Evaluating patient immunocompetence through antibody response to pneumococcal polysaccharide vaccine using a newly developed 23 serotype multiplexed assay.

Assessing T-cell independent antibody response to polysaccharide vaccines is crucial for diagnosing humoral immune deficiencies. However, immunocompetence criteria based on S. pneumoniae vaccination remain unclear. We evaluated IgG antibody vaccine response in healthy individuals to establish interpretive criteria. Pre- and 4-week post-vaccination sera were collected from 79 adults. Antibody concentrations to PNEUMOVAX 23 serotypes were measured using a multiplexed platform. Immunocompetence was determined by fold increase in post-vaccination response, percentage of serotypes achieving 4- or 2-fold antibody ratio, and post-vaccination concentration ≥ 1.3 µg/mL. Immunogenicity varied widely across the 23 serotypes (26.6% to 94.9% for ≥4-fold increase, 51.9% to 98.7% for ≥2-fold increase). Immunocompetence based on historic criteria of ≥4-fold increase in antibody ratio to ≥70% of serotypes was low (72.2%), but increased to 98.7% with criteria of at least a 2-fold increase and/or post-vaccination concentration ≥ 1.3 µg/mL. Current criteria for assessing immunocompetence may be overly stringent and require updating.

Psychiatrists can save lives with naloxone.

OBJECTIVES: Naloxone is an effective medication used to reverse opioid overdoses. Distributing naloxone directly to those at risk, therefore, reduces the risk of opioid-related deaths. New legislation in Australia means a prescription is no longer required to access naloxone. Whilst acknowledging the benefits of increased access, we aim to evaluate the impact psychiatrists can have on naloxone provision due to their unique position as doctors often working with those who may be at risk. METHODS: Data was recorded on those accessing naloxone from a co-located addiction and mental health service. Descriptive statistics were generated to establish the cohort characteristics, prior knowledge of naloxone and outcome of previously supplied naloxone. RESULTS: Naloxone was dispensed 488 times from 2021 to 2023. 267 people had previously been prescribed naloxone from these sites where 137 (51.3%) were reportedly used in an opioid reversal. CONCLUSIONS: Our findings highlight the importance of community access to naloxone in reducing opioid-related harm. Whilst removing the need for a prescription makes naloxone more accessible, it remains vital that doctors remain involved in this process to broaden the reach of supply to those at risk.

The cost-effectiveness of risk-stratified breast cancer screening in the UK.

BACKGROUND: There has been growing interest in the UK and internationally of risk-stratified breast screening whereby individualised risk assessment may inform screening frequency, starting age, screening instrument used, or even decisions not to screen. This study evaluates the cost-effectiveness of eight proposals for risk-stratified screening regimens compared to both the current UK screening programme and no national screening. METHODS: A person-level microsimulation model was developed to estimate health-related quality of life, cancer survival and NHS costs over the lifetime of the female population eligible for screening in the UK. RESULTS: Compared with both the current screening programme and no screening, risk-stratified regimens generated additional costs and QALYs, and had a larger net health benefit. The likelihood of the current screening programme being the optimal scenario was less than 1%. No screening amongst the lowest risk group, and triannual, biennial and annual screening amongst the three higher risk groups was the optimal screening strategy from those evaluated. CONCLUSIONS: We found that risk-stratified breast cancer screening has the potential to be beneficial for women at the population level, but the net health benefit will depend on the particular risk-based strategy.

Reduced quantity and function of pneumococcal antibodies are associated with exacerbations of COPD in SPIROMICS.

While hypogammaglobulinemia is associated with COPD exacerbations, it is unknown whether frequent exacerbators have specific defects in antibody production/function. We hypothesized that reduced quantity/function of serum pneumococcal antibodies correlate with exacerbation risk in the SPIROMICS cohort. We measured total pneumococcal IgG in n = 764 previously vaccinated participants with COPD. In a propensity-matched subset of n = 200 with vaccination within five years (n = 50 without exacerbations in the previous year; n = 75 with one, n = 75 with ≥2), we measured pneumococcal IgG for 23 individual serotypes, and pneumococcal antibody function for 4 serotypes. Higher total pneumococcal IgG, serotype-specific IgG (17/23 serotypes), and antibody function (3/4 serotypes) were independently associated with fewer prior exacerbations. Higher pneumococcal IgG (5/23 serotypes) predicted lower exacerbation risk in the following year. Pneumococcal antibodies are inversely associated with exacerbations, supporting the presence of immune defects in frequent exacerbators. With further study, pneumococcal antibodies may be useful biomarkers for immune dysfunction in COPD.

Addiction experts: The discrepancy between expectations and reality of generalist psychiatry training.

OBJECTIVE: The generalist psychiatrist is recognised in Australia as a specialist in the management of addiction. However, generalist training does not adequately prepare psychiatrists to take on this expert role. This problem is exacerbated by the lack of consensus around core competencies and training pathways. This article conceptualises the status of addiction training in generalist psychiatry training, outlines current gaps and worrying trends and provides suggestions for how these can be addressed. CONCLUSION: Limited international leadership in the field provides an opportunity for psychiatry training in Australia and New Zealand to set a gold standard for training general psychiatrists to hold core competencies in addiction psychiatry. Key strategies will include: the identification and monitoring of addiction rotations; providing a formal training module in addiction; specifying a set proportion of addiction exam questions; and obtain consensus on core competencies.

An enzyme-linked immunospot assay to evaluate Pneumovax response when on intravenous immunoglobulin.

BACKGROUND: Testing for common variable immunodeficiency (CVID) requires evaluation of specific antibody responses to vaccines. Current practice of evaluating pneumococcal serotype-specific immunoglobulin (Ig)G levels after Pneumovax (P23) has several limitations and is not accurate for patients already on immunoglobulin replacement. In contrast, the enzyme-linked immunospot (ELISPOT) assay can be interpreted in patients on immunoglobulin replacement as ex vivo measurement of specific antibody-secreting cells (ASCs). OBJECTIVE: To optimize and test an ELISPOT assay to evaluate vaccination response to P23 and compare with P23 serotype-specific IgG for patients on intravenous immunoglobulin (IVIG). METHODS: We prospectively enrolled a total of 15 adults: normal controls (n = 8), patients with CVID on IVIG replacement (n = 2), patients on IVIG replacement for recurrent infections who did not meet diagnostic criteria for CVID, considered IgG deficiency (n = 2), and patients without immunodeficiency on high-dose IVIG for other diagnosis (n = 3). We measured P23 serotype-specific IgG before and 4 weeks after P23 and ELISPOT ASCs before and 1 week after P23 (with B-cell subpopulation analysis by flow cytometry in patients on IVIG). RESULTS: Normal controls had a vaccination response by P23 serotype-specific IgG, whereas patients on IVIG did not. Except for true patients with CVID on IVIG, a P23 ELISPOT ASC response was found in normal controls (highest) and most patients on IVIG for recurrent infections or other diagnosis. CONCLUSION: Our pilot study suggests that an optimized ELISPOT protocol has utility to evaluate the P23-specific antibody response after vaccination. Our ELISPOT assay seemed reliable for patients on IVIG and may help differentiate true patients with CVID from those with a less stringent diagnosis while on IVIG.

Clinical significance of measuring serum cytokine levels as inflammatory biomarkers in adult and pediatric COVID-19 cases: A review.

Coronavirus disease 2019 (COVID-19) is a rapidly evolving infectious/inflammatory disorder which has turned into a global pandemic. With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as its etiologic agent, severe COVID-19 cases usually develop uncontrolled inflammatory responses and cytokine storm-like syndromes. Measuring serum levels of pro-inflammatory cytokines (e.g., IL-6 and others) as inflammatory biomarkers may have several potential applications in the management of COVID-19, including risk assessment, monitoring of disease progression, determination of prognosis, selection of therapy and prediction of response to treatment.This is especially true for pediatric patients with COVID-19 associated Kawasaki-like disease and similar syndromes. In this report, we review the current knowledge of COVID-19 associated cytokines, their roles in host immune and inflammatory responses, the clinical significance and utility of cytokine immunoassays in adult and pediatric COVID-19 patients, as well as the challenges and pitfalls in implementation and interpretation of cytokine immunoassays. Given that cytokines are implicated in different immunological disorders and diseases, it is challenging to interpret the multiplex cytokine data for COVID-19 patients. Also, it should be taken into consideration that biological and technical variables may affect the commutability of cytokine immunoassays and enhance complexity of cytokine immunoassay interpretation. It is recommended that the same method, platform and laboratory should be used when monitoring differences in cytokine levels between groups of individuals or for the same individual over time. It may be important to correlate cytokine profiling data with the SARS-CoV-2 nucleic acid amplification testing and imaging observations to make an accurate interpretation of the inflammatory status and disease progression in COVID-19 patients.

How can we decide a fair allocation of healthcare resources during a pandemic?

Whenever the government makes medical resource allocation choices, there will be opportunity costs associated with those choices: some patients will have treatment and live longer, while a different group of patients will die prematurely. Because of this, we have to make sure that the benefits we get from investing in treatment A are large enough to justify the benefits forgone from not investing in the next best alternative, treatment B. There has been an increase in spending and reallocation of resources during the COVID-19 pandemic that may have been warranted given the urgency of the situation. However, these actions do not bypass the opportunity cost principle although they can appear to in the short term, since spending increases cannot continue indefinitely and there are patient groups who lose out when resources are redirected to pandemic services. Therefore, policy-makers must consider who bears the cost of the displaced healthcare resources. Failure to do so runs a risk of reducing overall population health while disproportionally worsening health in socially disadvantaged groups. We give the example of ethnic minorities in England who already had the worst health and, due to structural injustices, were hardest hit by the pandemic and may stand to lose the most when services are reallocated to meet the resource demands of the crisis. How can we prevent this form of health inequity? Our proposal is forward-looking: we suggest that the government should invest our resources wisely while taking issues of equity into account-that is, introduce cost-equity analysis.

An eReferral Management & Triage System for minor Oral surgery referrals from primary care dentists: a cost-effectiveness evaluation.

OBJECTIVE: Oral surgery referrals from NHS dental practices are rising, increasing the pressures on available hospital resources. We assess if an electronic referral system with consultant or peer (general dental practitioner) led triage of patient referrals from general dental practices can effectively divert patients requiring minor oral surgery into specialist led primary care settings at a reduced cost whilst providing care of the same or enhanced quality. One year of no triage (all referrals treated in secondary care) was followed by one-year of consultant led triage, which in turn was followed by year of peer-led triage. METHOD: A health economic evaluation of all patient referrals from 27 UK dental practices for oral surgery procedures. The follow-up is over a three-year period at hospital dental services in two general hospitals, one dental hospital, and a single specialist oral surgeon based in two primary care practices. The evaluation is a comparison of mean outcomes in the hospitals and in specialist primary care dental services between the study periods (i.e. periods with and without the triage system). The main outcomes of interest are mean NHS cost saving per referral (costs to the NHS and costs to broader society), proportion of diverted referrals, case-mix of referrals and patient reports of the quality of dentistry services received at their referral destination. RESULTS: The proportion of referrals diverted to specialist primary care was similar during both periods (45% under consultant-led triage and 43% under GDP-led triage). Statistically significant savings per referral diverted were found (£116.11 under consultant-led triage, £90.25 under GDP-led triage). There were no statistically significant changes in the case-mix of referrals. Cost savings varied according to the coding (and hence tariff) of referred cases by the provider hospitals. Patients reported similarly high levels of satisfaction scores for treatment in specialist primary care and secondary care settings. CONCLUSIONS: Implementation of electronic referral management in primary care, when combined with triage, led to appropriate diversions to specialist primary care. Although cost savings were realised by referral diversion these savings are dependent on the particular tariff allocation (coding) practices of provider hospitals.

Completing the RANZCP scholarly project in a rural/regional setting: a practical example.

OBJECTIVE: The Royal Australian and New Zealand College of Psychiatrists (RANZCP) scholarly project (SP) is a major hurdle for trainees completing psychiatric training - intensified for those working in rural settings. Whilst strategies to overcome this challenge have been proposed, there are few examples of how these have been successfully implemented. This report will describe the completion of a RANZCP SP in a regional setting, with supervision and support provided by an academic psychiatrist working within a metropolitan research centre. CONCLUSION: Trainees in remote geographical locations can utilise expert supervision from academic psychiatrists to successfully complete the SP. Key components are support from both the trainee and supervisor's employers, utilisation of a range of supervision modalities and a clear pragmatic memorandum of understanding between the supervisor and trainee. This initiative had widespread benefits beyond completion of the SP for all parties involved.

Addiction psychiatry training in rural Australia: a Victorian initiative.

OBJECTIVE: The shortage of addiction psychiatrists in Australia results in poor access to specialist care. This is most evident in rural Australia, a population experiencing significant issues related to drugs, alcohol and mental illness. This problem is exacerbated by the lack of addiction psychiatry training in rural Australia. Purposeful and well-coordinated educational opportunities for health professionals in rural settings can assist in recruitment and retention. This report will describe the establishment of an addiction psychiatry training programme in regional Victoria. CONCLUSION: Rural addiction psychiatry training programmes that ensure trainees meet the competencies required of an addiction psychiatrist can be established. Key components in establishing programmes are: collaboration between a breadth of local services; provision of quality supervision; support of the Royal Australian and New Zealand College of Psychiatrists (RANZCP), senior psychiatrists and managers; provision of assistance to trainees and their families; and appropriate selection of trainees.

A Review of the Methods Used to Generate Utility Values in NICE Technology Assessments for Children and Adolescents.

OBJECTIVE: This review summarizes and critically examines methods used to generate utilities for child and adolescent health states in previous National Institute for Health and Care Excellence (NICE) technology assessments (TA) and highly specialized technology (HST) evaluations. METHODS: We identified all NICE TA and HST evaluations in which the licensed indication for the technology included people younger than 18 and included in the review all evaluations using a cost-utility analysis. RESULTS: The review includes 40 TA and HST evaluations. Most assessments generated utility values with the EQ-5D scored using the adult version of the EQ-5D either exclusively (n = 16) or alongside other utility measures and direct elicitation methods of patient own utility (n = 17), although 7 did not use the EQ-5D. Eight assessments used both the EQ-5D child- and adolescent-specific preference-based measures: Health Utilities Index Mark 2 (n = 6), child- and adolescent-specific preference-based measure for atopic dermatitis (n = 1), and youth version of the EQ-5D (EQ-5D-Y) valued using the adult EQ-5D value set (n = 1) or generated using mapping and valued using the adult EQ-5D value set (n = 2). Some cost-utility analyses used age adjustment (utility subtractions, weights, and published mapping formulae) from the adult EQ-5D UK population norms to reflect the general population or disease-free health for children and adolescents (n = 9), and 1 assessment assumed full health (utility value of 1). CONCLUSION: The review found limited use of child and adolescent population-specific measures to generate health state utility values for children and adolescents in NICE technology assessments. Often assessments involve the use of an adult-specific measure to reflect the health of children.

Are Current Reporting Standards Used to Describe Health State Utilities in Cost-Effectiveness Models Satisfactory?

OBJECTIVE: The aims of this study were to examine current reporting standards of health state utilities (HSU) using a review of published cost-effectiveness analyses in cardiovascular disease and to explore the impact of variation in model inputs used in these on estimated quality-adjusted life-years (QALYs) and cost-effectiveness. METHODS: Key health/economics bibliographic databases were searched to identify relevant articles published after 2014. Any narrative or values relating to the HSU used in the model were extracted and reviewed. The HSUs were systematically applied to an existing model to explore the influence of different values on QALYs and the incremental cost-effectiveness ratio. RESULTS: Twenty-four peer-reviewed articles were identified. Only 2 studies referred to a literature review for the HSUs. Most (18 of 24) referenced previously published economic studies (as opposed to the original source) for at least 1 of the HSUs. Only 4 studies referenced the original sources and reported all of the HSUs accurately, and several did not provide all the HSUs. Little information was provided on the methods used to calculate QALYs, for example, the duration of time for acute HSUs, what the baseline HSU was, the method that was used to assign HSUs for subsequent different events, or how constant HSUs for clinical events were combined with age-adjusted baseline values. The huge differences in HSUs used in the studies produced substantial variations in the QALYs and incremental cost-effectiveness ratios generated from the cost-effectiveness model. CONCLUSION: Current standards are poor, and there is a need for greater transparency in reporting the HSUs used in cost-effectiveness models.

Is it time to include people with intellectual disabilities in Royal Australian and New Zealand College of Psychiatrists' treatment guidelines?

OBJECTIVE: The Royal Australian and New Zealand College of Psychiatrists' (RANZCP) treatment guidelines set the zeitgeist for psychiatric practice in Australasia. This review conceptualises the current approach to treatment of individuals with an intellectual disability and co-occurring mental illness in RANZCP guidelines, and its potential impact. CONCLUSIONS: The enduring omission of people with an intellectual disability and co-occurring mental illness from RANZCP clinical guidelines is a missed opportunity in normalising care and optimising outcomes for people with an intellectual disability. There are substantial cultural, political and historical overlays contributing to the ongoing divide between health and disability. In developing psychiatric guidelines, authors should consider including people with co-occurring intellectual disability as a specific population, that requires distinctive consideration.

Does capitation affect the delivery of oral healthcare and access to services? Evidence from a pilot contact in Northern Ireland.

BACKGROUND: In May 2009, the Northern Ireland government introduced General Dental Services (GDS) contracts based on capitation in dental practices newly set up by a corporate dental provider to promote access to dental care in populations that had previously struggled to secure service provision. Dental service provision forms an important component of general health services for the population, but the implications of health system financing on care delivered and the financial cost of services has received relatively little attention in the research literature. The aim of this study is to evaluate the policy effect capitation payment in recently started corporate practices had on the delivery of primary oral healthcare in Northern Ireland and access to services. METHODS: We analysed the policy initiative in Northern Ireland as a natural experiment to find the impact on healthcare delivery of the newly set up corporate practices that use a prospective capitation system to remunerate primary care dentists. Data was collected from GDS claim forms submitted to the Business Services Organisation (BSO) between April 2011 and October 2014. Health and Social Care Board (HSCB) practices operating within a capitation system were matched to a control group, who were remunerated using a retrospective fee-for-service system. RESULTS: No evidence of patient selection was found in the HSCB practices set up by a corporate provider and operated under capitation. However, patients were less likely to visit the dentist and received less treatment when they did attend, compared to those belonging to the control group (P < 0.05). The extent of preventive activity offered and the patient payment charge revenue did not differ between the two practice groups. CONCLUSION: Although remunerating NHS primary care dentists in newly set up corporate practices using a prospective capitation system managed costs within healthcare, there is evidence that this policy may have reduced access to care of registered patients.