50% (n = 6/14, 43%) or 75% (n = 4/14, 29%) improvement in T-VASI as successful. CONCLUSION: Repigmentation is a priority outcome for patients. The VASI was considered an appropriate tool to assess the extent of vitiligo. A minimum 75% improvement from baseline in the F-VASI and minimum 50% improvement from baseline in the T-VASI were identified as within-patient clinically meaningful thresholds.

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.

Development and content validity testing of patient-reported outcome (PRO) items to assess chest congestion associated with the common cold for use in children and adolescents.

BACKGROUND: This article describes qualitative interviews conducted with children (aged 6-11), adolescents (aged 12-17), and adults with the common cold as well as parents/caregivers of the 6-8-year-old children. The aim was to support the refinement and content validity testing of patient-reported outcome (PRO) items assessing chest congestion that could be used as pediatric clinical trial endpoints. Feasibility and acceptability of administering the PRO items electronically on a hand-held touch-screen device were also evaluated. The sample included children aged 6-8 years (n = 14), 9-11 years (n = 13), adolescents aged 12-17 years (n = 12), and adults (n = 10), all of who had current (n = 38) or recent (n = 11) cold. Both concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted with all of these participants, conducted over in two rounds. Ten parents/caregivers of participants aged 6-8 years were also interviewed (separately from their child) regarding how they thought their children would understand the items. The CE interviews explored the qualitative experience of having chest congestion and related symptoms of the common cold. Following their CE interview, participants completed draft items on an electronic patient-reported outcome (ePRO) device twice daily for 2-5 days prior to their CD interview. During the CD interview participants were asked about relevance, understanding and interpretation of the draft PRO items. Qualitative analysis of the interview data and descriptive analyses of the ePRO data were conducted following both rounds of interviews, with modifications to the items implemented following Round 1 and tested in Round 2. RESULTS: Eight symptoms were reported by children during concept elicitation. Findings from the child, adolescent, and adult/parent interviews supported revisions to the items and enabled the selection of the best performing items. The results provided evidence that the final items were well understood by participants and relevant to their experiences of chest congestion as part of a common cold. Findings also provide support for using the same items across age groups. CONCLUSIONS: The results of the CE and CD interviews provide evidence supporting the content validity of new PRO items assessing the experience of chest congestion symptoms associated with common cold experienced by children, adolescents, and adults.

Cost and clinical benefit of imaging surveillance after treatment for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

Recent UK guidelines recommend that surveillance imaging should not be offered to patients who have undergone treatment for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) unless clinically indicated. The aim of this study was to explore the evolving practice at a tertiary referral unit and quantify the direct economic costs (DEC) associated with post-treatment BIA-ALCL routine radiological surveillance prior to adoption of the guidelines. Eleven patients were treated for BIA-ALCL between 2015 and 2020. At a median follow-up of 38 months (IQR 12-47) there were no local or distant relapses. Two patients did not have any radiological surveillance and 1 had follow-up elsewhere. The remaining 8 patients had a combination of positron emission tomography/computed tomography (PET/CT) (n = 10), CT (n = 2), breast ultrasound (n = 6), mammogram (n = 4) and breast magnetic resonance imaging (MRI) (n = 1) as routine imaging follow-up not guided by clinical concerns. Total cost of imaging was £10,396 (€12,257) with a median cost of £1953 (€2304) per patient [IQR £526-2029 (€621-2394)]. This cost could have been saved based on current guidelines recommending no routine surveillance for asymptomatic patients.

Health practitioner experience of Health and Disability Commissioner investigations.

INTRODUCTION The New Zealand Health and Disability Commissioner (HDC) Act 1994 was designed to protect the rights of consumers and provide a fair, simple, speedy, and efficient resolution to complaints. No recent studies have been published about the health practitioner experience of HDC investigations following a patient complaint, and none that include nurses and midwives. AIM To use a restorative inquiry framework to understand the impacts and needs of health practitioners arising from an event that led to an investigation by the HDC during the last 10 years. METHODS A descriptive qualitative approach was used with data collected using semi-structured interviews with doctors, nurses, and midwives (n = 13). The data were analysed using thematic analysis. RESULTS Participants worked in primary care, aged care, and services provided by public hospitals. The emotional impacts arising from the event and investigation were profound, with long-lasting effects on participants' sense of self, reputation, and how, or if, they continued to practice. Participants indicated a need for support from colleagues and employers, a fair and relational investigation process, and a meaningful way of connecting to put things right. DISCUSSION A shift to a restorative approach whereby people involved in a complaint come together to speak truthfully about what happened and its impact on their lives, offers hope for a process that repairs relationships and improves health services. Restorative approaches clarify accountabilities and could lead to more satisfactory outcomes for all parties. This study contributes to emerging thinking about the use of restorative approaches in health-care contexts.

Whiskers as a novel tissue for tracking reproductive and stress-related hormones in North Pacific otariid pinnipeds.

Keratinized tissues, including whiskers, are ideal for acquiring a record of physiological parameters. Most tissues provide a snapshot of physiological status; however, whiskers may support longitudinal sampling for reproductive and stress-related hormones, if hormones are incorporated as whiskers grow and concentrations change with physiological state. Whiskers from female Steller sea lions (Eumetopias jubatus) and northern fur seals (Callorhinus ursinus) were serially sectioned and pulverized and steroid hormones were extracted. Standard methods were used to validate enzyme immunoassay kits for cortisol, progesterone, 17ß-estradiol and testosterone. All hormones were measurable in whisker segments from both species with progesterone concentrations showing cyclical patterns, which appear to signify previous pregnancies or luteal phases. Yearly progesterone concentrations were greater in years a pup was produced compared with years when no pup was observed. Free-ranging female Steller sea lions had reproductive rates between 0 and 1.0 (0.53 ± 0.33, n = 12) using a yearly progesterone concentration of 30 pg/mg or greater to classify a reproductive year as producing a pup and below 30 pg/mg as non-reproductive. Cortisol concentrations were greater near the root and rapidly declined, lacking any obvious patterns, throughout the rest of the whisker. Progesterone and testosterone concentrations were able to help determine sex of unknown individuals. Immunohistochemistry revealed that steroid hormones most likely do not leach out of whiskers based on the deposition patterns of progesterone and cortisol being present throughout the whisker length. Overall, measuring steroid hormones in whiskers can reveal individual reproductive histories over multiple years in sea lions and fur seals. Cyclical patterns of δ15N were useful for identifying periods of up to ~10 years of growth within whiskers, and measuring both stable isotopes and hormones may be useful for differentiating periods of active gestation from diapause and potentially track multi-year reproductive histories of female otariids.

Testing and Psychometric Validation of a Pediatric Instrument to Self-Assess Symptoms of the Common Cold.

OBJECTIVES: Given the lack of validated patient-reported outcomes (PRO) instruments assessing cold symptoms, a new pediatric PRO instrument was developed to assess multiple cold symptoms: the Child Cold Symptom Questionnaire (CCSQ). The objective of this research was to evaluate the measurement properties of the CCSQ. METHODS: This observational study involved daily completion of the self-report CCSQ by children aged 6-11 years in their home for 7 days. These data were used to develop a scoring algorithm and item-scale structure and evaluate the psychometric properties of the resulting scores. Analyses included evaluation of item and dimensionality performance (item response distributions and confirmatory factor analysis) and assessment of test-retest reliability in stable patients, construct validity (convergent and known groups validity), and preliminary responsiveness. Qualitative exit interviews in a subgroup of the children with colds and their parents were conducted. RESULTS: More than 90% of children had no missing data during the testing period, reflecting an excellent completion rate. For most items, responses were distributed across the options, with approximately normal distributions. Test-retest reliability was adequate, with intra-class correlation coefficients ranging from 0.63 to 0.83. A logical pattern of correlations with the validated Strep-PRO instrument provided evidence supporting convergent validity. Single- and multi-item symptom scores distinguished between children who differed in their cold severity based on global ratings, providing evidence of known groups validity. Preliminary evidence indicates the CCSQ is responsive to changes over time. CONCLUSIONS: The findings demonstrate that the CCSQ items and multi-item scores provide valid and reliable patient-reported measures of cold symptoms in children aged 6-11 years. They provide strong evidence supporting the validity of these items and multi-item scores for inclusion as endpoints in clinical trials to evaluate the efficacy of cold medicines.

Development and Content Validity Testing of Patient-Reported Outcome Items for Children to Self-Assess Symptoms of the Common Cold.

BACKGROUND AND OBJECTIVE: No pediatric patient-reported outcome instruments specific to the common cold are found in the literature. This study involved development and content validity testing of patient-reported outcome items (questions and response options) assessing cold symptoms in children aged 6-11 years. METHODS: Draft patient-reported outcome instructions, items, response scales, and recall periods were developed based on the literature and existing measures. Qualitative interviews were conducted with children (n = 39) who were currently (n = 31) or had recently (n = 8) experienced a cold and ten parents of a subset of children aged 6-8 years. The interviews were conducted over two rounds and included open-ended concept elicitation questioning, a free-drawing task, a card sorting task, and a task involving circling parts of the body, followed by cognitive debriefing of draft items. Thematic analysis of verbatim transcripts was performed to analyze the qualitative data. The findings were used to support revisions to the draft patient-reported outcome. RESULTS: Ten symptom concepts were reported by the children during concept elicitation. The creative tasks helped the children to describe their symptoms, generally using consistent language to do so, irrespective of age. Nineteen patient-reported outcome items were developed and subject to cognitive debriefing. Debriefing with both children and parents informed several small revisions and provided evidence that the majority of children found most patient-reported outcome items easy to understand, and that the items were mainly interpreted consistently and as intended. CONCLUSIONS: This in-depth qualitative study has supported identification of relevant symptom concepts and the development and refinement of patient-reported outcome items to assess those concepts. The findings support the content validity of the items and suggest that they can be used with confidence in children aged 9 years and older. For children aged 6-8 years, it is recommended the items are administered with initial adult supervision to explain the more difficult concepts or through parent/interviewer administration.

Capturing Gas Fluxes on Your Phone: An iOS- and Android-based Data-Logging Setup for EGM-4 Environmental Gas Monitoring Systems.

Mobile devices have become increasingly important for field monitoring to improve data capture efficiency, increase storage capacity, and replace heavy equipment. We introduce a quick and straightforward protocol to capture greenhouse gas (GHG) emission rates on mobile devices. We developed our setup on the widely used infrared gas analyzer (IRGA) EGM-4 by PP Systems. This IRGA has a limited internal storage capacity and requires an external device such as a laptop to conduct even modest field sampling. Furthermore, when raw data storage is required, carbon dioxide concentration resolution is reduced by the internal EGM-4 software settings, making the equipment less suitable for high-frequency measurements. Our protocol lets the user bring either an iOS or Android mobile device in to the field to connect to the EGM-4's data stream. For both platforms, a mobile console application was used to read, log, and share flux data. The raw data can be processed in either Python, R, or Matlab using the provided scripts that give the user flexibility to amend further postprocessing steps to obtain GHG fluxes. We demonstrate the flexible applicability of mobile devices for field recording and show that a cost-effective solution can enhance the operational life of superseded field equipment while also increasing the quality of the captured data.

Exploring the Impact of Infusion Frequency in Hemophilia A: Exit Interviews with Patients Participating in BAY 94-9027 Extension Studies (PROTECT VIII).

INTRODUCTION: Prophylactic treatment of severe hemophilia A is burdensome, requiring frequent intravenous injections. Extended half-life (EHL) factor VIII replacement therapies offer longer intervals between infusions while still meeting efficacy and safety outcomes; however, patient perspectives following long-term use of such products in the real-world remain unknown. OBJECTIVE: We aimed to explore the importance of infusion frequency and the potential benefits of reduced infusion frequency among patients receiving prophylactic treatment with an EHL product (BAY 94-9027). METHODS: Patients with severe hemophilia A participating in the PROTECT VIII extension study were invited to participate in a semi-structured, concept elicitation 'exit' interview to discuss their experiences. Participants were recruited from Israel, The Netherlands, and the US. Interview transcripts were translated into English and analyzed using thematic analysis methods. RESULTS: Sixteen participants (29-68 years of age) infusing with BAY 94-9027 once every 7 days, once every 5 days, or twice weekly were interviewed. Participants reported infusion frequency (alongside efficacy) as the most important treatment attribute influencing their satisfaction with therapy. Patient-reported benefits of reduced infusion frequency and longer duration of factor coverage included greater ability to participate in physical activities; better vein health; less time to schedule and administer factor VIII; reduced impact on work; and improved emotional well-being. CONCLUSIONS: This study provides rich insights into the experiences of patients with EHL products and the value of reduced infusion frequency. Such data could be of value to a range of stakeholders (e.g. regulators, payers) and facilitate patient-clinician discussions to promote tailored treatment decisions.