A Multi-dimensional Framework of Valued Output for Primary Care in England.

Improving efficiency and productivity are key aspects to ensure that general practices in England can meet the needs of a growing population with increasingly demanding and costly healthcare needs. However, current evidence on the efficiency and productivity of general practices is weak, partly due to suboptimal approaches to measure their 'valued' output. To overcome this limitation, this paper presents a multi-dimensional framework and indicators of valued output from the healthcare decision-maker's perspective. We identified existing primary care performance frameworks through a targeted literature review. We reviewed the frameworks and selected the dimensions relating to the impact on patients' health outcomes, corresponding with the definition of 'valued' output from the healthcare decision-maker perspective. For each dimension, we reviewed the National Institute for Health and Care Excellence (NICE) evidence base and guidance on best practice to develop indicators of valued output. Clinical experts and representatives of the main primary care stakeholders reviewed and validated the framework's comprehensiveness and development process. Based on a review of three existing frameworks, we synthesised a multi-dimensional output framework comprising 13 dimensions for significant primary care-related conditions and services and 51 indicators of valued output. Each indicator of valued output measures a healthcare episode and the resulting impact on patient's health. The multi-dimensional framework and indicators provide a theoretical tool to improve the measurement of primary care output in economic efficiency and productivity studies. Future research should explore the measurability of the indicators through available datasets and the implementation of the framework through analytical approaches for efficiency measurement.

Cardiac SARS-CoV-2 Infection, Involvement of Cytokines in Postmortem Immunohistochemical Study.

In the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, significant attention was given to pulmonary manifestations. However, cardiac involvement is increasingly recognized as a critical factor influencing the prognosis, leading to myocardial damage, heart failure, acute coronary syndromes, potentially lethal arrhythmic events, and sudden cardiac death. Despite these findings, there is a lack of studies detailing the necroscopic, macroscopic, and microscopic cardiac changes associated with SARS-CoV-2. This study aimed to investigate the presence of SARS-CoV-2 viral proteins in cardiac tissue using immunohistochemical techniques to assess viral tropism. The analysis of cardiac tissue samples from deceased subjects, in different stages of conservation, confirmed to be positive for SARS-CoV-2 via reverse transcriptase-polymerase chain reaction (RT-PCR), showed immunopositivity for the SARS-CoV-2-NP viral antigen in 33% of cases. Notably, the presence of leukocyte infiltrates sufficient for diagnosing lymphocytic myocarditis was not observed. The central proinflammatory cytokines involved in the pathogenetic mechanism of coronavirus disease 19 (COVID-19) were researched using the immunohistochemical method. A significant increase in cytokine expression was detected, indicating myocardial involvement and dysfunction during SARS-CoV-2 infection. These findings suggest that the immunohistochemical detection of SARS-CoV-2 viral antigens and inflammatory cytokine expression in cardiac tissue could be crucial for a proper forensic assessment of the cause of death, even in sudden cardiac death.

Impact of including productivity costs in economic analyses of vaccines for C. difficile infections and infant respiratory syncytial virus, in a UK setting.

OBJECTIVES: It has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated. METHODS: For two vaccines currently under development, one against Cloistridioides difficile (C. difficile) infection and one against respiratory syncytial disease (RSV), we estimated their incremental costs with and without productivity value included and compared the results. RESULTS: In this analysis, reflecting a UK context, a C. difficile vaccination programme would prevent £12.3 in productivity costs for every person vaccinated. An RSV vaccination programme would prevent £49 in productivity costs for every vaccinated person. CONCLUSIONS: Considering productivity costs in future cost-effectiveness analyses of vaccines for C. difficile and RSV will contribute to better-informed reimbursement decisions from a societal perspective.

Application of Aquaporins as Markers in Forensic Pathology: A Systematic Review of the Literature.

The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the manner of death and for the individuation of forensic markers for the timing of lesions and vitality of injury. In the literature, various tissues have been studied; the most investigated are the lungs, brain, kidneys, skin, and blood vessels. A systematic literature review on PubMed following PRISMA 2020 guidelines enabled the identification of 96 articles. In all, 34 of these were enrolled to identify Aquaporin-like (AQP-like) forensic markers. The analysis of the literature demonstrated that the most significant markers among the AQPs are as follows: for the brain, AQP4, which is very important in brain trauma and hypoxic damage; AQP3 in the skin lesions caused by various mechanisms; and AQP5 in the diagnosis of drowning. Other applications are in organ damage due to drug abuse and thrombus dating. The focus of this review is to collect all the data present in the literature about the forensic application of AQPs as forensic markers in the most important fields of application. In the current use, the individuation, validation, and application of markers in forensic investigation are very useful in real forensic applications in cases evaluated in court.

Macroscopic and Microscopic Cerebral Findings in Drug and Alcohol Abusers: The Point of View of the Forensic Pathologist.

Drug abuse still represents a significant challenge for forensic pathologists; it must always be considered during the autopsy examination when the brain morphological alterations observed are not characteristic of any known disease of the central nervous system (CNS). Nonetheless, no specific brain lesions had been found to characterize the precise drug that caused the poisoning. In fact, a broad spectrum of changes affecting the CNS are seen in drug abusers. Thus, forensic pathology plays a key role in identifying the encephalic morphological alterations underlying the death. The aim of this review is to present an updated overview of the literature regarding the correlation between the main substances of abuse and the morphological alterations of the CNS to help the forensic pathologist to discriminate drug-induced alterations of the brain. The authors used the PRISMA criteriology to perform the bibliographic search for the present review. Among the articles identified according to the selected search criteria, 116 articles were chosen which allow us to define a picture of the main macroscopic and microscopic alterations of the brain in drug abuse.

Effect of Repeated Administration of ɣ-Valerolactone (GVL) and GHB in the Mouse: Neuroadaptive Changes of the GHB and GABAergic System.

BACKGROUND: Gamma-hydroxybutyric acid (GHB) at low dosages has anxiolytic effects and promotes REM sleep and low-wave deep sleep. In the U.S., the legal form of GHB is prescribed to adults suffering from narcolepsy-associated cataplexy; the sodium salt of GHB is reserved for alcohol-addiction treatment. GHB is also a molecule of abuse and recreational use, it is a controlled substance in several countries, so gamma-valerolactone (GVL) has frequently been used as a legal substitute for it. GHB's abuse profile is most likely attributable to its anxiolytic, hypnotic, and euphoric properties, as well as its widespread availability and inexpensive/low cost on the illicit market. METHODS: Our study is focused on evaluating the potential effects on the mouse brain after repeated/prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) through behavioral study and immunohistochemical analysis using the markers tetraspanin 17 (TSPAN17), aldehyde dehydrogenase 5 (ALDH5A1), Gamma-aminobutyric acid type A receptor (GABA-A), and Gamma-aminobutyric acid type B receptor (GABA-B). RESULTS: Our findings revealed that prolonged administration of GHB and GVL at a pharmacologically active dose (100 mg/kg) can have effects on a component of the mouse brain, the intensity of which can be assessed using immunohistochemistry. The findings revealed that long-term GHB administration causes a significant plastic alteration of the GHB signaling system, with downregulation of the putative binding site (TSPAN17) and overexpression of ALDH5A1, especially in hippocampal neurons. Our findings further revealed that GABA-A and GABA-B receptors are downregulated in these brain locations, resulting in a greater decrease in GABA-B expression. CONCLUSIONS: The goal of this study, from the point of view of forensic pathology, is to provide a new methodological strategy for better understanding the properties of this controversial substance, which could help us better grasp the unknown mechanism underlying its abuse profile.

Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study.

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.

Recognizing the Broader Value of Meningococcal Vaccination: A Matter of Evidence, Ability, or Willingness?

OBJECTIVES: It is widely argued that the value of meningococcal vaccination extends beyond the narrow value elements traditionally considered in health technology assessment. Nevertheless, measuring broader value presents challenges, whereas assessment methods and outcomes vary widely. This article investigates the extent to which the broader value of meningococcal vaccination is recognized, considering the available evidence and decision maker's methodological ability and willingness. METHODS: A targeted literature review informed the classification of broader value elements according to their relevance to meningococcal vaccination and the quality of existing evidence. Focusing on relevant value elements with good evidentiary standards, decision makers' perspectives and methodological ability to consider them were assessed through case studies of health technology assessment of meningococcal B vaccination in England and The Netherlands. RESULTS: Value elements of high relevance to meningococcal vaccination with good quality evidence include caregivers' health gains, patients' lifetime productivity gains, and disease severity. The willingness and methodological ability to incorporate them into value assessments have been mixed. This is attributable to the scope of the value assessment perspective and the use of evaluation methods that do not fully capture broader value. For other broader value elements, evidence gaps are another potential barrier to value demonstration and recognition. CONCLUSIONS: The current evidence base confirms that the value of meningococcal vaccination spans beyond healthcare sector effects to health-related externalities, allocative value, and societal economic benefits. To ensure that the most efficient resource allocation outcomes are achieved, countries should consider how to improve their perspective and methodological ability to assess broader value elements accurately.

Vaccine-Preventable Hospitalisations from Seasonal Respiratory Diseases: What Is Their True Value?

Hospitals in England experience extremely high levels of bed occupancy in the winter. In these circumstances, vaccine-preventable hospitalisations due to seasonal respiratory infections have a high cost because of the missed opportunity to treat other patients on the waiting list. This paper estimates the number of hospitalisations that current vaccines against influenza, pneumococcal disease (PD), COVID-19, and a hypothetical Respiratory Syncytial Virus (RSV) vaccine, could prevent in the winter among older adults in England. Their costs were quantified using a conventional reference costing method and a novel opportunity costing approach considering the net monetary benefit (NMB) obtained from alternative uses of the hospital beds freed-up by vaccines. The influenza, PD and RSV vaccines could collectively prevent 72,813 bed days and save over £45 million in hospitalisation costs. The COVID-19 vaccine could prevent over 2 million bed days and save £1.3 billion. However, the value of hospital beds freed up by vaccination is likely to be 1.1-2 times larger (£48-93 million for flu, PD and RSV; £1.4-2.8 billion for COVID-19) when quantified in opportunity cost terms. Considering opportunity costs is key to ensuring maximum value is obtained from preventative budgets, as reference costing may significantly underestimate the true value of vaccines.

Application of Forensic DNA Phenotyping for Prediction of Eye, Hair and Skin Colour in Highly Decomposed Bodies.

In the last few years, predicting externally visible characteristics (EVCs) by adopting informative DNA molecular markers has become a method in forensic genetics that has increased its value, giving rise to an interesting field called "Forensic DNA Phenotyping" (FDP). The most meaningful forensic applications of EVCs prediction are those in which, having only a DNA sample isolated from highly decomposed remains, it is essential to reconstruct the physical appearance of a person. Through this approach, we set out to evaluate 20 skeletal remains of Italian provenance in order to associate them with as many cases of missing persons as possible. To achieve the intended goal, in this work we applied the HIrisPlex-S multiplex system through the conventional short tandem repeats (STR) method to confirm the expected identity of subjects by evaluating phenotypic features. To investigate the reliability and accuracy of the DNA-based EVCs prediction, pictures of the cases were compared as they were available to researchers. Results showed an overall prediction accuracy greater than 90% for all three phenotypic features-iris, hair, and skin colour-at a probability threshold of 0.7. The experimental analysis showed inconclusive results in only two cases; this is probably due to the characteristics of subjects who had an intermediate eye and hair colour, for which the DNA-based system needs to improve the prediction accuracy.

Pharmaco-Toxicological Effects of Atypical Synthetic Cathinone Mephtetramine (MTTA) in Mice: Possible Reasons for Its Brief Appearance over NPSs Scene.

Over the last year, NPSs have been steadily on the rise in the illicit drug market. Among these, synthetic cathinones seem to become increasingly popular among young adults, mainly because of their ability to replicate the effects of traditional psychostimulant drugs, such as cocaine, MDMA and amphetamines. However, scarce data are available about the in vivo pharmaco-toxicology of these new substances. To this end, this study focused on evaluation of effects induced by repeated administration of mephtetramine (MTTA 0.1-30 mg/kg i.p.) in mice. This atypical cathinone highlighted a sensorial (inhibition of visual and acoustic reflexes) and transient physiological parameter (decrease in breath rate and temperature) change in mice. Regarding motor activity, both a dose-dependent increase (accelerod test) and biphasic effect (drag and mobility time test) have been shown. In addition, blood and urine samples have been analysed to enrich the experimental featuring of the present study with reference to evaluation of potential toxicity related to consumption of MTTA. The latter analysis has particularly revealed important changes in blood cells count and blood and urine physicochemical profile after repeated treatment with this atypical cathinone. Moreover, MTTA induced histological changes in heart, kidney and liver samples, emphasizing its potential toxicity.

Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic.

BACKGROUND: Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented. AIM: To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients. METHODS: A systematic literature search on PubMed was carried out until June 21, 2022. RESULTS: A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common; liver enzyme elevations tend to be seen in those in critical conditions. Despite the poor expression of viral receptors in the liver, it seems that the virus is able to infect this organ and therefore cause liver damage. Unfortunately, to date, the search for the virus inside the liver is not frequent (16% of the cases) and only a small number show the presence of the virus. In most of the autopsy cases, macroscopic assessment is lacking, while microscopic evaluation of livers has revealed the frequent presence of congestion (42.7%) and steatosis (41.6%). Less frequent is the finding of hepatic inflammation or necrosis (19%) and portal inflammation (18%). The presence of microthrombi, frequently found in the lungs, is infrequent in the liver, with only 12% of cases presenting thrombotic formations within the vascular tree. CONCLUSION: To date, the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus, rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.

The Value of Vaccines in Maintaining Health System Capacity in England.

OBJECTIVES: In situations of excess demand for healthcare, treating one patient means losing the opportunity to treat another. Therefore, each decision bears an opportunity cost. Nevertheless, when assessing the value of health technologies, these opportunity costs are not always fully considered. We present a pragmatic approach for conceptualizing vaccines' health system capacity value when considering opportunity costs. METHODS: Our approach proxies opportunity costs through the net monetary benefit forgone as scarce healthcare resources are used to treat a vaccine-preventable disease instead of a patient from the waiting list. We apply this approach to cost the resource "hospital beds" for 3 different scenarios of excess demand. Empirically, we estimate the opportunity costs saved for 4 selected vaccination programs from the national schedule in England during a hypothetical scenario of long-lasting excess demand induced by the pandemic. RESULTS: The opportunity cost avoided through vaccination rises with excess demand for treatment. When treating an acute vaccine-preventable outcome is a suboptimal choice compared with treating elective patients, preventing a vaccine-preventable disease from blocking a hospital bed generates opportunity cost savings of approximately twice the direct costs saved by avoiding vaccine-preventable hospitalizations. CONCLUSIONS: Policy makers should be aware that, in addition to preventing the outcome of interest, vaccines and other preventative health technologies deliver value in maintaining regular healthcare services and clearing the pent-up demand from the pandemic. Therefore, health system capacity value should be a key-value element in health technology assessment. Existing and potential future vaccination programs deliver more value than hitherto quantified.

SARS-CoV-2 Infection Prompts IL-1ß-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue.

Two years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune-inflammatory pathways that prompt the manifestation of the disease to identify a novel potential target for pharmacological intervention. In this context, the characterization of the main players in the SARS-CoV-2-induced cytokine storm is mandatory. To date, the most characterized have been IL-6 and the class I and II interferons, while less is known about the proinflammatory cytokine IL-1ß and class III interferons. Here, we report a preliminary study aimed at the characterization of the lung inflammatory context in COVID-19 patients, with a special focus on IFN-λ and IL-1ß. By investigating IFN and inflammatory cytokine patterns by IHC in 10 deceased patients due to COVID-19 infection, compared to 10 control subjects, we reveal that while IFN-ß production was increased in COVID-19 patients, IFN-λ was almost abolished. At the same time, the levels of IL-1ß were dramatically improved, while IL-6 lung levels seem to be unaffected by the infection. Our findings highlight a central role of IL-1ß in prompting lung inflammation after SARS-CoV-2 infection. Together, we show that IFN-λ is negatively affected by viral infection, supporting the idea that IFN-λ administration together with the pharmaceutical blockage of IL-1ß represents a promising approach to revert the COVID-19-induced cytokine storm.

Forensic Diagnosis of Freshwater or Saltwater Drowning Using the Marker Aquaporin 5: An Immunohistochemical Study.

Background and Objectives: Aquaporins are a family of water channel proteins. In this study, the renal and intrapulmonary expression of aquaporin-5 (AQP5) was examined in forensic autopsy cases to evaluate it as a drowning marker and to differentiate between freshwater drowning and saltwater drowning. Materials and Methods: Cases were classified into three groups: freshwater drowning (FWD), saltwater drowning (SWD), and controls (CTR). Samples were obtained from forensic autopsies at less than 72 h postmortem (15 FWD cases, 15 SWD cases, and 17 other cases) and were subjected to histological and immunohistochemical investigations. Results: In FWD group, intrapulmonary AQP5 expression was significantly suppressed compared with SWD and CTR; there was no significant difference in AQP5 expression among the other two groups. The same differences in expression were also observed in the kidney. Conclusions: These observations suggest that AQP5 expression in alveolar cells was suppressed by hypotonic water to prevent hemodilution. Moreover, it is possible to hypothesize that in the kidney, with the appearance of hypo-osmotic plasma, AQP5 is hypo-expressed, as a vital reaction, to regulate the renal reabsorption of water. In conclusion, the analysis of renal and intrapulmonary AQP5 expression would be forensically useful for differentiation between FWD and SWD, or between FWD and death due to other causes.

Tooth Cementum Thickness as a Method of Age Estimation in the Forensic Context.

Estimating age at death is a key element in the process of human identification of skeletal remains. The interest in dental cementum stems from its increase in thickness throughout life and, at the same time, from the fact it should not be affected by remodeling processes. Since the age assessment is particularly difficult in adults when using traditional anthropological methods on the skeleton, we tested a dental method based on maximum cementum thickness and developed new regression equations. We microscopically analyzed the histological sections of dental roots from a sample of 108 permanent teeth with known age and sex. Age at the time of dental extraction was in the range of 18-84 years. Our findings show that there were no differences in thickness between sexes, dental arch, and mono- and pluriradicular teeth. Separate regression equations were developed for individuals in the whole age range and individuals under 45 years. The equations were then tested on a hold-out sample from the same Mediterranean population demonstrating higher reliability for the equation developed for those under 45. Conversely, due to the increased error in age estimation in individuals over 45, this method should be used with caution in the forensic context when skeletal remains presumably belong to elderly individuals.

Age estimation using tooth cementum annulations: bias and sources of inaccuracy.

BACKGROUND: Counting the tooth cementum annulations (TCA) is a method for estimating the age at death of adults by sections of their tooth root. The objective of this study was to assess the precision of counting the cementum incremental lines and the congruence between known age and age estimates. Possible factors affecting the accuracy of the estimate were also analyzed. METHODS: A sample of 67 permanent teeth extracted from individuals with known age (18-84 years) and sex was analyzed to calculate the dental age. RESULTS: Results demonstrate an excellent inter- and intra-observer reliability of annuli counting, with dissimilarities within the limits of agreement. A moderate positive correlation was found between chronological age and TCA. Our results showed that age congruence rates differed across age groups (85% congruence in individuals ≤30 years; 75% in individuals aged 31-60 years; 60% in the over 60s). Considering the bias, this method showed a clear tendency to underestimate age in specimens from old people. After age 43, the TCA estimate is highly inaccurate exceeding the underestimation of 10 years, on average, in comparison to the chronological age. Both chronological age and dental arch seem to influence the accuracy of estimates, unlike sex and the tooth root number. CONCLUSIONS: TCA analysis is characterized by high precision and low accuracy, decreasing with age. Therefore, its applicability is limited in elderly subjects. The choice of methods for age estimation in adult skeletal remains should take into account the particular age range of individuals. We recommend using different age estimation methods to verify the reliability of the performed assessments.

Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1ß, IL-6, IL-15 and TNF-α.

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1ß, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1ß in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Towards a Broader Assessment of Value in Vaccines: The BRAVE Way Forward.

BACKGROUND: The COVID-19 pandemic shows that the impact of effective vaccines can extend well beyond vaccinated individuals and healthcare systems. Yet, these broader value elements are not typically considered in Health Technology Assessment (HTA) which may underestimate vaccines' broader value. OBJECTIVES: This study aimed to (1) describe the gap between broader value elements identified in value frameworks for vaccines and those recognised in HTA of vaccines in nine developed markets, and (2) develop expert-informed, consensus-based recommendations on how hurdles for broader value recognition could be overcome. METHODS: We used a four-step modified Delphi method consisting of literature research (phase I, pearl-growing approach using PubMed Web of Science and Google covering the years 2000-2019), two consecutive phases of expert elicitation (phase II and III, including two email surveys and one virtual round table with 10 experts from 9 countries) and synthesis of recommendations (phase IV). RESULTS: Results show that about half of the broader value elements relevant to vaccines are not (consistently) considered in HTA processes of multiple higher-income countries. Experts identified five priority areas for broader value recognition, including considering (1) more comprehensive cost offsets within the health care system, (2) carer quality of life, (3) transmission value, (4) prevention of antimicrobial resistance and (5) macroeconomic effects. CONCLUSION: To achieve a broader recognition of the value of vaccines, a three-pronged approach was recommended, focusing on (1) Evidence: proactively steering generation of high-quality evidence to quantify the broader value of vaccines to society; (2) Ability: leveraging and further developing existing methodological and analytic expertise to appropriately recognise the broad value of vaccines within HTA processes; (3) Willingness: Stimulating stakeholder engagement to change the status quo and move towards more transparent and comprehensive value assessment processes for vaccines globally.

Approaches to Measure Efficiency in Primary Care: A Systematic Literature Review.

BACKGROUND: Primary care in England is facing increasing pressure due to the increasing number and complexity of consultations and the declining number of doctors per head of population. The improvement of primary care efficiency and productivity should be a priority, to ensure that future investments in the medical workforce can cope with the increasingly large and complex demand for care. OBJECTIVES: This paper presents a systematic literature review of studies that define or measure efficiency in primary care in high-income settings. The review of the existing definitions of primary care efficiency and their limitations will inform future research on the measurement of efficiency in primary care in England and its determinants. METHODS: Literature searches were performed on Embase, Medline, and EconLit in January 2020. The records that passed the screening were reviewed in full text, and data on the study settings, the efficiency definition, and the efficiency analysis were extracted. RESULTS: Of the 2590 non-duplicate records retrieved from the searches, 38 papers were included in the analysis. The volume of the literature on primary care efficiency has evolved significantly from the 1980s, with the majority of the published studies focussing on European health systems. The setting most often analysed was primary care centres. Output was usually expressed using measures of primary care utilisation, with or without quality adjustments. Reference to the health outcomes achieved was, however, limited. Inputs were more commonly expressed in labour terms, while the exogenous variables related either to the characteristics of the patient population or the organisation of primary care. While all studies included an analysis of technical efficiency, consideration of allocative or cost efficiency or the determinants of productivity (e.g. technological change, skill mix) was rare. CONCLUSIONS: The main limitations that future research on primary care efficiency should address relate to the definition of output. Current approaches to measure the impact on health and the multiple dimensions of output are not sufficient to represent the valued output of primary care. In light of the recent changes in the model of primary care delivery in England, future research should also investigate the impact of technological change on productivity and the scope for substitution across staff roles.