The global health and economic value of COVID-19 vaccination.

INTRODUCTION: The COVID-19 pandemic triggered one of the largest global health and economic crises in recent history. COVID-19 vaccination (CV) has been the central tool for global health and macroeconomic recovery, yet estimates of CV's global health and macroeconomic value remain scarce. METHODS: We used regression analyses to measure the impact of CV on gross domestic product (GDP), infections and deaths. We combined regression estimates of vaccine-averted infections and deaths with estimates of quality-adjusted life years (QALY) losses, and direct and indirect costs, to estimate three broad value components: (i) QALY gains, (ii) direct and indirect costs averted and (iii) GDP impacts. The global value is the sum of components over 148 countries between January 2020 and December 2021 for CV generally and for Pfizer-BioNTech specifically. RESULTS: CV's global value was US$5.2 (95% CI US$4.1 to US$6.2) trillion, with Pfizer-BioNTech's vaccines contributing over US$1.9 (95% CI US$1.5 to US$2.3) trillion. Varying key parameters results in values 10%-20% higher or lower than the base-case value. The largest value component was GDP impacts, followed by QALY gains, then direct and indirect costs averted. CV provided US$740 of value per dose, while Pfizer-BioNTech specifically provided >US$1600 per dose. We estimated conservative benefit-cost ratios of 13.9 and 30.8 for CV and Pfizer-BioNTech, respectively. CONCLUSIONS: We provide the first estimates of the broad value of CV incorporating GDP, QALY and direct and indirect cost impacts. Through December 2021, CV produced significant health and economic value, represented strong value for money and produced significant macroeconomic benefits that should be considered in vaccine evaluation.

Modeling the potential public health impact of different vaccination strategies with an adapted vaccine in South Africa.

BACKGROUND: COVID-19 vaccines adapted to newly emerging circulating variants are necessary to better protect the population due to the evolving nature of the SARS-CoV-2 virus. RESEARCH DESIGN AND METHODS: The South African population was stratified by age and risk (defined by comorbidities such as diabetes, obesity, smoking, cancer, and asthma), and HIV status. The outcomes of different vaccination strategies based on age, risk, and HIV status were estimated using a Markov-decision tree model based on age-specific inputs derived from the literature and South African surveillance data. RESULTS: Vaccinating older adults and those with comorbidities was estimated to avert 111,179 infections 18,281 hospitalizations, and 3,868 deaths, resulting in savings of ZAR 1,260 million (USD 67 million) and ZAR 3,205 million (USD 170 million) in direct and indirect costs, respectively. Similar results were obtained when considering strategies targeting older adults and the HIV population. Expanding vaccination to 75% of the standard-risk population prevented more infections (401%), hospitalizations (167%), and deaths (67%) and increased the direct (232%) and indirect (455%) cost savings compared to the base case. CONCLUSIONS: Implementing widespread vaccination strategies that utilize a vaccine adapted to the prevailing circulating variant in South Africa would result in significant public health and economic gains.

Effect of repetitive up-and-down movements on torque/force generation, surface defects and shaping ability of nickel-titanium rotary instruments: an ex vivo study.

BACKGROUND: The screw-in effect is a tendency of a nickel-titanium (NiTi) rotary endodontic file to be pulled into the canal, which can result in a sudden increase in stress leading to instrument fracture, and over-instrumentation beyond the apex. To reduce screw-in force, repeated up-and-down movements are recommended to distribute flexural stress during instrumentation, especially in curved and constricted canals. However, there is no consensus on the optimal number of repetitions. Therefore, this study aimed to examine how repeated up-and-down movements at the working length affect torque/force generation, surface defects, and canal shaping ability of JIZAI and TruNatomy instruments. METHODS: An original automated root canal instrumentation device was used to prepare canals and to record torque/force changes. The mesial roots of human mandibular molars with approximately 30˚ of canal curvature were selected through geometric matching using micro-computed tomography. The samples were divided into three groups according to the number of up-and-down movements at the working length (1, 3, and 6 times; n = 24 each) and subdivided according to the instruments: JIZAI (#13/0.04 taper, #25/0.04 taper, and #35/0.04 taper) or TruNatomy (#17/0.02 taper, #26/0.04 taper, and #36/0.03 tape) (n = 12 each). The design, surface defects, phase transformation temperatures, nickel-titanium ratios, torque, force, shaping ability, and surface deformation were evaluated. Data were analyzed with the Kruskal-Wallis and Dunn's tests (α = 0.05). RESULTS: The instruments had different designs and phase transformation temperatures. The 3 and 6 up-and-down movements resulted in a smaller upward force compared to 1 movement (p < 0.05). TruNatomy generated significantly less maximum torque, force, and surface wear than JIZAI (p < 0.05). However, TruNatomy exhibited a larger canal deviation (p < 0.05). No statistical differences in shaping ability were detected between different up-and-down movements. CONCLUSIONS: Under laboratory conditions with JIZAI and TruNatomy, a single up-and-down movement at the working length increased the screw-in force of subsequent instruments in severely curved canals in the single-length instrumentation technique. A single up-and-down movement generated more surface defects on the file when using JIZAI. TruNatomy resulted in less stress generation during instrumentation, while JIZAI better maintained the curvature of root canals.

Severe COVID-19 Outcomes in Five Latin American Countries in the Postvaccination Era.

We conducted a multicountry retrospective study using data from COVID-19 national surveillance databases to analyze clinical profiles, hospitalization rates, intensive care unit (ICU) admissions, utilization of ventilatory support, and mortality rates in five Latin American countries in the context of COVID-19 vaccination implementation. We analyzed the sociodemographic characteristics, comorbidities, clinical outcomes, and vaccination status of laboratory-confirmed COVID-19 cases from January 2021 to December 2022. We calculated the yearly and quarterly hospitalization rates per 1000 confirmed COVID-19 cases and ICU admissions, use of mechanical ventilators, and mortality rates per 1000 hospitalized cases, with their corresponding 95% confidence interval (CI) of 38,852,831 confirmed COVID-19 cases. Rates of hospitalization, ICU admission, ventilatory support, and death were higher among males than among females (38.2 vs. 32.4, 148.4 vs. 117.7, 282.9 vs. 236.2, and 346.9 vs. 320.1 per 1000, respectively); higher in 2021 than in 2022 (50.7 vs. 19.9, 207.8 vs. 58.2, 441.5 vs. 114.9, and 352.5 vs. 285.2 per 1000, respectively); and in the >50 age group (range: 5.7-18.6, 20.1-71.5, 12.2-67.9, and 353.1-577.4, per 1000) than the <50 age group (range: 2.2-9.3, 5.4-33.2, 41.4-135.8, and 22-243.5 per 1000). Hypertension and diabetes mellitus were the most common comorbidities in Mexico and Colombia. Prevention and treatment strategies for these case profiles could bring benefits from a public health perspective.

Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5-11 years of age in Brazil: A prospective test-negative design study.

OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).

Retrospective Analysis of Clinical Characteristics and Disease Outcomes in Children and Adolescents Hospitalized Due to COVID-19 Infection in Tunisia.

Due to low susceptibility of coronavirus disease of 2019 (COVID-19) in children, limited studies are available regarding COVID-19 in the pediatric population in Tunisia. The current study evaluated the incidence, clinical characteristics, and outcomes of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection among children hospitalized at Béchir Hamza Children's Hospital. A retrospective cohort analysis was conducted using the hospital database between March 2020 and February 2022 with children aged ≤15 years with SARS-CoV-2 infection (confirmed by RT-PCR). A total of 327 COVID-19 hospitalized patients with a mean age of 3.3 years were included; the majority were male. Neurological disease (20%) was the most common comorbidity, while fever (95.3%) followed by cough (43.7%) and dyspnea (39.6%) were the most frequent symptoms reported. Severe disease with oxygen requirement occurred in 30% of the patients; 13% were admitted in the Intensive Care Unit. The overall incidence rate of COVID-19 hospitalization (in Tunis governorates) was 77.02 per 100,000 while the inpatient case fatality rate was 5% in the study population. The most prevalent circulating variant during our study period was Delta (48.8%), followed by Omicron (26%). More than 45% of the study population were <6 months and one-fourth (n = 25, 26.5%) had at least one comorbidity. Thus, the study findings highlight the high disease burden of COVID-19 in infants.

Pediatric COVID-19 in Argentina: a comprehensive analysis of disease and economic burden through official data and a systematic literature review.

Background: Limited data are available on the clinical impact and economic burden of COVID-19 in the pediatric population in Argentina. We aimed to estimate the disease and economic burden of COVID-19 on children and adolescents. Methods: We analyzed official national databases and conducted a supplemental systematic review of the published literature with meta-analysis in children aged 0-18. The period of interest was from March 2020 to August 2021, before the introduction of vaccination in this age group as a national strategic plan. In addition, we used a cost of illness analysis to estimate the direct medical costs associated with COVID-19. All costs are reported in US dollars 2023. Results: A total of 450,503 confirmed COVID-19 cases and 180 multisystem inflammatory syndrome (MIS-C) were reported in Argentina in the study period. Fourteen observational clinical studies were identified. The meta-analyses of severity level from hospital patients showed that according to different studies 15%-28% of cases were asymptomatic, 68%-88% were mild or moderate, and 3%-10% were severe or critical. About 28% of children had an underlying disease. In addition, the estimated economic burden associated with COVID-19 was 80 million dollars and 4 million dollars corresponded to MISC. Conclusion: Significant impact of COVID-19 on the healthcare system and substantial economic implications for the pediatric population in Argentina were identified. The findings should help policymakers to make informed decisions and allocate resources effectively.

Phase transformation behavior and mechanical properties of HyFlex EDM nickel-titanium endodontic rotary instrument: Evaluation at body temperature.

Background/purpose: Temperature-dependent phase compositional changes influence the mechanical properties of heat-treated nickel-titanium (NiTi) rotary instruments. This study evaluated the phase composition, bending properties, and cyclic fatigue resistance of HyFlex EDM NiTi rotary instruments against differently heat-treated and non-heat-treated NiTi instruments at body temperature (BT). Materials and methods: HyFlex EDM OneFile (EDM) instruments, heat-treated HyFlex CM (CM) and Twisted File (TF) instruments, and non-heat-treated K3 instruments (size #25/.08) were subjected to differential scanning calorimetry, and the martensitic, R-phase, and reverse transformation starting and finishing temperatures were determined. A cantilever bending test and a cyclic fatigue test were conducted at BT (37 °C ± 1.0 °C), and the bending load and number of cycles to failure (NCF) were recorded. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests (α = 0.05). Results: TF and K3 had reverse transformation finishing temperatures lower than BT, while those for EDM and CM were higher than BT. The bending loads at a 0.5 mm deflection were in the order of EDM < TF < CM < K3 (P < 0.05), and those at a 2.0 mm deflection were EDM < CM and TF < K3 (P < 0.05). EDM had the highest NCF among the four instruments (P < 0.05). Conclusion: The EDM instrument had a reverse transformation finishing temperature higher than BT indicating its martensite/R-phase composition at BT. The EDM instrument had superior flexibility and greater resistance to cyclic fatigue than the CM, TF, and K3 instruments at BT.

First characterization of major histocompatibility complex class II DRB3 diversity in cattle breeds raised in Egypt.

Genes encoding bovine leukocyte antigen (BoLA) enable the immune system to identify pathogens. Therefore, these genes have been used as genetic markers for infectious and autoimmune diseases as well as for immunological traits in cattle. Although BoLA polymorphisms have been reported in various cattle breeds worldwide, they have not been studied in cattle populations in Egypt. In this study, we characterized BoLA-DRB3 in two local Egyptian populations and one foreign population using polymerase chain reaction-sequence-based typing (PCR-SBT) method. Fifty-four previously reported BoLA-DRB3 alleles and eight new alleles (BoLA-DRB3*005:08, *015:07, *016:03, *017:04, *020:02:02, *021:03, *164:01, and *165:01) were identified. Alignment analysis of the eight new alleles revealed 90.7-98.9 %, and 83.1-97.8 % nucleotide and amino acid identities, respectively, with the BoLA-DRB3 cDNA clone NR-1. Interestingly, BoLA-DRB3 in Egyptian cattle showed a high degree of allelic diversity in native (na = 28, hE > 0.95), mixed (na = 61, hE > 0.96), and Holstein (na = 18, hE > 0.88) populations. BoLA-DRB3*002:01 (14.3 %), BoLA-DRB3*001:01 (8.5 %), and BoLA-DRB3*015:01 (20.2 %) were the most frequent alleles in native, mixed, and Holstein populations, respectively, indicating that the genetic profiles differed in each population. Based on the allele frequencies of BoLA-DRB3, genetic variation among Egyptian, Asian, African, and American breeds was examined using Nei's distances and principal component analysis. The results suggested that native and mixed cattle populations were most closely associated with African breeds in terms of their gene pool, whereas Holstein cattle were more distinct from the other breeds and were closely related to Holstein cattle populations from other countries.

Effect of preset torque setting on torque/force generation, shaping ability and surface changes of nickel titanium rotary instrument in different root canal curvature locations: An ex vivo study.

The aim of this study was to evaluate how preset torque settings influence the torque, vertical force, and root canal-centering ability of ProGlider and ProTaper NEXT nickel-titanium rotary instruments in canals with different curvature locations. Based on micro-computed tomography, mesial roots of human mandibular molars (25°-40° curvature) were allocated to the apical curvature (apical 1-5 mm) or the middle curvature (apical 5-9 mm) groups, and mandibular incisors (curvature <5°) to the straight canal group. Each group was subjected to automated instrumentation and torque/force measurement with the preset torque of 1, 2.5, or 5 N•cm. Canal-centering ratios were determined with micro-computed tomography. Instrument fracture occurred only in the 2.5 and 5 N•cm groups in curved canals. The preset torque setting and curvature location did not influence canal shaping ability.

Duration of SARS-CoV-2 shedding: A systematic review.

Background: Positive viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cultures indicate shedding of infectious virus and corresponding transmission risk of coronavirus disease 2019 (COVID-19). The research question of this systematic review was: Is there a discernible pattern in the timing of SARS-CoV-2 virus isolation, and what is the proportion of positive and negative results for isolation of SARS-CoV-2 virus with viral culture relative to the onset of clinical symptoms or the day of diagnosis, as indicated by longitudinal studies? Methods: We systematically searched PubMed and Embase from inception to 16 February 2023 for English-language studies with serial viral culture testing within symptomatic or asymptomatic SARS-CoV-2 infected persons during the post-vaccination period. Outcomes of interest were the daily culture status per study and the overall daily culture positivity rate of SARS-CoV-2. We critically appraised the selected studies using the Newcastle-Ottawa quality assessment scale. Results: We included 14 viral shedding studies in this systematic review. Positive viral SARS-CoV-2 cultures were detected in samples ranging from 4 days before to 18 days after symptom onset. The daily culture SARS-CoV-2 positivity rate since symptom onset or diagnosis showed a steep decline between day 5 and 9, starting with a peak ranging from 44% to 50% on days -1 to 5, decreasing to 28% on day 7 and 11% on day 9, and finally ranging between 0% and 8% on days 10-17. Conclusions: Viral shedding peaked within 5 days since symptom onset or diagnosis and the culture positivity rate rapidly declined hereafter. This systematic review provides an overview of current evidence on the daily SARS-CoV-2 culture positivity rates during the post-vaccination period. These findings could be used to estimate the effectiveness of public health control measures, including treatment and preventive strategies, to reduce the spread of COVID-19.

Epidemiology and clinical features of SARS-CoV-2 infection in children and adolescents in the pre-Omicron era: A global systematic review and meta-analysis.

Methods: We searched MEDLINE, Embase, Global Health, CINAHL, China National Knowledge Infrastructure, Wanfang, CQvip, and the World Health Organization (WHO) COVID-19 global literature databases for primary studies recruiting children aged ≤18 years with a diagnosis of SARS-CoV-2 infection confirmed either by molecular or antigen tests. We used the Joanna Briggs Institute critical appraisal tools to appraise the study quality and conducted meta-analyses using the random effects model for all outcomes except for race/ethnicity as risk factors of SARS-CoV-2 infection. Results: We included 237 studies, each reporting at least one of the study outcomes. Based on data from 117 studies, the pooled SARS-CoV-2 positivity rate was 9.30% (95% confidence interval (CI) = 7.15-11.73). Having a comorbidity was identified as a risk factor for SARS-CoV-2 infection (risk ratio (RR) = 1.33; 95% CI = 1.04-1.71) based on data from 49 studies. Most cases in this review presented with mild disease (n = 50; 52.47% (95% CI = 44.03-60.84)). However, 20.70% of paediatric SARS-CoV-2 infections were hospitalised (67 studies), 7.19% required oxygen support (57 studies), 4.26% required intensive care (93 studies), and 2.92% required assisted ventilation (63 studies). The case fatality ratio (n = 119) was 0.87% (95% CI = 0.54-1.28), which included in-hospital and out-of-hospital deaths. Conclusions: Our data showed that children were at risk for SARS-CoV-2 infections and severe outcomes in the pre-Omicron era. These findings underscore the need for effective vaccination strategies for the paediatric population to protect against the acute and long-term sequelae of COVID-19. Registration: PROSPERO: CRD42022327680.

Definition and measurement of post-COVID-19 conditions in real-world practice: a global systematic literature review.

Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review summarises the heterogeneous methodology used to measure PCC across real-world studies and highlights trends by region, age group, PCC follow-up period and data source. METHODS: Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022. FINDINGS: Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to <6 months (39.2%), followed by 6 to <12 months (27.5%) and <3 months (22.9%). When classified by organ/system, constitutional-related PCC were the most frequently assessed in adult (86%) and paediatric (87%) populations. Within constitutional symptoms, fatigue was most frequently assessed in adult (91.6%) and paediatric (95.0%) populations, followed by fever/chills (37.9% and 55%, respectively). CONCLUSIONS: PCC definitions are heterogenous across real-world studies, which limits reliable comparisons between studies. However, some similarities were observed in terms of the most frequently measured PCC-associated symptoms/conditions, which may aid clinical management of patients with PCC.CRD42022376111.

Descriptive analysis to assess seasonal patterns of COVID-19 and influenza in low-income and middle-income countries in Asia, the Middle East and Latin America.

OBJECTIVES: Understanding disease seasonality can help predict the occurrence of outbreaks and inform public health planning. Respiratory diseases typically follow seasonal patterns; however, knowledge regarding the seasonality of COVID-19 and its impact on the seasonality of influenza remains limited. The objective of this study was to provide more evidence to understand the circulation of SARS-CoV-2, the virus responsible for COVID-19, in an endemic scenario to guide potential preventive strategies. DESIGN: In this study, a descriptive analysis was undertaken to describe seasonality trends and/or overlap between COVID-19 and influenza in 12 low-income and middle-income countries using Our World in Data and FluMart data sources. Plots of COVID-19 and influenza cases were analysed. SETTING: Singapore, Thailand, Malaysia, the Philippines, Argentina, Brazil, Mexico, South Africa, Morocco, Bahrain, Qatar and Saudi Arabia. OUTCOME MEASURES: COVID-19 cases and influenza cases. RESULTS: No seasonal patterns of SARS-CoV-2 or SARS-CoV-2/influenza cocirculation were observed in most countries, even when considering the avian influenza pandemic period. CONCLUSIONS: These results can inform public health strategies. The lack of observed seasonal behaviour highlights the importance of maintaining year-round vaccination rather than implementing seasonal campaigns. Further research investigating the influence of climate conditions, social behaviour and year-round preventive measures could be fundamental for shaping appropriate policies related to COVID-19 and respiratory viral disease control in low-income and middle-income countries as COVID-19 variant data and epidemiologic patterns accrue over time.

Prevalence of Adult Type 2 Diabetes Mellitus and Related Complications in Alberta, Canada: A Retrospective, Observational Study Using Administrative Data.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease and a leading cause of morbidity/mortality in Canada. We evaluated the burden of T2DM in Alberta, Canada, by estimating the 5-year period prevalence of T2DM and rates of comorbidities and complications/conditions after T2DM. METHODS: We conducted a population-based, retrospective study linking administrative health databases. Individuals with T2DM (≥18 years of age) were identified between 2008-2009 and 2018-2019 using a published algorithm, with follow-up data to March 2020. The 5-year period prevalence was estimated for 2014-2015 to 2018-2019. Individuals with newly identified T2DM, ascertained between 2010-2011 and 2017-2018 with a lookback period between 2008-2009 and 2009-2010 and a minimum 1 year of follow-up data, were evaluated for subsequent cardiovascular, diabetic, renal, and other complication/condition frequencies (%) and rates (per 100 person-years). Complications/conditions were stratified by atherosclerotic cardiovascular disease (ASCVD) status at index and age. RESULTS: The 5-year period prevalence of T2DM was 11,051 per 100,000 persons, with the highest prevalence in men 65 to <75 years of age. There were 195,102 individuals included in the cohort (mean age 56.7±14.7 years). The most frequently reported complications/conditions (rates per 100 person-years) were acute infection (23.10, 95% confidence interval [CI] 23.00 to 23.30), hypertension (17.30, 95% CI 16.80 to 17.70), and dyslipidemia (12.20, 95% CI 11.90 to 12.40). Individuals who had an ASCVD event/procedure and those ≥75 years of age had higher rates of complications/conditions. CONCLUSIONS: We found that over half of the individuals had hypertension or infection after T2DM. Also, those with ASCVD had higher rates of complications/conditions. Strategies to mitigate complications/conditions after T2DM are required to reduce the burden of this disease on individuals and health-care systems.

Modelling the Potential Public Health Impact of Different COVID-19 Vaccination Strategies with an Adapted Vaccine in Singapore.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has been a dynamically changing virus, requiring the development of adapted vaccines. This study estimated the potential public health impact alternative vaccination strategies for COVID-19 in Singapore. RESEARCH DESIGN AND METHODS: The outcomes of alternative vaccination strategies with a future adapted vaccine were estimated using a combined Markov decision tree model. The population was stratified by high- and standard-risk. Using age-specific inputs informed by local surveillance data and published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. RESULTS: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 278,614 cases 21,558 hospitalizations, 239 deaths, Singapore dollars (SGD) 277 million in direct medical costs, and SGD 684 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (3%), hospitalizations (29%), infections (145%), direct costs (90%), and indirect costs (192%) compared to the base case. CONCLUSIONS: Broader vaccination strategies using an adapted booster vaccine could have substantial public health and economic impact in Singapore.

Incidence and outcome of SARS-CoV-2 reinfection in the pre-Omicron era: A global systematic review and meta-analysis.

Background: With the emergence of new variants and sub-lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reinfections can significantly impact herd immunity, vaccination policies, and decisions on other public health measures. We conducted a systematic review and meta-analysis to synthesise the global evidence on SARS-CoV-2 reinfections in the pre-Omicron era. Methods: We searched five global databases (MEDLINE, Embase, CINAHL Plus, Global Health, WHO COVID-19) on 12 May 2022 and 28 July 2023 and three Chinese databases (CNKI, Wanfang, CQvip) on 16 October 2022 for articles reporting incidence and outcomes of SARS-CoV-2 reinfection before the period of Omicron (B.1.1.529) predominance. We assessed risk of bias using Joanna Briggs Institute critical appraisal tools and conducted meta-analyses with random effects models to estimate the proportion of SARS-CoV-2 reinfection among initially infected cases and hospitalisation and mortality proportions among reinfected ones. Results: We identified 7593 studies and extracted data from 64 included ones representing 21 countries. The proportion of SARS-CoV-2 reinfection was 1.16% (95% confidence interval (CI) = 1.01-1.33) based on 11 639 247 initially infected cases, with ≥45 days between the two infections. Healthcare providers (2.28%; 95% CI = 1.37-3.40) had a significantly higher risk of reinfection than the general population (1.00%; 95% CI = 0.81-1.20), while young adults aged 18 to 35 years (1.01%; 95% CI = 0.8-1.25) had a higher reinfection burden than other age groups (children <18 years old: 0.57%; 95% CI = 0.39-0.79, older adults aged 36-65 years old: 0.53%; 95% CI = 0.41-0.65, elderly >65 years old: 0.37%; 95% CI = 0.15-0.66). Among the reinfected cases, 8.12% (95% CI = 5.30-11.39) were hospitalised, 1.31% (95% CI = 0.29-2.83) were admitted to the intensive care unit, and 0.71% (95% CI = 0.02-2.01) died. Conclusions: Our data suggest a relatively low risk of SARS-CoV-2 reinfection in the pre-Omicron era, but the risk of hospitalisation was relatively high among the reinfected cases. Considering the possibility of underdiagnosis, the reinfection burden may be underestimated. Registration: PROSPERO: CRD42023449712.

Severe Hypoglycaemia in an Elderly Patient With Alzheimer's Dementia and Type 2 Diabetes Mellitus: A Case Report.

A 78-year-old diabetic patient was admitted with unexplained refractory hypoglycaemia. He was taking gliclazide and metformin and had good glycaemic control. He was suspected to have a sulfonylurea overdose, and intravenous 10% dextrose failed to correct hypoglycaemia. He was then treated with octreotide (a specific antidote to sulfonylurea), which corrected his low blood sugar level. Intravenous dextrose and octreotide are often the drugs of choice for treating hypoglycaemia from sulfonylurea toxicity. A high index of suspicion is needed for early diagnosis of sulfonylurea overdose.

Refractory Hypotension in an 80-Year-Old Man: A Case Report.

This case report presents the management and diagnosis of an 80-year-old gentleman who presented to the Accident and Emergency Department with refractory hypotension, hypoglycemia, and hyponatremia. Initially diagnosed with sepsis and cellulitis, it was later discovered that the patient was suffering from an Addisonian crisis due to adrenal insufficiency induced by long-term steroid use for rheumatoid arthritis. Prompt administration of intravenous hydrocortisone and fluid resuscitation led to a significant improvement in the patient's condition. This case emphasizes the importance of considering adrenal insufficiency in patients with similar clinical presentations and highlights the critical role of early diagnosis and treatment.

Modelling the potential public health impact of different vaccination strategies with an omicron-adapted bivalent vaccine in Thailand.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has continuously evolved, requiring the development of adapted vaccines. This study estimated the impact of the introduction and increased coverage of an Omicron-adapted bivalent booster vaccine in Thailand. RESEARCH DESIGN AND METHODS: The outcomes of booster vaccination with an Omicron-adapted bivalent vaccine versus no booster vaccination were estimated using a combined cohort Markov decision tree model. The population was stratified into high- and standard-risk subpopulations. Using age-specific inputs informed by published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. RESULTS: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 97,596 cases 36,578 hospitalizations, 903 deaths, THB 3,119 million in direct medical costs, and THB 10,589 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (95%), hospitalizations (512%), infections (782%), direct costs (550%), and indirect costs (687%) compared to the base case. CONCLUSIONS: Broader vaccination with an Omicron-adapted bivalent booster vaccine could have significant public health and economic benefits in Thailand.