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Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Different from developed countries, there is a paucity of research examining how the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets relate to lipids in less-developed ethnic minority regions (LEMR). A total of 83 081 participants from seven ethnic groups were retrieved from the baseline data of the China Multi-Ethnic Cohort study, which was conducted in less-developed Southwest China between May 2018 and September 2019. Multivariable linear regression models were then used to examine the associations of the DASH and alternative Mediterranean diet (AMED) scores, assessed by modified DASH score and AMED, as well as their components with total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, TAG and TC/HDL-cholesterol. The DASH scores were negatively associated with TC, HDL-cholesterol and TAG. Comparing the highest quintiles with the lowest DASH scores, TC decreased 0·0708 (95 % CI −0·0923, −0·0493) mmol/l, HDL-cholesterol decreased 0·0380 (95 % CI −0·0462, −0·0299) mmol/l and TAG decreased 0·0668 (95 % CI −0·0994, −0·0341) mmol/l. The AMED scores were negatively associated with TC, LDL-cholesterol and HDL-cholesterol. Comparing the highest quintiles with the lowest AMED scores, TC decreased 0·0816 (95 % CI −0·1035, −0·0597) mmol/l, LDL-cholesterol decreased 0·0297 (95 % CI −0·0477, −0·0118) mmol/l and HDL-cholesterol decreased 0·0275 (95 % CI −0·0358, −0·0192) mmol/l. Although both the DASH diet and the Mediterranean diet were negatively associated with blood lipids, those associations showed different patterns in LEMR, particularly for TAG and HDL-cholesterol.
This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China.
This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10–20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used.
There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures.
The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.
Teenagers are important carriers of Neisseria meningitidis, which is a leading cause of invasive meningococcal disease. In China, the carriage rate and risk factors among teenagers are unclear. The present study presents a retrospective analysis of epidemiological data for N. meningitidis carriage from 2013 to 2017 in Suizhou city, China. The carriage rates were 3.26%, 2.22%, 3.33%, 3.53% and 9.88% for 2013, 2014, 2015, 2016 and 2017, respectively. From 2014 to 2017, the carriage rate in the 15- to 19-year-old age group (teenagers) was the highest and significantly higher than that in remain age groups. Subsequently, a larger scale survey (December 2017) for carriage rate and relative risk factors (population density, time spent in the classroom, gender and antibiotics use) were investigated on the teenagers (15- to 19-year-old age) at the same school. The carriage rate was still high at 33.48% (223/663) and varied greatly from 6.56% to 52.94% in a different class. Population density of the classroom was found to be a significant risk factor for carriage, and 1.4 persons/m2 is recommended as the maximum classroom density. Further, higher male gender ratio and more time spent in the classroom were also significantly associated with higher carriage. Finally, antibiotic use was associated with a significantly lower carriage rate. All the results imply that attention should be paid to the teenagers and various measures can be taken to reduce the N. meningitidis carriage, to prevent and control the outbreak of IMD.
Despite widespread use of oxygen (O2) therapy, there is relatively little available information on routine O2 administration and monitoring; this is an issue particularly when considering the potential risks associated with inappropriate O2 utilization. A rapid health technology assessment (HTA) was conducted to inform the Respiratory Health Strategic Clinical Network Oxygen Summit in Alberta on aspects related to current practice in the use of O2 therapy in acute care, including administration, safety and quality, and inappropriate practice. Clinical audit is a tool used to determine deviations in practice and to identify opportunities for improvement. The objective of this presentation is to describe the experience and lessons learned from including clinical audit studies in the rapid HTA.
A standardized rapid review approach was used to identify, select, and synthesize evidence from studies published in English from 2005 to 2016. A supplementary literature search conducted in 2018 provided additional background information on the value, applicability, and limitation of using results from clinical audit studies to inform questions of good practice.
Twenty-four clinical audit studies on O2 therapy were identified; the majority were conducted in the United Kingdom. The studies varied in design, methodology, and data and outcomes reporting. Ten studies investigated the appropriateness of O2 therapy prescription pre- and post-implementation of local initiatives and interventions, which helped pinpoint major gaps in current practice, and identified general recommendations for improvement of practice. A list of reporting criteria is proposed for improving the reporting of clinical audit studies results.
Conducting clinical audit studies is resource-intensive. In the absence of other research evidence and local practice data, translating results from clinical audit studies conducted in other jurisdictions, while challenging, can help address appropriateness questions. However, inferences from these studies may be suitable only for certain topics or an operating context.
Due to an aging population, shortage of healthcare staff, and escalating healthcare costs, there has been a recent shift in the professional roles and responsibilities in acute care settings to help bridge the care gap. Paramedics, whose primary responsibilities have been in emergency/transportation services, are increasingly involved in the management of chronic diseases in the community setting. However, even with additional training, there are concerns about the safety and effectiveness of this expanded role. The objective of this presentation is to highlight some of the key findings from a health technology assessment report on the safety and effectiveness of community paramedicine in assessing and managing conditions/diseases with low acuity.
A systematic review was conducted to identify studies that evaluated the safety and effectiveness of different community paramedicine programs.
Four systematic reviews and 20 primary studies (one randomized controlled trial (RCT) and 19 observational studies) were identified. Of these, two systematic reviews and 14 primary studies focused on the safety and effectiveness of Emergency Care Practitioner (ECP) programs ̶ widely implemented programs whereby a paramedic or nurse undertakes activities traditionally performed by physicians, such as the initial assessment of patients, provision of simple treatment, or referral of patients to other clinical care. Limited evidence showed that ECP programs are promising in reducing repeated emergency calls, emergency department visits, hospital admissions/readmissions, and emergency transport charges. While the majority of included studies did not report any safety outcomes, no significant safety issues were identified from the cluster RCT. Evidence for other types of community paramedicine is limited.
Evaluation of the impact of community paramedicine programs remains methodologically challenging. Additional cluster RCTs may help determine the effectiveness of community paramedicine programs; safety outcomes should be a key element of future observational studies.
Conventional wisdom suggests that accelerating the speed of cancer diagnosis should improve health outcomes. However, cancer diagnosis requires complex coordination and effective communication between care providers working across many areas of the healthcare system. Since 2000, several nations and jurisdictions have aimed to improve timeliness of cancer diagnosis by integrating and coordinating cancer diagnostic services for patients. The objective of this study was to describe the impact of these existing initiatives.
We conducted an environmental scan consisting of a literature review (published academic and grey literature) and key informant consultations (online surveys and telephone interviews with experts who have knowledge of existing initiatives). We searched for initiatives in the United Kingdom, the Nordic countries, Canada, Australia, and New Zealand. For each initiative, we extracted data on their development and implementation, structure and functioning, intended outcomes and effectiveness, costs and cost savings, and enablers and barriers.
Eighty-nine relevant documents and 20 key informants contributed to this study. We identified 21 relevant initiatives, including seven national initiatives targeting multiple types of cancer. The literature review found that most initiatives accelerated the diagnostic phase of cancer care by several days or weeks. These wait time reductions were often associated with improved patient experience, but not less advanced cancer stage or increased long-term survival. Insights from key informants improved our understanding of the costs, enablers, and barriers associated with program implementation and maintenance.
These results can be used as a first step to inform the development, evaluation, and improvement of international cancer diagnostic pathways. Stakeholders wishing to accelerate cancer diagnosis should consider the feasibility of achieving their intended program outcomes based on the existing research evidence, desired type of initiative, and jurisdiction's unique contextual factors.
The objectives of this study were to systematically review published research on the relationship between nursing staff coverage, care hours, and quality of care (QoC) in long-term care (LTC) facilities; and to conduct a real world evidence (RWE) analysis using Alberta real world data (RWD) to inform policy makers on whether any amendments could be made to current regulations.
A systematic review (SR) of research evidence published between January 2000 and May 2018 on the relationship between nursing staff coverage, care hours, and QoC in LTC facilities was conducted. Panel data regressions using available RWD from Alberta, Canada, were performed to assess associations between nursing care hours and LTC outcomes. Outcomes of interest included quality indicators related to resident outcomes, hospital admissions, emergency room visits and family satisfaction. Nursing care hours considered in SR and RWE analysis included those provided by registered nurses (RNs) and licensed practical nurses (LPNs).
The SR found inconsistent and poor quality evidence relevant to the questions of interest, indicating a great uncertainty about the association between nursing staff time and type of coverage and QoC. Although some positive indications were suggested, major weaknesses of reviewed studies limited interpretation of SR results. RWE analysis found that impact of care hours on LTC outcomes was heterogeneous, dependent on outcome measurements. There was evidence that total staff, RN, and LPN hours had positive effects on some resident outcomes and magnitude of effect differed for different nursing staff.
No definitive conclusion could be drawn on whether changing nursing staff time or nursing staff coverage models would affect residents’ outcomes based on the research evidence gathered in the SR. RWE analysis helped to fill a gap in the available published literature and allowed policy makers to better understand the impact of revising current regulations based on actual outcomes.
Environmental scan reports, usually consisting of literature reviews and/or key informant consultations (such as online surveys or personal interviews), broadly describe the current local, national, and international landscape surrounding health care practices, programs, or the use of technologies. Funding agencies and health organizations recognize environmental scans as a valuable way to inform decision-makers about the context, practice variations, and knowledge gaps surrounding a topic. Despite their increasing popularity in health technology assessment (HTA), there is limited guidance available for conducting environmental scans, variation in methods used across and within HTA agencies, and lack of consensus on an appropriate definition, purpose, and process.
We conducted an informal literature review and consulted experienced researchers from other HTA agencies to identify existing methods guidance for conducting environmental scans. We then adapted these methods to conduct an environmental scan of initiatives to accelerate cancer diagnosis.
There was limited and vague guidance on the definition, purpose, and process of conducting environmental scans in the context of HTA. This introduced challenges but provided the flexibility to modify our approach to meet requestor needs. Our environmental scan included: (i) a literature review, to identify and describe relevant initiatives and to locate data on effectiveness (which is often out-of-scope for environmental scans but was of priority to the requestor); (ii) stakeholder surveys, which helped “fill in the gaps” of the literature review and helped locate additional initiatives; and (iii) targeted key informant interviews, which provided rich follow-up data on the initiatives most important to the requestor.
By describing our experiences adapting limited methods guidance to meet requestor needs, we hope to contribute to the evolving discussion about the definition, purpose, and process of environmental scans to inform health policy decision-making. We will reflect on challenges encountered, potential solutions, and lessons learned, and will discuss ongoing areas of methodological uncertainty.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.
This article retrospectively examines the evolution of rapid assessments (RAs) produced by the Health Technology Assessment (HTA) Program at the Institute of Health Economics over its 25-year relationship with a single requester, the Alberta Health Ministry (AHM).
The number, types, and methodological attributes of RAs produced over the past 25 years were reviewed. The reasons for developmental changes in RA processes and products over time were charted to document the push–pull tension between AHM needs and the HTA Program's drive to meet those needs while responding to changing methodological benchmarks.
The review demonstrated the dynamic relationship required for HTA researchers to meet requester needs while adhering to good HTA practice. The longstanding symbiotic relationship between the HTA Program and the AHM initially led to increased diversity in RA types, followed by controlled extinction of the less fit (useful) “transition species.” Adaptations in RA methodology were mainly driven by changes in best practice standards, requester needs, the healthcare environment, and staff expertise and technology.
RAs are a useful component of HTA programs. To remain relevant and useful, RAs need to evolve according to need within the constraints of HTA best practice.
The Health Technology Assessment (HTA) Program at the Institute of Health Economics (IHE) has conducted rapid assessments (RAs) for 25 years. The presentation draws on this experience to chart the evolution of RAs over a 25-year relationship between a policy maker and an arms-length HTA agency to quantify the effects of this partnership on the RAs produced.
The number, types, and methodological attributes of RAs produced over a 25-year partnership with a single requestor were reviewed. The reasons for developmental changes in RA products over time were charted to document the push-pull tension between requestor needs and HTA best practice. The elements contributing to the relevance and impact, or not, of the RAs were also identified.
Results demonstrated the dynamic relationship required for HTA researchers to meet best practice and requestor needs. As literature search spans lengthened and data analyses became more complex, limitations were imposed on RAs to fulfill the requirements of timeliness, utility, and best practice. Adaptations were driven by requestor, researcher, and the external policy environment. Facilitators of RA utility for HTA requestors include: asking focused, well-articulated questions; specifying the request's purpose; providing detailed information about local context and other relevant issues; and understanding the risk of bias associated with RAs. Considerations for HTA doers include: assembling a team using a triage process; involving requestors throughout RA development; negotiating deliverables and timelines using a HTA product matrix; transparently reporting methods; narratively describing methodological issues; and internally reviewing the draft RAs.
RAs are a useful component of HTA programs. To keep these products relevant and useful, HTA agencies must allow RAs to evolve according to need, but with grounding in good practice. Negotiating the line between rigor and relevance is a key skill for HTA agencies. Having the right team is helpful.
Population growth, epidemiological and demographic transition, and a shortage of healthcare workers are affecting health care systems in Australia, Canada, the United Kingdom (UK), and the United States (US). Community paramedicine (CP) programs provide a bridge between primary care and emergency care to address the needs of patients with low acuity but lack of access to primary care. However, how to capture the key characteristics of these programs and present them in a meaningful way is still a challenge. The objective of this presentation is to identify and describe the characteristics of currently existing CP programs in the four countries to inform policy-making on CP program development in Alberta.
Information was obtained from systematic reviews, health technology assessments, general reviews, and government documents identified through a comprehensive literature search. The characteristics of the CP programs are described using a framework originally developed in Australia with three categories: (i) the primary health care model, (ii) the health integration model (in Australia, called the substitution model), and (iii) the community coordination model.
In general, Australia emphasizes rural/remote paramedics, whereas Canada, the UK, and the US implement expanded paramedic practice within different environments including rural, remote, regional, and metropolitan settings. Extended care provider programs have been intensively investigated and widely implemented in the UK. While the identified CP programs vary in terms of program components, designation of providers, skill mix, target population, and funding model, the majority of these CP programs fall under the primary health care category of the Australian framework.
Transitioning from hospital-based to community-based health care requires careful consideration of all key factors that could contribute to future program success. Delineating key components of CP programs using the Australian framework will help Alberta decision-makers design, develop, and implement appropriate CP programs that adequately address local needs.
The cost-effectiveness of endovascular therapy (EVT) compared to tissue plasminogen activator (tPA) alone for acute ischemic stroke (AIS) has been established in the literature. However, decision-makers still face challenges of how to best deliver EVT in a timely manner to maximize patient outcomes while minimizing the burden to the healthcare system, given that AIS has time-dependent treatment outcomes. The objective of this presentation is to report an optimization approach for improving health system value and outcomes for patients with AIS who are eligible for EVT in Alberta.
An economic model was developed to compare combinations of “mothership” (transport directly to a comprehensive stroke center [CSC] to receive tPA and EVT) and “drip-and-ship” (transport to a primary stroke centre to receive tPA, followed by transport to a CSC to receive EVT) methods across Alberta. The model considered geographical variation and searched for the best delivery methods through a pairwise comparison of all possible strategies. The controlled variables including in the model were population densities, disease epidemiology, time/distance to hospitals, available medical services, treatment eligibility and efficacy, and costs. Patient outcomes were measured by functional independence. The model defined optimal strategies by identifying the transport methods that produced the highest probability of improved health outcomes at the lowest cost.
The analysis produced an optimization map showing optimal strategies for EVT delivery. The lifetime cost (standard deviation [SD]) per patient and likelihood (SD) of good outcomes was CAD 291,769 (CAD 11,576) [USD 226,207 (USD 8,975)] and 41.82 percent (0.013) when considering optimal clinical outcomes, and CAD 287,725 (CAD 4,141) [USD 223,097 (USD 3,211)] and 41.67 percent (0.016) when considering optimal economic efficiency.
Our model reduces the gap that exists between health technology implementation and cost-effectiveness analysis; namely, neither fully addresses relative efficiency driven by geographical variation, which may misrepresent system value in local settings. Implementation strategies generated in our model capture full values in terms of patient outcomes and costs.
Although individual patient data meta-analysis (IPD MA) is considered the gold standard of systematic reviews (SRs), a recent International Network of Agencies for Health Technology Assessment survey indicates that IPD MA is not frequently included in a health technology assessment (HTA), or conducted by HTA researchers. The objective of this presentation is to describe our first experience with including an IPD MA in a HTA report, discuss the added value for an evidence-based decision-making process, and advocate for expanding work in this field.
An overview of SRs on endovascular therapy for acute ischemic stroke included one IPD MA and six study-level SRs/MAs. Methodological quality was appraised by two reviewers independently using the tool recommended by the Cochrane IPD MA working group for the IPD MA, and the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) for the study-level reviews. Pooled results from subgroup analyses based on access to primary patient data were compared to those reported in SRs that conducted subgroup analyses based on the published data to identify patients or clinical factors that would impact clinical outcomes.
The overall findings were similar between the IPD MA and other SRs/MAs. However, when compared to aggregated data used in study-level SRs/MAs, subgroup analyses based on patient data allowed for adjustment of confounders, multiple categories within a subgroup, standardization of outcomes across trials, and detailed data checking. Larger sample sizes of each pre-defined subgroup permitted for more precise estimates of treatment effects. A number of methodological issues in the IPD MA were identified; particularly, no assessment of risk of bias of included trials was conducted.
Access to original patient data is demanding and conducting IPD MA requires extensive resources. The advantages of having an improved quality analysis, an appropriate quantification of the effects in the analyzed subgroups, and precision of results may justify additional efforts, and may increase confidence in the decision-making process.
A series of CoCrFeNiMox (x = 0.2, 0.4, 0.6, 0.8, 1.0, and 1.2) high-entropy alloys were designed to develop a eutectic high-entropy alloy system and to acquire a superfine eutectic structure. The results show that for the CoCrFeNiMox alloys, with the increase of Mo content from 0.2 to 1.2, the microstructures shift from a typical dendrite structure to a hypoeutectic microstructure (x = 0.6), and then to a fully eutectic microstructure (x = 0.8) with a lamellar spacing only 110 nm, and finally culminate in the hypereutectic structure (x = 1.0, x = 1.2). The XRD results show that CoCrFeNiMox alloys have a single FCC phase when x is 0.2 or 0.4. When Mo content is over 0.6, it begins to separate Cr9Mo21Ni20 intermetallic compounds. The hardness of the CoCrFeNiMox alloys is increasing significantly from 172.8 to 763.7 HV with the increase of Mo content. Meanwhile, the fracture strength increased but the ductility decreases. Among these alloys, the CoCrFeNiMo0.6 alloy shows excellent integrated mechanical properties of compressive fracture strength and strain, which are 2051 Mpa and 23%, respectively.
The characteristics and mechanism for unsteady shock train motions were experimentally studied in a constant-area rectangular duct. High-speed Schlieren techniques and high-frequency pressure measurements were utilized in this research. The results show that the shock train undergoes periodical motions in response to downstream periodical excitations. The mechanism for unsteady shock train motions is that the shock train keeps changing its moving speed to change the relative Mach number ahead of shock train to match the varying back-pressure condition. It can be found that the unsteady shock train motion can be predicted well with a theoretical model, which is based on this mechanism. A correlation between the amplitude of shock train motions and some flow parameters was illustrated using an analytical equation, which was confirmed by the experimental results.
To outline the methodological issues associated with the assessment of newborn screening for severe combined immunodeficiency, which was conducted to address the policy question of whether this test should be added to an existing newborn screening panel.
We conducted a systematic review of published primary studies and critically appraised the methodological quality of selected studies (1).
Fifteen studies were included; six focused on screening test performance, and seven on treatment effectiveness, and two on the effectiveness of a newborn screening program. The methodological issues identified included: (i) Overall poor methodological quality ratings of included studies using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). This tool was originally developed for assessing diagnostic accuracy studies where subjects usually receive both index test and reference standard so a 2×2 table can be constructed; however it is almost impossible to apply this cross-sectional approach to studies of a screening test for a rare disease like severe combined immunodeficiency. (ii) Case control design using healthy controls could inflate estimates of test accuracy compared to studies using a cohort of consecutive patients, possibly due to spectrum effects and limited-challenge bias. This type of study is useful in the early phase of test development, but estimates of test accuracy based on this type of study should be interpreted with caution. (iii) Some screening programs reported no false negatives, indicating a sensitivity of 100 percent. However, lack of a systematic search for “missed cases” created uncertainty in arriving at a true value for the sensitivity. (iv) Variations in inclusion of pre-term infants, races/ethnicities, and screening protocols made it difficult to compare screening test performance across different studies.
Although severe combined immunodeficiency screening was the first addition to the US Recommended Uniform Screening Panel following an evidence-based review process, caution needs to be exercised when interpreting research findings due to important methodological issues.
The Health Technology Assessment (HTA) researchers at the Institute of Health Economics, in collaboration with researchers from two HTA agencies in Australia and Spain, developed, piloted, and validated a 20-criteria quality appraisal checklist specific for case series studies (before-after single arm studies with no control group) (1,2). Since its publication in 2012, the use of the checklist has spread globally through the HTA community and to researchers in other areas. This presentation will briefly introduce the tool, summarize user experiences, outline potential challenges, and provide practical solutions for using or adapting the checklist to various HTA topics.
Feedback from fifteen researchers was collected informally by email and/or formally by questionnaire. The questions included focused on the relevance, clarity, and usefulness of the checklist and its instructions, as well as potential revisions and/or addition of other criteria.
While some of the checklist's criteria apply to all studies of a particular type, others are specific to the research question and/or the technology under investigation; discussion on the modification and/or adaptation of the checklist and its instructions is therefore required before commencing appraisal. Some criteria are difficult to score owing to study reporting limitations. Quality assessment can be challenging when multiple types of studies are included; however, currently there is no single universally validated tool available for diverse study designs. There are frequent demands for a cut-off point in order to separate high- from low-quality studies. However, no scale or numeric scoring was developed for the checklist, due to the well-recognized risks associated with such a scoring system.
The increased use of the checklist and general positive feedback indicates the need for such a tool. User feedback helped improve our understanding of the checklist's applicability with various topics, as well as the potential refinements needed to increase its utility and robustness.