Point-of-care lung ultrasound in the assessment of suspected COVID-19: a retrospective service evaluation with a severity score.

INTRODUCTION: Point-of-care lung ultrasound (POCUS) has been advocated as a tool to assess the severity of COVID19 and thereby aid risk stratification. METHODS: We conducted a retrospective service evaluation between the 3rd March and the 5th May 2020 to describe and characterise the use of POCUS within an acute care pathway designed specifically for the assessment of suspected or confirmed COVID-19. A novel POCUS severity scale was formulated by assessing pleural and interstitial abnormalities within six anatomical zones (three for each lung). An aggregated score was calculated for each patient and evaluated as a marker of disease severity using standard metrics of discriminatory performance. RESULTS: POCUS was performed in the assessment of 100 patients presenting with suspected COVID-19. POCUS was consistent with COVID-19 infection in 92% (n = 92) of the patients assessed. Severity, as assessed by POCUS, showed good discriminatory performance to predict all-cause inpatient mortality, death or critical care admission, and escalated oxygen requirements (AUC .80, .80, 82). The risk of all-cause mortality in patients with scores in lowest quartile was 2.5% (95%CI 0.12- 12.95) compared with 42.9% (95CI 15.8 - 75.0%) in the highest quartile. POCUS assessed severity correlated with length of stay and duration of supplemental oxygen therapy. CONCLUSION: A simple aggregated score formed by the summating the degree of pleural and interstitial change within six anatomical lung zones showed good discriminatory performance in predicting a range of adverse outcomes in patients with suspected COVID-19.

OPTN/SRTR 2015 Annual Data Report: Lung.

In 2015, 2409 active candidates aged 12 years or older were added to the lung transplant waiting list; 2072 transplants were performed, the most of any year. The median waiting time for candidates listed in 2015 was 3.4 months; the shortest waiting time was for diagnosis group D. Despite the highest recorded transplant rate of 157 per 100 waitlist years, waitlist mortality continued a steady decade-long rise to a high of 16.5 deaths per 100 waitlist years. Measures of short- and long-term survival showed no trend toward improved overall survival in the past 5 years, except that 6-month death rates decreased from 9.4% in 2005 to 7.9% in 2014. At 5 years posttransplant, 55.5% of recipients remained alive. In 2015, 23 new child (ages 0-11 years) candidates were added to the list; 17 transplants were performed. Incidence of death was 6.1% at 6 months and 8.2% at 1 year for transplants in 2013-2014. Important policy changes will affect access to transplant. In February 2015, OPTN implemented a comprehensive revision of the lung allocation score to better reflect mortality risk. Broader geographic sharing of donor lungs for pediatric candidates and allowance for selected transplants across blood types for candidates aged younger than 2 years have been approved and are expected to improve pediatric access to transplant. The impact of these changes on lung transplant trends will be observed in the coming years.

OPTN/SRTR 2015 Annual Data Report: Heart.

The number of heart transplant candidates and transplants performed continued to rise each year. In 2015, 2819 heart transplants were performed. In addition, the number of new adult candidates on the waiting list increased 51% since 2004. The number of adult heart transplant survivors continued to increase, and in 2015, 29,172 recipients were living with heart transplants. Patient mortality following transplant has declined. The number of pediatric candidates and transplants performed also increased. New listings for pediatric heart transplants increased from 451 in 2004 to 644 in 2015. The number of pediatric heart transplants performed each year increased from 297 in 2004 to 460 in 2015. Among pediatric patients who underwent transplant in 2014, death occurred in 7.2% at 6 months and 9.6% at 1 year.

Gamification for health promotion: systematic review of behaviour change techniques in smartphone apps.

OBJECTIVE: Smartphone games that aim to alter health behaviours are common, but there is uncertainty about how to achieve this. We systematically reviewed health apps containing gaming elements analysing their embedded behaviour change techniques. METHODS: Two trained researchers independently coded apps for behaviour change techniques using a standard taxonomy. We explored associations with user ratings and price. DATA SOURCES: We screened the National Health Service (NHS) Health Apps Library and all top-rated medical, health and wellness and health and fitness apps (defined by Apple and Google Play stores based on revenue and downloads). We included free and paid English language apps using 'gamification' (rewards, prizes, avatars, badges, leaderboards, competitions, levelling-up or health-related challenges). We excluded apps targeting health professionals. RESULTS: 64 of 1680 (4%) health apps included gamification and met inclusion criteria; only 3 of these were in the NHS Library. Behaviour change categories used were: feedback and monitoring (n=60, 94% of apps), reward and threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%), social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and focus on past success (n=47, 73%). Median number of techniques per app was 14 (range: 5-22). Common combinations were: goal setting, self-monitoring, non-specific reward and non-specific incentive (n=35, 55%); goal setting, self-monitoring and focus on past success (n=33, 52%). There was no correlation between number of techniques and user ratings (p=0.07; rs=0.23) or price (p=0.45; rs=0.10). CONCLUSIONS: Few health apps currently employ gamification and there is a wide variation in the use of behaviour change techniques, which may limit potential to improve health outcomes. We found no correlation between user rating (a possible proxy for health benefits) and game content or price. Further research is required to evaluate effective behaviour change techniques and to assess clinical outcomes. TRIAL REGISTRATION NUMBER: CRD42015029841.

Brief Assessment of Parental Perception (BAPP): Development and validation of a new measure for assessing paediatric outcomes after bilateral cochlear implantation.

OBJECTIVE: In contrast to previous clinical practice, current guidelines recommend bilateral cochlear implantation in children, resulting in a cohort of children who initially received one implant, but have subsequently had a second, contralateral implant. This study aimed to explore satisfaction and quality of life in children implanted simultaneously or sequentially. DESIGN: A novel measure of satisfaction and quality of life following paediatric bilateral cochlear implantation (the Brief Assessment of Parental Perception; BAPP) was developed and preliminary validation undertaken as part of a large, national project of bilateral implantation. Children's parents completed the measure yearly for up to three years following implantation. STUDY SAMPLE: Children from 14 UK implant centres were recruited into the study; data were available for 410 children one year post-implantation. RESULTS: The BAPP was found to have good face and convergent validity, and internal consistency. Results indicated very high levels of satisfaction with the devices, and improvements in quality of life. However there was evidence that children implanted sequentially were less willing to wear their second implant in the first two years than those children receiving simultaneous implants. CONCLUSION: Simultaneous and sequential cochlear implants have a positive impact on the quality of life of deaf children.

The OPTN Deceased Donor Potential Study: Implications for Policy and Practice.

The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.

OPTN/SRTR 2013 Annual Data Report: lung.

Lungs are allocated to adult and adolescent transplant candidates (aged ⩾ 12 years) on the basis of age, geography, blood type compatibility, and the lung allocation score (LAS), which reflects risk of waitlist mortality and probability of posttransplant survival. In 2013, the most adult candidates, 2394, of any year were added to the list. Overall median waiting time for candidates listed in 2013 was 4.0 months. The preferred procedure remained bilateral lung transplant, representing approximately 70% of lung transplants in 2013. Measures of short-term and longterm survival have plateaued since the implementation of the LAS in 2005. The number of new child candidates (aged 0-11 years) added to the lung transplant waiting list increased to 39 in 2013. A total of 28 lung transplants were performed in child recipients, 3 for ages younger than 1 year, 9 for ages 1 to 5 years, and 16 for ages 6 to 11 years. The diagnosis of pulmonary hypertension was associated with higher survival rates than cystic fibrosis or other diagnosis (pulmonary fibrosis, bronchiolitis obliterans, bronchopulmonary dysplasia). For child candidates, infection was the leading cause of death in year 1 posttransplant and graft failure in years 2 to 5.

OPTN/SRTR 2013 Annual Data Report: heart.

The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 34.2% from 2003 to 2013. The heart transplant rate among active adult candidates peaked at 149.0 per 100 waitlist years in 2007 and has been declining since then; in 2013, the rate was 87.4 heart transplants per 100 active waitlist years. Increased waiting times do not appear to be correlated with an overall increase in waitlist mortality. Since 2008, the proportion of patients on life support before transplant increased from 53.4% to 65.8% in 2013. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately 500 pediatric candidates are added to the waiting list each year; the number of pediatric transplants performed each year increased from 293 in 2003 to 411 in 2013. Patient survival among pediatric recipients continues to improve; 5-year patient survival for transplants performed from 2001 through 2008 was 70% to 80%. Medicare paid for some or all of the care for 42.2% of all heart transplant recipients in 2012.

The future direction of the adult heart allocation system in the United States.

Ensuring equitable and fair organ allocation is a central charge of the United Network for Organ Sharing (UNOS) as the Organ Procurement and Transplantation Network (OPTN) through its contract with the Department of Health and Human Services (DHHS). The OPTN/UNOS Board initiated a reassessment of the current allocation system. This paper describes the efforts of the OPTN/UNOS Heart Subcommittee, acting on behalf of the OPTN/UNOS Thoracic Organ Transplantation Committee, to modify the current allocation system. The Subcommittee assessed the limitations of the current three-tiered system, outcomes of patients with status exceptions, emerging ventricular assist device (VAD) population, options for improved geographic sharing and status of potentially disenfranchised groups. They analyzed waiting list and posttransplant mortality rates of a contemporary cohort of patient groups at risk, in collaboration with the Scientific Registry of Transplant Recipients to develop a proposed multi-tiered allocation scheme. This proposal provides a framework for simulation modeling to project whether candidates would have better waitlist survival in the revised allocation system, and whether posttransplant survival would remain stable. The tiers are subject to change, based on further analysis by the Heart Subcommittee and will lead to the development of a more effective and equitable heart allocation system.

Report from a forum on US heart allocation policy.

Since the latest revision in US heart allocation policy (2006), the landscape and volume of transplant waitlists have changed considerably. Advances in mechanical circulatory support (MCS) prolong survival, but Status 1A mortality remains high. Several patient subgroups may be disadvantaged by current listing criteria and geographical disparity remains in waitlist time. This forum on US heart allocation policy was organized to discuss these issues and highlight concepts for consideration in the policy development process. A 25-question survey on heart allocation policy was conducted. Among attendees/respondents were 84 participants with clinical/published experience in heart transplant representing 51 US transplant centers, and OPTN/UNOS and SRTR representatives. The survey results and forum discussions demonstrated very strong interest in change to a further-tiered system, accounting for disadvantaged subgroups and lowering use of exceptions. However, a heart allocation score is not yet viable due to the long-term viability of variables (used in the score) in an ever-developing field. There is strong interest in more refined prioritization of patients with MCS complications, highly sensitized patients and those with severe arrhythmias or restrictive physiology. There is also strong interest in distribution by geographic boundaries modified according to population. Differences of opinion exist between small and large centers.

OPTN/SRTR 2012 Annual Data Report: heart.

The number of heart transplants performed annually continues to increase gradually, and the number of adult candidates on the waiting list increased by 25% from 2004 to 2012. The heart transplant rate among active adult candidates peaked at 149 per 100 wait-list years in 2007 and has been declining since; in 2012, the rate was 93 heart transplants per 100 active wait-list years. Increased waiting times do not appear to be correlated with an overall increase in wait-list mortality. Since 2007, the proportion of patients on life support before transplant increased from 48.6% to 62.7% in 2012. Medical urgency categories have become less distinct, with most patients listed in higher urgency categories. Approximately 500 pediatric candidates are added to the waiting list each year; the number of transplants performed each year increased from 274 in 1998 to 372 in 2012. Graft survival in pediatric recipients continues to improve; 5-year graft survival for transplants performed in 2007 was 78.5%. Medicare paid for some or all of the care for nearly 40% of heart transplant recipients in 2010. Heart transplant appears to be more expensive than ventricular assist devices for managing end-stage heart failure, but is more effective and likely more cost-effective.

OPTN/SRTR 2012 Annual Data Report: lung.

Lung transplants are increasingly used as treatment for end-stage lung diseases not amenable to other medical and surgical therapies. Lungs are allocated to adult and adolescent transplant candidates on the basis of age, geography, blood type compatibility, and the Lung Allocation Score, which reflects risk of wait-list mortality and probability of posttransplant survival. The overall median waiting time in 2012 was 4 months, and 65.3% of candidates underwent transplant within 1 year of listing; however, this proportion varied greatly by donation service area. Unadjusted median survival of lung transplant recipients was 5.3 years in 2012, and median survival conditional on living for 1 year posttransplant was 6.7 years. Among pediatric lung candidates in 2012, 32.1% were wait-listed for less than 1 year, 17.9% for 1 to less than 2 years, 16.7% for 2 to less than 4 years, and 33.3% for 4 or more years. Both graft and patient survival have continued to improve; survival rates for recipients aged 6-11 years are better than for younger recipients. Compared with recipients of other solid organ transplants, lung transplant recipients experienced the highest rates of rehospitalization for transplant complications: 43.7 per 100 patients in year 1 and 36.0 in year 2.

Lung transplantation in the United States, 1998-2007.

This article highlights trends and changes in lung and heart-lung transplantation in the United States from 1998 to 2007. The most significant change over the last decade was implementation of the Lung Allocation Score (LAS) allocation system in May 2005. Subsequently, the number of active wait-listed lung candidates declined 54% from pre-LAS (2004) levels to the end of 2007; there was also a reduction in median waiting time, from 792 days in 2004 to 141 days in 2007. The number of lung transplants performed yearly increased through the decade to a peak of 1 465 in 2007; the greatest single year increase occurred in 2005. Despite candidates with increasingly higher LAS scores being transplanted in the LAS era, recipient death rates have remained relatively stable since 2003 and better than in previous years. Idiopathic pulmonary fibrosis became the most common diagnosis group to receive a lung transplant in 2007 while emphysema was the most common diagnosis in previous years. The number of retransplants and transplants in those aged > or =65 performed yearly have increased significantly since 1998, up 295% and 643%, respectively. A decreasing percentage of lung transplant recipients are children (3.5% in 2007, n = 51). With LAS refinement ongoing, monitoring of future impact is warranted.

Adolescent's stress responses and psychological functioning when a parent has early breast cancer.

OBJECTIVE: To identify factors associated with psychological functioning in adolescent children of early-stage breast cancer patients. METHOD: Adolescents' self-reported psychological functioning using the Child Behaviour Checklist (YSR), Mental Health subscale of the Child Health Questionnaire (CHQ-MH) and Child Impact of Events (C-IES) scale. The Family Assessment Device (FAD) and the Family Environment Scale (FES cohesion subscale) assessed family functioning. Maternal depression was assessed on the Beck Depression Inventory (BDI) and quality of life using the SF8. Using a cross-sectional within-groups design, assessments were obtained for 56 adolescents of 11-17 years . RESULTS: High rates of stress were found (C-IES) in 33% males and 45% females. Thirty percent of adolescents reported psychological problems (YSR) (28% males and 32% females) when compared with published norms. Poor family functioning was linked with YSR internalising and externalising problems; poor family cohesion with higher externalising and total YSR psychological problems. Maternal depression was linked with adolescent-reported internalising problems. CONCLUSIONS: When mothers have breast cancer, a substantial minority of their adolescent children have psychological and stress response-related problems linked with poor family functioning. These results argue in favour of a family-oriented approach to psychological support of breast cancer patients.

Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers.

Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.

Development of the new lung allocation system in the United States.

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.

Cost effectiveness analysis of neonatal extracorporeal membrane oxygenation based on four year results from the UK Collaborative ECMO Trial.

OBJECTIVE: To assess the cost effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure over a four year time span. DESIGN: Cost effectiveness analysis based on a randomised controlled trial in which infants were individually allocated to ECMO (intervention) or conventional management (control) and then followed up to 4 years of age. SETTING: Infants were recruited from 55 approved recruiting hospitals throughout the United Kingdom. Infants allocated to ECMO were transferred to one of five specialist regional centres. Follow up of surviving infants was performed in the community. SUBJECTS: A total of 185 mature (gestational age at birth >or= 35 weeks, birth weight >or= 2000 g) newborn infants with severe respiratory failure (oxygenation index >or= 40). MAIN OUTCOME MEASURES: Incremental cost per additional life year gained; incremental cost per additional disability-free life year gained. RESULTS: Over four years, the policy of neonatal ECMO was effective at reducing known death or severe disability (relative risk = 0.64; 95% confidence interval 0.47 to 0.86; p = 0.004). After adjustment for censoring and discounting at 6%, the mean additional health service cost of neonatal ECMO was pound 17367 (95% confidence interval pound 12072 to pound 22224) per infant ( pound UK, 2001 prices). Over four years, the incremental cost of neonatal ECMO was pound 16707 ( pound 9828 to pound 37924) per life year gained and pound 24775 ( pound 13106 to pound 69690) per disability-free life year gained. These results remained robust after variations in the values of key variables performed as part of a sensitivity analysis. CONCLUSIONS: The study provides rigorous evidence of the cost effectiveness of ECMO at four years for mature infants with severe respiratory failure.

Importance of access to research information among individuals with spinal cord injury: results of an evidenced-based questionnaire.

OBJECTIVE: To assess the interests and accessibility of patients with a spinal cord injury (SCI) to information in different areas of SCI. SETTING: Spinal Program, Toronto Western Hospital, University Health Network. METHODS: An interest assessment survey and the SF-36 (short form-36) questionnaire were mailed to SCI patients living in the community. The interest assessment examined patients' interest in information in many areas related to SCI, their current knowledge in these areas and the accessibility of different information formats. RESULTS: Fourteen patients (45%) completed the questionnaires. Regardless of physical or mental health status, all patients expressed a high level of interest in SCI research and clinical trials. An Internet website proved to be the most preferred, accessible and comfortable information format for these patients. Patients expressed a lower interest in support groups and organizations. Results from the SF-36 showed poor social functioning was related to interest in support groups, and poor general health perception was related to interest in occupational and physical therapy. CONCLUSION: The majority of SCI patients have a high interest in accessing SCI research information. The Internet is a favorable, comfortable and accessible tool for providing this information and will benefit all SCI patients. These results suggest that a significant number of patients with SCI would benefit from an accessible Internet-based information database that is relevant to the SCI patients population.

Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma.

OBJECTIVE: To compare the relative value of an inhaled corticosteroid, fluticasone propionate 88 microg twice daily, versus an oral leukotriene receptor antagonist, zafirlukast 20 mg twice daily, in patients with persistent asthma currently receiving short acting beta2-agonists alone. STUDY DESIGN: A cost-efficacy analysis using resource utilisation and clinical data obtained prospectively from a multicentre, randomised, double-blind, double-dummy, placebo-controlled 12-week clinical trial conducted in the US. PERSPECTIVE: Third-party payor. PATIENTS AND METHODS: A total of 451 corticosteroid-naive patients with persistent asthma were treated with either fluticasone propionate 88 microg twice daily or zafirlukast 20 mg twice daily. All patients were given salbutamol (albuterol) to be used as rescue medication. Data were examined using intent-to-treat analysis. RESULTS: Mean daily per person cost-efficacy ratios using improvement in forced expiratory volume in 1 second (FEV1) [> or = 12% increase from baseline] were $US 3.47 for fluticasone propionate compared with $US 7.81 for zafirlukast (1999 values). The mean daily per person cost-efficacy ratios for symptom-free days obtained were $US 5.51 for fluticasone propionate compared with $US 14.98 for zafirlukast. These cost-efficacy ratios remained in favour of fluticasone propionate after a robust sensitivity analysis. CONCLUSIONS: Treatment with fluticasone propionate 88 kg twice daily was the most cost effective treatment compared with zafirlukast 20 mg twice daily in this 12-week clinical trial. This analysis supports the use of fluticasone propionate 88 microg twice daily as first-line treatment in patients with persistent asthma previously treated with short-acting beta2-agonist alone.

Improvement in health care utilization and pulmonary function with fluticasone propionate in patients with steroid-dependent asthma at a National Asthma Referral Center.

The impact of switching from other inhaled corticosteroids to fluticasone propionate was studied in patients with severe oral-steroid-dependent asthma over a 1-year period. In this open-label prospective study, patients on maintenance doses of oral and inhaled steroids were referred to a national asthma treatment center and were switchedfrom their previous inhaled corticosteroid to fluticasone propionate 880 microg BID. Compared with data collected from the year prior to enrollment, treatment with fluticasone propionate resulted in significant improvements in pulmonary function, oral steroid requirements, and health resource utilization. In addition, five patients were completely weaned off oral steroids.