Exploring patient reported quality of life in lung cancer patients: A qualitative study of patient-reported outcome measures.

OBJECTIVE: Lung cancer is the leading cause of cancer-related death globally and provides a major disease burden likely to substantially impact quality of life (QoL). Patient-reported outcome measures (PROMs) have been identified as effective methods of evaluating patient QoL. Existing lung cancer-specific PROMs however have uncertain utility and minimal patient involvement in their design and development. This qualitative study aimed to evaluate the patient perspective of existing PROMs and to explore their appropriateness for population-based descriptions of lung cancer-related QoL. METHODS: A descriptive qualitative study was conducted consisting of semi-structured interviews with 14 patients recruited from the Victorian Lung Cancer Registry and Alfred Hospital using purposive sampling. Interviews first explored the factors most important to lung cancer patients QoL, and second, patient's perspectives on the appropriateness of existing PROMs. Thematic analysis was used to develop themes, and content analysis was conducted to determine PROM acceptability. RESULTS: Five novel themes were identified by patients as being important impacts on QoL: Personal attitude toward the disease is important for coping; independence is valued; relationships with family and friends are important; relationships with treating team are meaningful; personal and public awareness of lung cancer is limited. These patient-identified impacts are poorly covered in existing lung cancer-specific PROMs. Patients welcomed and appreciated the opportunity to complete PROMs; however, they identified problems with existing PROMs relevance, tone, and formatting. CONCLUSION: Existing lung cancer PROMs poorly reflect the five themes identified in this study as most important to lung cancer patients QoL. This study reaffirms the need to review existing PROMs to ensure utility and construct validity. Future PROM development must engage key patient-generated themes and evolve to reflect the changing management and therapeutic landscape.

Understanding the research capacity of alcohol and other drugs services in New South Wales, Australia.

INTRODUCTION: Enhancing health system research capacity can support improved quality care. This study assessed the research capacity of public local health district (LHD) and non-government organisation (NGO) alcohol and other drug (AOD) services, at the organisational, team and individual level. Research barriers and motivators were also examined. METHODS: Staff from LHD and NGO AOD treatment services in New South Wales completed an online survey using the Research Capacity and Culture (RCC) tool. Overall median research capacity scores are presented for the RCC subscales (organisational, team and individual). Comparisons were conducted by service type (LHD/NGO), geographical location (metropolitan/rural) and affiliation with a research network (yes/no). Qualitative questions explored barriers and motivators to research at individual and team levels. RESULTS: Of 242 participants, 55% were LHD-based and 45% NGO-based. Overall RCC scores indicated moderate research capacity at all levels. Organisational capacity (Med = 6.50, interquartile range [IQR] = 3.50) scored significantly higher than the team (Med = 5.00, IQR = 6.00) and individual level (Med = 5.00, IQR = 4.25). No differences in RCC scores existed between NGOs and LHDs. Metropolitan AOD services scored higher research capacity at the organisational level (Med = 7.00, IQR = 3.00) than rural services (Med = 5.00, IQR = 5.00). LHDs affiliated with a research network scored significantly higher at the organisational, team and individual level than non-affiliated LHD services. Key research barriers were inadequate time and funding. Motivators included skill development and problem-identification requiring change. DISCUSSIONS AND CONCLUSIONS: AOD services in New South Wales have moderate research capacity. Identified barriers and motivators can be used to target responses that enhance capacity and improve treatment outcomes.

Approaching easy water disinfection for all: Can in situ electrochlorination outperform conventional chlorination under realistic conditions?

Electrochlorination has gained research interest for its potential application as decentralized water treatment. A number of studies have displayed promising efficiency for water disinfection. However, a comprehensive comparison of in situ electrodisinfection to existing disinfection techniques, particularly under realistic water composition and flow rates, still needs additional research efforts. The aim of this study is to evaluate in situ electrochlorination while comparing the treatment with conventional chemical chlorination for point-of-entry decentralized disinfection at the household level. An electrochemical flow cell reactor was operated in a single pass mode considering water flow and water consumption for a household of four family members. Disinfection efficiency assessment of both electrochemical and chemical chlorination was conducted using bacterial and viral surrogates, E. coli and MS2 bacteriophage. Furthermore, a techno-economic analysis was conducted, using the levelized cost of water, to compare two electrochemical chlorination scenarios (i.e., electrical grid energy use, and solar panel powered system) and benchmarked against the baseline treatment of chemical chlorination. The findings revealed increased inactivation efficiency of in situ electrochlorination over conventional chlorination (p-value < 0.05). The synergetic impact of radicals and chlorine, and/or contribution of high chlorine concentration at acidic pH near anode surface were identified as key factors that could enhance disinfection performance of in situ electrochlorination. The techno-economic analysis demonstrated that electrochemical treatment, when operated using renewable energy sources, is not only a more environmentally sustainable approach, but also emerges as a more economically feasible solution for decentralized water treatment application. The results highlight that in situ electrochlorination is a more advanced alternative to decentralized water chlorination. However, further fundamental research on products and by-products formation under various water matrices is required.

Machine Learning Techniques to Predict Timeliness of Care among Lung Cancer Patients.

Delays in the assessment, management, and treatment of lung cancer patients may adversely impact prognosis and survival. This study is the first to use machine learning techniques to predict the quality and timeliness of care among lung cancer patients, utilising data from the Victorian Lung Cancer Registry (VLCR) between 2011 and 2022, in Victoria, Australia. Predictor variables included demographic, clinical, hospital, and geographical socio-economic indices. Machine learning methods such as random forests, k-nearest neighbour, neural networks, and support vector machines were implemented and evaluated using 20% out-of-sample cross validations via the area under the curve (AUC). Optimal model parameters were selected based on 10-fold cross validation. There were 11,602 patients included in the analysis. Evaluated quality indicators included, primarily, overall proportion achieving "time from referral date to diagnosis date ≤ 28 days" and proportion achieving "time from diagnosis date to first treatment date (any intent) ≤ 14 days". Results showed that the support vector machine learning methods performed well, followed by nearest neighbour, based on out-of-sample AUCs of 0.89 (in-sample = 0.99) and 0.85 (in-sample = 0.99) for the first indicator, respectively. These models can be implemented in the registry databases to help healthcare workers identify patients who may not meet these indicators prospectively and enable timely interventions.

Mapping the clinical care pathways for advanced stage non-small cell lung cancer patients in Victoria: A retrospective cohort study of supportive and palliative care.

The lung cancer Optimal Care Pathway recommends supportive care and palliative care integration throughout its various steps, with early referral to appropriate services improving the quality of life in advanced stage non-small cell lung cancer patients. Using Victorian Lung Cancer Registry data and linked administrative datasets, this retrospective cohort study mapped clinical care pathways of 525 Stage III-IV non-small cell lung cancer patients in Victoria to 11 recommendations in the Optimal Care Pathway, identifying unwarranted variations in clinical care. Supportive care and palliative care delivery were further examined to understand the involvement and timing of specialist care teams. Our findings showed that palliative care utilization is highest at the time of treatment, despite recommendations that it should be provided early after diagnosis to improve patient outcomes and satisfaction. Early supportive care screening was observed in half the cohort and almost three-quarters of the patients had been presented at a multidisciplinary meeting. Multidisciplinary meeting presentations and supportive care provide an opportunity to improve communication about palliative care needs and integration into routine clinical practice, such as at the time of treatment planning.

Persisting Gaps in Optimal Care of Stage III Non-small Cell Lung Cancer: An Australian Patterns of Care Analysis.

BACKGROUND: Wide variation exists globally in the treatment and outcomes of stage III patients with non-small cell lung cancer (NSCLC). We conducted an up-to-date patterns of care analysis in the state of Victoria, Australia, with a particular focus on the proportion of patients receiving treatment with radical intent, treatment trends over time, and survival. MATERIALS AND METHODS: Stage III patients with NSCLC were identified in the Victorian Lung Cancer Registry and categorized by treatment received and treatment intent. Logistic regression was used to explore factors predictive of receipt of radical treatment and the treatment trends over time. Cox regression was used to explore variables associated with overall survival (OS). Covariates evaluated included age, sex, ECOG performance status, smoking status, year of diagnosis, Australian born, Aboriginal or Torres Strait Islander status, socioeconomic status, rurality, public/private status of notifying institution, and multidisciplinary meeting discussion. RESULTS: A total of 1396 patients were diagnosed between 2012 and 2019 and received treatment with radical intent 67%, palliative intent 23%, unknown intent 5% and no treatment 5%. Radical intent treatment was less likely if patients were >75 years, ECOG ≥1, had T3-4 or N3 disease or resided rurally. Surgery use decreased over time, while concurrent chemoradiotherapy and immunotherapy use increased. Median OS was 38.0, 11.1, and 4.4 months following radical treatment, palliative treatment or no treatment, respectively. CONCLUSION: Almost a third of stage III patients with NSCLC still do not receive radical treatment. Strategies to facilitate radical treatment and better support decision making between increasing multimodality options are required.

Prioritizing measures to assess performance of drug treatment services: a Delphi process with funders, treatment providers and service-users.

BACKGROUND AND AIM: While many studies have examined outcome measurement as part of clinical trials and routine outcome collection at the person-level in alcohol and other drug (AOD) treatment services, there has been limited attention to measures required to assess performance at the service-level. In Australia, non-government services are primarily funded by government using public funds; however, there is no standardized approach to performance measurement. This study sought to establish a finite list of performance measures that represented consensus between funders, treatment providers and service-users. METHOD: A three-round Delphi process was undertaken with (i) funders of treatment (n = 10), (ii) treatment providers (n = 10) and (iii) treatment service-users (n = 10). Participants were asked to rate a range of measures on a 10-point Likert scale on how important they were to be included in contracts with funders. Measures with a median score > 7 and agreement among participants above 70% were the criteria for inclusion in the final set of measures. Qualitative data in the form of text responses provided by participants for their ratings in rounds 1 and 2 were also analysed. RESULTS: Participants rated 93 measures in round 1, which reduced to 78 measures in round 2 and 32 measures in round 3. Fifteen service-level measures and two system-level measures met criteria for inclusion in the final set of performance measures. The final set of measures cover a range of measurement types: outcomes (n = 5), access (n = 3), structural (n = 3), experience (n = 2), input (n = 2), process (n = 1) and output (n = 1). CONCLUSION: In Australia, performance measures for alcohol and other drug treatment services that represent a consensus among service-users, providers and funders focus upon demonstrating accountability for public funds, improving services and communicating key measures of success to future service-users and the broader community.

GM-CSF antibodies in artificial stone associated silicoproteinosis: A case report and literature review.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease where there is accumulation of surfactant in the alveoli. It can be classified based on the underlying aetiology into three categories: primary, secondary and congenital. Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF-Ab) are a key diagnostic feature of autoimmune PAP. High intensity occupational exposure and inhalation of toxic particles such as silica can cause a form of secondary PAP called acute silicoproteinosis. We describe a 26-year-old stone benchtop fabricator with silicoproteinosis following daily exposure to high levels of silica who had elevated serum GM-CSF-Ab. We discuss the role of GM-CSF-Ab in cases of PAP with occupational inhalational exposure and the challenges in its interpretation.

Nebulised sargramostim in pulmonary alveolar proteinosis.

Five patients, comprising nine treatment courses of sargramostim use in pulmonary alveolar proteinosis, are described. The prevailing standard of treatment, whole lung lavage (WLL), is highly invasive, resource intensive and carries some procedural risk. Nebulised recombinant human GM-CSF (sargramostim) offers a pharmacological treatment option, allowing patients to be treated at home, possessing potential advantages in patient experience and wider health resourcing. The majority of reported patients described subjective improvement in symptoms along with radiographical improvement, although this did not translate into significant improvement in pulmonary function testing. Drug scarcity and high drug cost remain potential barriers to accessing this treatment, and so careful patient selection and treatment outcome assessment remain as challenging needs. Incorporating the routine assessment of validated patient symptom scores with objective physiological measures will allow prediction of response to treatment and help guide management. This report describes the largest published experience of sargramostim use in Australia.

A comparison of outcomes and survival between Victoria and Denmark in lung cancer surgery: opportunities for international benchmarking.

BACKGROUNDS: Victoria (Australia) and Denmark have comparable population sizes and high-quality healthcare systems. Lung cancer surgery, however, is performed in more than 20 Victorian hospitals compared to four in Denmark. Such differences in centralization may influence outcomes. We engaged clinical quality registries to enable international benchmarking by exploring patterns of lung cancer surgery including mortality and survival. METHODS: All patients undergoing lung cancer surgery between 2015 and 2018 registered in the Victorian Lung Cancer Registry and the Danish Lung Cancer Registry were included. Analyses on stage concordance, 30 and 90-day mortality, and overall survival were restricted to a selected subgroup with NSCLC and no neo-adjuvant therapy or metastatic disease and only one operation. RESULTS: We included 1554 Victorian and 4319 Danish patients. The resection rate was 26.3% in Victoria and 28% in Denmark, but a higher proportion of Victorian patients underwent wedge resection (19.1% versus 8.8%). Stage concordance was 59.6% and 54.9% in Victoria and Denmark, respectively. The 30- and 90-day mortality was 1.3% and 2.6% in Victoria, compared to 1.4% and 2.8% in Denmark with no difference in overall survival (p = 0.28) or risk-adjusted survival (HR: 1.10 (95% CI: 0.89-1.37); p = 0.38). CONCLUSION: High-quality surgical lung cancer care was confirmed by similar high resection and low mortality rates including no overall survival difference. The drivers and consequences of stage discordance and differences in patterns of resection deserve further exploration. This study provides a model for international benchmarking using clinical quality registries, although caution remains in the interpretation given disparities in data completeness.

The clinical impact of self-reported symptoms of chronic rhinosinusitis in people with bronchiectasis.

BACKGROUND: Chronic rhinosinusitis affects 62% of adults with bronchiectasis and is linked to greater bronchiectasis severity. However, the impact of symptoms of chronic rhinosinusitis on disease-specific and cough-related quality of life is unknown. METHODS: In this cross-sectional study, adults with stable bronchiectasis and chronic rhinosinusitis symptoms completed the sinonasal outcome test-22 (SNOT-22), quality of life-bronchiectasis questionnaire, and Leicester cough questionnaire. Bronchiectasis severity was assessed using the bronchiectasis severity index (BSI) and chest high-resolution computed tomography (HRCT). RESULTS: Sixty participants with bronchiectasis (mean [SD] forced expiratory volume in 1 s of 73.2 [25.5] %predicted) were included. Greater severity of chronic rhinosinusitis symptoms (based on SNOT-22) was moderately associated with impaired cough-related quality of life (according to the Leicester cough questionnaire; all r > -.60) and impaired bronchiectasis-specific quality of life (based on the quality of life-bronchiectasis questionnaire), with impaired physical function (r = -.518), less vitality (r = -.631), reduced social function (r = -.546), greater treatment burden (r = -.411), and increased severity of respiratory symptoms (r = -.534). Chronic rhinosinusitis symptoms were unrelated to disease severity according to the BSI (r = .135) and HRCT scoring (all r < .200). The severity of chronic rhinosinusitis symptoms was not affected by sputum color (p = .417) or the presence of Pseudomonas aeruginosa colonization (p = .73). CONCLUSIONS: In adults with bronchiectasis, chronic rhinosinusitis has a consistent and negative impact on both cough-related and bronchiectasis-specific quality of life.

Impacts of lung cancer multidisciplinary meeting presentation: Drivers and outcomes from a population registry retrospective cohort study.

INTRODUCTION: Multidisciplinary Meetings (MDM) are recommended in routine lung cancer care, however its broader impacts demand further evaluation. We assessed the drivers and impacts of MDM presentation in the Victorian Lung Cancer Registry (VLCR). METHODS: We examined the effect of MDM presentation on receipt of treatment and survival in VLCR patients diagnosed between 2011 and 2020. We compared patient characteristics, drivers of MDM discussion and survival between the two groups. RESULTS: Of 9,628 patients, 5,900 (61.3%) were discussed at MDM, 3,728 (38.7%) were not. In the non-MDM group, a lower proportion received surgery (22.1% vs. 31.2%), radiotherapy (34.2% vs. 44.4%) and chemotherapy (44.7% vs. 49.0%). Patients were less likely to be discussed if ≥80 years (OR 0.73, p < 0.001), of ECOG performance status (PS) 4 (OR 0.23, p < 0.001), clinical stage IV (OR 0.34, p < 0.001) or referred from regional (OR 0.52, p < 0.001) or private hospital (OR 0.18, p < 0.001). MDM-presented patients had better median survival (1.70 vs 0.75 years, p < 0.001) and lower adjusted mortality risk (HR 0.75; 0.71-0.80, p < 0.001), a protective effect consistent across all hospital types. Undocumented PS, histopathology and clinical stage were associated with lower likelihood of MDM discussion and worse mortality. CONCLUSIONS: In the VLCR, being male, ≥80 years, of poorer PS, advanced clinical stage and poor clinical characterisation significantly disadvantaged patients in relation to MDM discussion. MDM-discussed patients were more likely to undergo treatment and had a 25% lower risk of mortality. This study supports the use of MDMs in lung cancer and identifies areas of inequity to be addressed.

Measurement properties of the 12-item Short Form Health Survey version 2 in Australians with lung cancer: a Rasch analysis.

BACKGROUND: The 12-item Short-Form Health Survey version 2 (SF-12v2), a widely used, generic patient-reported measure of health status that provides summary scores of physical and mental health. No study to date has examined the measurement properties of the SF-12v2 in patients with lung cancer using Rasch analysis. The aim of this study was to extend the psychometric evaluations of the SF-12 within the lung cancer population to ensure its validity and reliability to assess the health status in this population. METHODS: Participants in the Victorian Lung Cancer Registry (VLCR) who completed the SF-12v2 between 2012 and 2016 were included in this study. The structural validity of the SF-12v2 was assessed using Rasch analysis. Overall fit to the Rasch measurement model was examined as well as five key measurement properties: uni-dimensionality, response thresholds, internal consistency, measurement invariance and targeting. RESULTS: A total of 342 participants completed the SF-12v2 three months following their lung cancer diagnosis. The SF-12 Physical Component Score (PCS-12) did not fit the overall Rasch measurement model (χ2 107.0; p < 0.001). Three items deviated significantly from the Rasch model (item fit residual beyond ± 2.5) with signs of dependency between item responses and disordered thresholds. Nevertheless, the PCS-12 was uni-dimensional with good internal consistency (person separation index [PSI] 0.83) and reasonable targeting. In contrast, the SF-12 Mental Component Score (MCS-12) had good overall model fit (χ2 35.1; p = 0.07), reasonable targeting and good internal consistency (PSI 0.81). CONCLUSIONS: Rasch analysis suggests that there is general support for the reliability of the SF-12v2 as a measure of physical and mental health in people with lung cancer. However, the appropriateness of some items (e.g. pain) in the PCS-12 is questionable and further refinement of the scale including changing the response options may be required to improve the ability of the SF-12v2 to more appropriately assess the health status of this population.

Impacts of multidisciplinary meeting case discussion on palliative care referral and end-of-life care in lung cancer: a retrospective observational study.

BACKGROUND: Multidisciplinary meeting (MDM) discussion and early palliative care are recommended in lung cancer management. The literature is unclear whether MDM discussion leads to early palliative care and improved end-of-life care. AIMS: To evaluate impacts of discussion at an Australian lung MDM on palliative care referral, and MDM and early palliative care on aggressive end-of-life care. METHODS: A retrospective, cross-sectional study was conducted of 352 patients diagnosed with primary lung cancer from 2017 to 2019 at the Alfred Hospital, Melbourne. The primary question was whether MDM discussion influenced palliative care referrals. Secondary questions were whether MDM discussion and early palliative care reduced aggressive treatment (chemotherapy, hospitalisation, emergency department visits, intensive care admission and in-hospital death) during the last 30 days of life. Multivariable logistic regression was used to determine independent association between MDM discussion and palliative care referral. RESULTS: MDM discussion did not independently impact palliative care referral. There was reduced likelihood of MDM presentation in patients with metastatic disease (P < 0.0001) and poorer performance status (P = 0.025), and higher likelihood of palliative care referral in these patients (both P < 0.001). MDM discussion reduced end-of-life intensive care unit (ICU) admission in patients with metastatic disease (P = 0.04). A palliative care referral-to-death interval of ≥30 days was associated with reduced hospitalisation at the end of life (P < 0.0001) and hospital deaths (P = 0.001). CONCLUSION: Discussion at lung MDM did not increase palliative care referral, but did reduce ICU admission among metastatic patients at the end of life. Longer palliative care referral-to-death interval was associated with reduced aggressive end-of-life care. Further research is needed in these areas.

Influenza-specific IgG1+ memory B-cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency.

BACKGROUND: Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen-specific response. OBJECTIVE: To quantify and characterise the antigen-specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination. METHODS: Recombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells. RESULTS: Recombinant HA tetramers were specifically recognised by 0.5-1% of B cells in previously vaccinated healthy adults. HA-specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HA-specific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination. CONCLUSION: We have successfully identified AM15-specific Bmem cells in healthy controls and PAD patients. The presence of antigen-specific Bmem cells could offer an additional diagnostic tool to aid in the clinical diagnosis of PAD. Furthermore, alterations in the number or immunophenotype of HA-specific Bmem cells post-booster vaccination could assist in the evaluation of immune responses in individuals receiving IgRT.

Contracting treatment services in Australia: Do measures adhere to best practice?

BACKGROUND: Contracting non-government services to provide alcohol and other drug (AOD) treatment requires the specification of performance measures to ensure accountability for public funds. There is currently no standardised approach by funders to the measurement of performance of AOD treatment in Australia. Funding to non-government organisations (NGOs) is complex, with NGOs managing funding agreements from a range of sources that contain a large number of differing performance measures. This study aimed to assess performance measures used in contracts for NGO AOD treatment providers and how they align with best practice. METHODS: Performance measures contained in funding agreements for treatment providers were collected from a diverse sample of both funders (n=8) and treatment providers (n=20) resulting in more than 1,100 measures. The list of measures was synthesized to a finite, non-duplicative list (n=537). Measures were assessed by three raters against 11 criteria (for example, measurable and timely) documented as best practice elements of performance measures (Council of Australian Governments, 2011a). Measures were also coded into different measurement types (such as outcome and process). RESULTS: None of the 537 unique performance measures used in funding agreements for treatment providers fully met the criteria for best practice in performance measurement. Whilst the literature and government policy is being directed towards outcomes-based funding and reporting, only 7.6% of measures were classified as outcome measures. The majority of measures were classified at output (41.3%) and process (23.6%) measures. CONCLUSION: Current measures in contracts applied by funders to treatment services do not adhere to best practice. The development and implementation of new performance measures is required to inform AOD policy and accountability of public funds. Further, identifying more robust performance measures has the potential to lead to reduced reporting burden on service providers and better monitoring of service quality and outcomes.

Summary of the NACI Statement on the Use of Bivalent Factor H Binding Protein Meningococcal Serogroup B (MenB-fHBP) Vaccine for the Prevention of Meningococcal B Disease.

BACKGROUND: TrumenbaTM, a bivalent, factor-H binding protein meningococcal serogroup B (MenB-fHBP) vaccine was authorized for use in Canada in October 2017 for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B in individuals 10-25 years of age. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of meningococcal vaccines to the Public Health Agency of Canada. OBJECTIVE: To summarize NACI recommendations regarding the use of MenB-fHBP vaccine in Canada. METHODS: The NACI Meningococcal Disease Working Group developed a predefined search strategy to identify all eligible studies, assessed the quality of these studies, and summarized and analyzed the findings. According to the NACI evidence-based process, the working group then proposed recommendations and identified the grade of evidence that supported them. In light of the evidence, the recommendations were then considered and approved by NACI. RESULTS: The two serogroup B meningococcal vaccines currently authorized for use in Canada are not interchangeable as they contain different antigens and there are no published studies on the immunogenicity resulting from a vaccination series combining the two products. Following the review of evidence, NACI recommends that MenB-fHBP vaccine may be considered as an option for use in individuals 10 years of age and older in situations when a serogroup B meningococcal vaccine should be offered: 1) during serogroup B meningococcal disease outbreaks or with the emergence of hyperendemic N. meningitidis strains that are predicted to be susceptible to the vaccine; 2) for individuals who are close contacts with a case of invasive meningococcal disease caused by serogroup B N. meningitidis; 3) for individuals with underlying medical conditions that would put them at higher risk of meningococcal disease than the general population; or 4) for individuals at higher risk of exposure to serogroup B meningococcal isolates than the general population. NACI also recommends that MenB-fHBP vaccine may be considered as an option for individuals 10-25 years of age who are not at higher risk of meningococcal disease than the general population, but who wish to reduce their risk of invasive serogroup B meningococcal disease. CONCLUSION: NACI recommends immunization against serogroup B IMD for all individuals who are at a higher risk of disease due to an underlying medical condition or an increased risk of exposure. In addition to providing guidance to public health decision-makers (i.e. provinces/territories making decisions for publicly-funded immunization programs), these NACI recommendations provide information to individuals, vaccine providers and organizations about vaccines that may not currently be included in publicly funded immunization programs. NACI continues to recommend against the use of the serogroup B vaccines in routine universal immunization programs in Canada at this time.

Effect of increasing the delivery of smoking cessation care in alcohol and other drug treatment centres: a cluster-randomized controlled trial.

AIM: Aims were to test the effectiveness of an organizational change intervention integrating smoking cessation treatment into usual alcohol and other drug (AOD) treatment, compared with usual care, on (1) 7-day point prevalence abstinence (PPA) at 8 weeks follow-up; (2) prolonged abstinence; (3) cigarettes smoked per day; (4) number of quit attempts; and (5) offer and use of nicotine replacement therapy (NRT). All outcomes were assessed at 8 weeks and 6.5 months follow-up. DESIGN: Cluster-randomized controlled trial, with AOD service as unit of randomization, conducted January 2015-March 2016. SETTING: Thirty-two eligible services (provided face-to-face client sessions to ≥ 50 clients/year) in Australia were randomized to control (usual care; n = 15) or intervention (n = 17) groups by an independent blinded biostatistician. PARTICIPANTS: Eligible participants (≥ 16 years, current smoker) completed surveys at the service at baseline (n = 896) and telephone follow-up surveys (conducted by blinded assessors) at 8 weeks (n = 471; 53%) and 6.5 months (n = 427; 48%). INTERVENTION: Intervention services received an intervention to establish routine screening, assessment and delivery of smoking cessation care. MEASUREMENTS: Primary outcome was biochemically verified 7-day PPA at 8-week follow-up. Secondary outcomes included verified and self-reported prolonged abstinence, self-reported 7-day PPA, cigarettes/day, quit attempts and offer and use of NRT. Intention-to-treat analyses were performed, assuming missing participants were not abstinent. FINDINGS: At 8 weeks, the findings in verified 7-day PPA between groups [2.6 versus 1.8%, odds ratio (OR) = 1.72, 95% confidence interval (CI) = 0.5-5.7, P = 0.373] were inconclusive as to whether a difference was present. Significantly lower mean cigarettes/day were reported in the intervention group compared to the usual care group at 8 weeks [incidence rate ratio (IRR) = 0.88, 95% CI = 0.8-0.95, P = 0.001] but were similar at 6.5 months (IRR = 0.96, 95% CI = 0.9-1.02, P = 0.240) follow-up. At both follow-ups the intervention group reported higher rates of NRT use. CONCLUSIONS: Integrating smoking cessation treatment into addiction services did not significantly improve short-term abstinence from smoking.

Predominantly Antibody-Deficient Patients With Non-infectious Complications Have Reduced Naive B, Treg, Th17, and Tfh17 Cells.

Background: Patients with predominantly antibody deficiency (PAD) suffer from severe and recurrent infections that require lifelong immunoglobulin replacement and prophylactic antibiotic treatment. Disease incidence is estimated to be 1:25,000 worldwide, and up to 68% of patients develop non-infectious complications (NIC) including autoimmunity, which are difficult to treat, causing high morbidity, and early mortality. Currently, the etiology of NIC is unknown, and there are no diagnostic and prognostic markers to identify patients at risk. Objectives: To identify immune cell markers that associate with NIC in PAD patients. Methods: We developed a standardized 11-color flow cytometry panel that was utilized for in-depth analysis of B and T cells in 62 adult PAD patients and 59 age-matched controls. Results: Nine males had mutations in Bruton's tyrosine kinase (BTK) and were defined as having X-linked agammaglobulinemia. The remaining 53 patients were not genetically defined and were clinically diagnosed with agammaglobulinemia (n = 1), common variable immunodeficiency (CVID) (n = 32), hypogammaglobulinemia (n = 13), IgG subclass deficiency (n = 1), and specific polysaccharide antibody deficiency (n = 6). Of the 53, 30 (57%) had one or more NICs, 24 patients had reduced B-cell numbers, and 17 had reduced T-cell numbers. Both PAD-NIC and PAD+NIC groups had significantly reduced Ig class-switched memory B cells and naive CD4 and CD8 T-cell numbers. Naive and IgM memory B cells, Treg, Th17, and Tfh17 cells were specifically reduced in the PAD+NIC group. CD21lo B cells and Tfh cells were increased in frequencies, but not in absolute numbers in PAD+NIC. Conclusion: The previously reported increased frequencies of CD21lo B cells and Tfh cells are the indirect result of reduced naive B-cell and T-cell numbers. Hence, correct interpretation of immunophenotyping of immunodeficiencies is critically dependent on absolute cell counts. Finally, the defects in naive B- and T-cell numbers suggest a mild combined immunodeficiency in PAD patients with NIC. Together with the reductions in Th17, Treg, and Tfh17 numbers, these key differences could be utilized as biomarkers to support definitive diagnosis and to predict for disease progression.

Quantification of T-Cell and B-Cell Replication History in Aging, Immunodeficiency, and Newborn Screening.

Quantification of T-cell receptor excision circles (TRECs) has impacted on human T-cell research, but interpretations on T-cell replication have been limited due to the lack of a genomic coding joint. We here overcome this limitation with multiplex TRG rearrangement quantification (detecting ~0.98 alleles per TCRαß+ T cell) and the HSB-2 cell line with a retrovirally introduced TREC construct. We uncovered <5 cell divisions in naive and >10 cell divisions in effector memory T-cell subsets. Furthermore, we show that TREC dilution with age in healthy adults results mainly from increased T cell replication history. This proliferation was significantly increased in patients with predominantly antibody deficiency. Finally, Guthrie cards of neonates with Down syndrome have fewer T and B cells than controls, with similar T-cell and slightly higher B-cell replication. Thus, combined analysis of TRG coding joints and TREC signal joints can be utilized to quantify in vivo T-cell replication, and has direct applications for research into aging, immunodeficiency, and newborn screening.