Restoration of endodontically treated teeth: A cost-effectiveness analysis of an endocrown versus a complete crown.

STATEMENT OF PROBLEM: Endocrowns have been proposed as an alternative to post-and-core retained complete crowns for structurally compromised endodontically treated teeth. However, an analysis of their cost-effectiveness is lacking. PURPOSE: The purpose of this simulation study was to assess the cost-effectiveness of an endocrown versus a complete crown as a definitive restoration for structurally compromised endodontically treated teeth. MATERIAL AND METHODS: A Markov simulation model was constructed with endodontically treated permanent molar teeth using TreeAge Pro Healthcare (2023) as a starting point for an 18-year-old patient. Costs were extrapolated from the ADA dental survey based on the United States healthcare, and the probabilities of transition were derived from existing literature. The cost-effectiveness was determined by using Monte Carlo microsimulations. A sensitivity analysis was performed to validate the model internally, whereas an experienced health expert and an endodontist performed the face validation. RESULTS: The complete crown was associated with additional health benefits (1.36 and 0.9 more years over a period of 5 years and lifetime, respectively) but at an increased cost (an additional 1143 USD and 1535 USD over a period of 5 years and lifetime, respectively). Moreover, the endocrown was cost-effective at lower Willingness-To-Pay (WTP) values (92% acceptable at 250 USD for 5 years and 73% acceptable at 250 USD for the lifetime of an individual), whereas at increased WTP threshold values, the complete crown was a cost-effective restoration (98.6% acceptable at 1250 USD for 5 years and 99.5% acceptable at 8000 USD over an individual's lifetime). CONCLUSIONS: The endocrown was a cost-effective restorative option at lower WTP values. However, at an increased WTP threshold, the complete crown became a more cost-effective restoration.

Irreversible pulpitis in mature permanent teeth: a cost-effectiveness analysis of pulpotomy versus root canal treatment.

INTRODUCTION: Evidence-based dentistry suggests pulpotomy as a potential alternative to root canal treatment in mature permanent teeth with irreversible pulpitis. However, the evidence surrounding the cost-valuation and cost-efficacy of this treatment modality is not yet established. In this context, we adopted an economic modeling approach to assess the cost-effectiveness of pulpotomy versus root canal treatment, as this could aid in effective clinical decision-making. METHODS: A Markov model was constructed following a mature permanent tooth with irreversible pulpitis in an 18-year-old patient over a lifetime using TreeAge Pro Healthcare 2022. Transition probabilities were estimated based on existing literature. Costs were estimated based on the United States healthcare following a private-payer perspective and parameter uncertainties were addressed using Monte-Carlo simulations. The model was validated internally by sensitivity analyses, and face validation was performed by an experienced endodontist and health economist. RESULTS: In the base case scenario, root canal treatment was associated with additional health benefit but at an increased cost (1.08 more years with an incremental cost of 311.20 USD) over a period of an individual's lifetime. The probabilistic sensitivity analysis revealed pulpotomy to be cost-effective at lower Willingness-To-Pay (WTP) values (99.9% acceptable at 50 USD) whereas increasing the values of WTP threshold root canal treatment was a cost-effective treatment (99.9% acceptable at 550 USD). CONCLUSION: Based on current evidence, pulpotomy was a cost-effective treatment option at lower WTP values for the management of irreversible pulpitis in mature permanent teeth. However, by increasing the WTP threshold, root canal treatment became a more cost-effective treatment option over a period of lifetime of an individual.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Exploring the Access and Use of Social Technologies by Older Adults in Support of Their Mental Health During the COVID-19 Pandemic: A Rapid Review.

Coronavirus disease (COVID-19) lockdowns disproportionately affect older people where most suffer from social isolation and loneliness, which translate into higher rates of depression and anxiety. This study aimed to explore the accessibility, outcomes, and challenges of social technology use among community-dwelling older adults, older adults in long-term care, older adults with neurocognitive disorder, and older adults with pre-frailty and frailty, to help guide future research in this area. A rapid review was conducted, and articles were retrieved from four online databases, including Medline, AgeLine, EconLit and CINAHL, and grey literature from Google Scholar. Of the 131 articles retrieved, 24 were included in this review. The positive outcomes of social technology use include improved mental and physical health, reduced health disparities, and increased autonomy. Adverse outcomes include furthering the digital divide. More research surrounding the economic impacts of social technologies is warranted.

Cost-effectiveness analysis of Smart Triage, a data-driven pediatric sepsis triage platform in Eastern Uganda.

BACKGROUND: Sepsis, characterized by organ dysfunction due to presumed or proven infection, has a case-fatality over 20% in severe cases in low-and-middle income countries. Early diagnosis and treatment have proven benefits, prompting our implementation of Smart Triage at Jinja Regional Referral Hospital in Uganda, a program that expedites treatment through a data-driven triage platform. We conducted a cost-effectiveness analysis of Smart Triage to explore its impact on patients and inform multicenter scale up. METHODS: The parent clinical trial for Smart Triage was pre-post in design, using the proportion of children receiving sepsis treatment within one hour as the primary outcome, a measure linked to mortality benefit in existing literature. We used a decision-analytic model with Monte Carlo simulation to calculate the cost per year-of-life-lost (YLL) averted of Smart Triage from societal, government, and patient perspectives. Healthcare utilization and lost work for seven days post-discharge were translated into costs and productivity losses via secondary linkage data. RESULTS: In 2021 United States dollars, Smart Triage requires an annuitized program cost of only $0.05 per child, but results in $15.32 saved per YLL averted. At a willingness-to-pay threshold of only $3 per YLL averted, well below published cost-effectiveness threshold estimates for Uganda, Smart Triage approaches 100% probability of cost-effectiveness over the baseline manual triage system. This cost-effectiveness was observed from societal, government, and patient perspectives. The cost-effectiveness observed was driven by a reduction in admission that, while explainable by an improved triage mechanism, may also be partially attributable to changes in healthcare utilization influenced by the coronavirus pandemic. However, Smart Triage remains cost-effective in sensitivity analyses introducing a penalty factor of up to 50% in the reduction in admission. CONCLUSION: Smart Triage's ability to both save costs and avert YLLs indicates that patients benefit both economically and clinically, while its high probability of cost-effectiveness strongly supports multicenter scale up. Areas for further research include the incorporation of years lived with disability when sepsis disability weights in low-resource settings become available and analyzing budget impact during multicenter scale up. TRIAL REGISTRATION: NCT04304235 (registered on 11/03/2020, clinicaltrials.gov).

Molecular mechanism of antimicrobial co-resistance Colistin (mcr-1) and ESBLs genes among Escherichia coli isolates from commercial chickens in Pakistan.

Emergence of plasmid mediated colistin and extended spectrum ß-lactamases (ESBL) resistant genes has been impacted the efficacy of colistin and ß-lactams drugs like 3rd, 4th generation cephalosporin. Current study was aimed to investigate antimicrobial resistance genes (ARGs) among Escherichia coli isolates from meat producing commercial broilers in Pakistan. Two hundred (n=200) fecal samples were collected during January-2018 to August-2019. For isolation of E. coli, pink colonies on MacConkey agar were transferred to EMB agar. Metallic sheen color colonies were tested biochemically using API-20E kit. The molecular identification of E. coli (n=153) was targeted by amplification of uid gene through polymerase chain reaction (PCR) and different ARGs i.e. gentamicin, streptomycin, tetracycline, colistin, ß-lactams drugs, quinolone and ampicillin followed by sequence analysis. Genotypically, followed by phenotypically of resistant ARGs of isolated PCR-confirmed E. coli (153) shoed resistant against gentamicin (aac(3)-IV), streptomycin (aadA1), tetracycline (tetA), colistine (mcr-1), ampicillin (bla-TEM) and bla-CTX-M were 86%, 88%, 86%, 88%, 83% & 77% respectively. 33/38 (86%) of the isolate was positive for quinolone resistance. Colistine (mcr-1), ESBLs (bla-TEM) and (bla-CTX-M) resistance genes were 88%, 83% and 77% respectively. About 33 isolated E. coli harbored the both mcr-1 and ESBLs genes. All of E. coli isolates were found sensitive to ceftriaxone (CTX-30) and imipenem (IMP-10). The Isolated E. coli showed single or multi clade decadency. The E. coli and ARGs sequences showed single or multi clade decadency. This is first comprehensive study from Pakistan that described the molecular evidences of ARGs and their co-existence in single isolates originated from commercial poultry. Commercial chicken (Broilers) can act as melting pot of antibiotic resistance genes for human being. It is alarming situation for surveillance of antibiotic resistance program because of more regulated prescription of antimicrobial agents in Pakistan.

Association of dementia and patient outcomes among COVID-19 patients: A multi-center retrospective case-control study.

Background: We conducted a retrospective cohort study on COVID-19 patients with and without dementia by extracting data from the HCA Healthcare Enterprise Data Warehouse between January-September 2020. Aims: To describe the role of patients' baseline characteristics specifically dementia in determining overall health outcomes in COVID-19 patients. Methods: We grouped in-patients who had ICD-10 codes for dementia (DM) with age and gender-matched (1:2) patients without dementia (ND). Our primary outcome variables were in-hospital mortality, length of stay, Intensive Care Unit (ICU) admission, ICU-free days, mechanical ventilation (MV) use, MV-free days and 90-day re-admission. Results: Matching provided similar age and sex in DM and ND groups. BMI (median, 25.8 vs. 27.6) and proportion of patients who had smoked (23.3 vs. 31.3%) were lower in DM than in ND patients. The median (IQR) Elixhauser Comorbidity Index was higher in dementia patients 7 (5-10) vs. 5 (3-7, p < 0.01). Higher mortality was observed in DM group (30.8%) vs. ND group (26.4%, p < 0.01) as an unadjusted univariate analysis. The 90-day readmission was not different (32.1 vs. 31.8%, p = 0.8). In logistic regression analysis, the odds of dying were not different between patients in DM and ND groups (OR = 1.0; 95% CI 0.86-1.17), but the odds of ICU admissions were significantly lower for dementia patients (OR = 0.58, 95% CI 0.51-0.66). Conclusions: Our data showed that COVID-19 patients with dementia did not fare substantially worse, but in fact, fared better when certain metrics were considered.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer.

Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Cost-effectiveness analysis protocol of the Smart Triage program: A point-of-care digital triage platform for pediatric sepsis in Eastern Uganda.

BACKGROUND: Sepsis is a clinical syndrome characterized by organ dysfunction due to presumed or proven infection. Severe cases can have case fatality ratio 25% or higher in low-middle income countries, but early diagnosis and timely treatment have a proven benefit. The Smart Triage program in Jinja Regional Referral Hospital in Uganda will provide expedited sepsis treatment in children through a data-driven electronic patient triage system. To complement the ongoing Smart Triage interventional trial, we propose methods for a concurrent cost-effectiveness analysis of the Smart Triage platform. METHODS: We will use a decision-analytic model taking a societal perspective, combining government and out-of-pocket costs, as patients bear a sizeable portion of healthcare costs in Uganda due to the lack of universal health coverage. Previously published secondary data will be used to link healthcare utilization with costs and intermediate outcomes with mortality. We will model uncertainty via probabilistic sensitivity analysis and present findings at various willingness-to-pay thresholds using a cost-effectiveness acceptability curve. DISCUSSION: Our proposed analysis represents a first step in evaluating the cost-effectiveness of an innovative digital triage platform designed to improve clinical outcomes in pediatric sepsis through expediting care in low-resource settings. Our use of a decision analytic model to link secondary costing data, incorporate post-discharge healthcare utilization, and model clinical endpoints is also novel in the pediatric sepsis triage literature for low-middle income countries. Our analysis, together with subsequent analyses modelling budget impact and scale up, will inform future modifications to the Smart Triage platform, as well as motivate scale-up to the district and national levels. TRIAL REGISTRATION: Trial registration of parent clinical trial: NCT04304235, https://clinicaltrials.gov/ct2/show/NCT04304235. Registered 11 March 2020.

Economic and cost-effectiveness analysis of the Community-Level Interventions for Pre-eclampsia (CLIP) trials in India, Pakistan and Mozambique.

BACKGROUND: The Community-Level Interventions for Pre-eclampsia (CLIP) trials (NCT01911494) in India, Pakistan and Mozambique (February 2014-2017) involved community engagement and task sharing with community health workers for triage and initial treatment of pregnancy hypertension. Maternal and perinatal mortality was less frequent among women who received ≥8 CLIP contacts. The aim of this analysis was to assess the incremental costs and cost-effectiveness of the CLIP intervention overall in comparison to standard of care, and by PIERS (Pre-eclampsia Integrated Estimate of RiSk) On the Move (POM) mobile health application visit frequency. METHODS: Included were all women enrolled in the three CLIP trials who had delivered with known outcomes by trial end. According to the number of POM-guided home contacts received (0, 1-3, 4-7, ≥8), costs were collected from annual budgets and spending receipts, with inclusion of family opportunity costs in Pakistan. A decision tree model was built to determine the cost-effectiveness of the intervention (vs usual care), based on the primary clinical endpoint of years of life lost (YLL) for mothers and infants. A probabilistic sensitivity analysis was used to assess uncertainty in the cost and clinical outcomes. RESULTS: The incremental per pregnancy cost of the intervention was US$12.66 (India), US$11.51 (Pakistan) and US$13.26 (Mozambique). As implemented, the intervention was not cost-effective due largely to minimal differences in YLL between arms. However, among women who received ≥8 CLIP contacts (four in Pakistan), the probability of health system and family (Pakistan) cost-effectiveness was ≥80% (all countries). CONCLUSION: The intervention was likely to be cost-effective for women receiving ≥8 contacts in Mozambique and India, and ≥4 in Pakistan, supporting WHO guidance on antenatal contact frequency. TRIAL REGISTRATION NUMBER: NCT01911494.

An Overview of First 100 Cardiac Surgery Cases at a Newly Developed Satellite Center in Sukkur, Pakistan.

Introduction The aim of this research is to evaluate the in-hospital and early outcomes of the first 100 adult cardiac surgeries performed at a newly developed satellite center in Sukkur, Pakistan. Methods This is an audit of the first 100 adult cardiac surgeries performed at a newly developed satellite center of the National Institute of Cardiovascular Diseases (NICVD) at Sukkur, Pakistan, from March 2018 to November 2018 with 12 months of post-operative follow-up. Patients were offered off-pump coronary artery bypass (OPCAB), on-pump coronary artery bypass (ONCAB), mitral valve replacement (MVR), aortic valve replacement (AVR), minimally invasive cardiac surgery (MICS), and congenital adult congenital heart disease (ACHD) procedures by expert faculty of NICVD with a minimum of five years of post-fellowship experience. Results The mean age was 47.11 ± 14.6 years, with a male predominance of 77%. Hypertension and smoking were the most common risk factors that were observed in 32% and 33%, respectively, followed by diabetes and dyslipidemia with a frequency of 20% and 9%, respectively. The mean EuroSCORE (European System for Cardiac Operative Risk Evaluation) II for this patient cohort was 1.165 ± 0.50, with a maximum score of 2.3 in one patient. Out of 100 procedures, 51 were ONCAB, 19 were OPCAB, 16 were MVR, three were AVR, nine were ACHD, and two were MICS. Survival status post-operative as well as after one year was 100%. The frequency of post-operative bleeding was 7%, mean post-operative mechanical ventilation time was 213 ± 273 hours, and in-hospital stay was 5.41 ± 0.165 days. Lost to follow-up at one year was 4% (four). During the follow-up assessment, 39.5% of the patients had complained of mild-to-moderate intensity retrosternal pain and 4.2% had superficial surgical site infection of the sternal wound. A significant improvement in functional class was observed in 38.5% of patients, whereas 4.2% (four) had a significant drop in functional class post-operatively. Conclusion Providing tertiary care and early cardiac surgical facility to the people of Sukkur at their doorstep, in a newly developed satellite center, has resulted in improved outcomes, early quality treatment facility, and avoidance of long travel time.

Clinical Impact and Cost Efficacy of Newborn Screening for Congenital Adrenal Hyperplasia.

OBJECTIVES: To evaluate the clinical impact of a congenital adrenal hyperplasia (CAH) newborn screening program and incremental costs relative to benefits in screened vs unscreened infants. We hypothesized that screening would lead to clinical benefits and would be cost effective. STUDY DESIGN: This was an ambispective cohort study at British Columbia Children's Hospital, including infants diagnosed with CAH from 1988-2008 and 2010-2018. Data were collected retrospectively (unscreened cohort) and prospectively (screened cohort). Outcome measures included hospitalization, medical transport, and resuscitation requirements. The economic analysis was performed using a public payer perspective. RESULTS: Forty unscreened and 17 screened infants were diagnosed with CAH (47% vs 53% male). Median days to positive screen was 6 and age at diagnosis was 5 days (range, 0-30 days) and 6 days (range, 0-13 days) in unscreened and screened populations, respectively. In unscreened newborns, 55% required transport to a tertiary care hospital, 85% required hospitalization, and 35% required a fluid bolus compared with 29%, 29%, and 12% in screened infants, respectively. The cost of care was $33 770 per case in unscreened vs $17 726 in screened newborns. In the screened cohort, the incremental cost-effectiveness ratio was $290 in the best case analysis and $4786 in the base case analysis, per hospital day avoided. CONCLUSIONS: Compared with unscreened newborns, those screened for CAH were less likely to require medical transport and had shorter hospital stays. Screening led to a decrease in hospitalization costs. Although screening did not result in cost savings, it was assessed to be cost effective considering the clinical benefits and incremental cost-effectiveness ratio.

The feasibility of task-sharing the identification, emergency treatment, and referral for women with pre-eclampsia by community health workers in India.

BACKGROUND: Hypertensive disorders are the second highest direct obstetric cause of maternal death after haemorrhage, accounting for 14% of maternal deaths globally. Pregnancy hypertension contributes to maternal deaths, particularly in low- and middle-income countries, due to a scarcity of doctors providing evidence-based emergency obstetric care. Task-sharing some obstetric responsibilities may help to reduce the mortality rates. This study was conducted to assess acceptability by the community and other healthcare providers, for task-sharing by community health workers (CHW) in the identification and initial care in hypertensive disorders in pregnancy. METHODS: This study was conducted in two districts of Karnataka state in south India. A total of 14 focus group discussions were convened with various community representatives: women of reproductive age (N = 6), male decision-makers (N = 2), female decision-makers (N = 3), and community leaders (N = 3). One-to-one interviews were held with medical officers (N = 2), private healthcare OBGYN specialists (N = 2), senior health administrators (N = 2), Taluka (county) health officers (N = 2), and obstetricians (N = 4). All data collection was facilitated by local researchers familiar with the setting and language. Data were subsequently transcribed, translated and analysed thematically using NVivo 10 software. RESULTS: There was strong community support for home visits by CHW to measure the blood pressure of pregnant women; however, respondents were concerned about their knowledge, training and effectiveness. The treatment with oral antihypertensive agents and magnesium sulphate in emergencies was accepted by community representatives but medical practitioners and health administrators had reservations, and insisted on emergency transport to a higher facility. The most important barriers for task-sharing were concerns regarding insufficient training, limited availability of medications, the questionable validity of blood pressure devices, and the ability of CHW to correctly diagnose and intervene in cases of hypertensive disorders of pregnancy. CONCLUSION: Task-sharing to community-based health workers has potential to facilitate early diagnosis of the hypertensive disorders of pregnancy and assist in the provision of emergency care. We identified some facilitators and barriers for successful task-sharing of emergency obstetric care aimed at reducing mortality and morbidity due to hypertensive disorders of pregnancy.

Economic evaluation of Community Level Interventions for Pre-eclampsia (CLIP) in South Asian and African countries: a study protocol.

BACKGROUND: Globally, hypertensive disorders of pregnancy, particularly pre-eclampsia and eclampsia, are the leading cause of maternal and neonatal mortality, and impose substantial burdens on the families of pregnant women, their communities, and healthcare systems. The Community Level Interventions for Pre-eclampsia (CLIP) Trial evaluates a package of care applied at both community and primary health centres to reduce maternal and perinatal disabilities and deaths resulting from the failure to identify and manage pre-eclampsia at the community level. Economic evaluation of health interventions can play a pivotal role in priority setting and inform policy decisions for scale-up. At present, there is a paucity of published literature on the methodology of economic evaluation of large, multi-country, community-based interventions in the area of maternal and perinatal health. This study protocol describes the application of methodology for economic evaluation of the CLIP in South Asia and Africa. METHODS: A mixed-design approach i.e. cost-effectiveness analysis (CEA) and qualitative thematic analysis will be used alongside the trial to prospectively evaluate the economic impact of CLIP from a societal perspective. Data on health resource utilization, costs, and pregnancy outcomes will be collected through structured questionnaires embedded into the pregnancy surveillance, cross-sectional survey and budgetary reviews. Qualitative data will be collected through focus groups (FGs) with pregnant women, household male-decision makers, care providers, and district level health decision makers. The incremental cost-effectiveness ratio will be calculated for healthcare system and societal perspectives, taking into account the country-specific model inputs (costs and outcome) from the CLIP Trial. Emerging themes from FGs will inform the design of the model, and help to interpret findings of the CEA. DISCUSSION: The World Health Organization (WHO) strongly recommends cost-effective interventions as a key aspect of achieving Millennium Development Goal (MDG)-5 (i.e. 75 % reduction in maternal mortality from 1990 levels by 2015). To date, most cost-effectiveness studies in this field have focused specifically on the diagnostic and clinical management of pre-eclampsia, yet rarely on community-based interventions in low-and-middle-income countries (LMICs). This study protocol will be of interest to public health scientists and health economists undertaking community-based trials in the area of maternal and perinatal health, particularly in LMICs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01911494.

Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005-2013.

While pneumococcal conjugate vaccines have been implemented in most countries worldwide, use in Asia has lagged in part because of a lack of data on the amount of disease that is vaccine preventable in the region. We describe pneumococcal serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD) from 2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n = 81) of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years and n = 5 among adults). Serotypes were determined by target amplification of DNA extracted from pneumococcal isolates (n = 52) or CSF specimens (n = 59). Serogroup 18 was the most common serogroup causing meningitis in children <5 years, accounting for 21% of cases (n = 13). The 10-valent pneumococcal conjugate vaccine (PCV 10) or PCV10- related serotypes were found in 61% (n = 47) of childhood (age 0-15 years) meningitis episodes. PCV-13 increased this coverage to 63% (one additional serotype 19A; n = 48). Our data indicate that use of PCVs would prevent a large proportion of serious pneumococcal disease.

Stretch-activation of angiotensin II type 1a receptors contributes to the myogenic response of mouse mesenteric and renal arteries.

RATIONALE: Vascular wall stretch is the major stimulus for the myogenic response of small arteries to pressure. The molecular mechanisms are elusive, but recent findings suggest that G protein-coupled receptors can elicit a stretch response. OBJECTIVE: To determine whether angiotensin II type 1 receptors (AT1R) in vascular smooth muscle cells exert mechanosensitivity and identify the downstream ion channel mediators of myogenic vasoconstriction. METHODS AND RESULTS: We used mice deficient in AT1R signaling molecules and putative ion channel targets, namely AT1R, angiotensinogen, transient receptor potential channel 6 (TRPC6) channels, or several subtypes of the voltage-gated K+ (Kv7) gene family (KCNQ3, 4, or 5). We identified a mechanosensing mechanism in isolated mesenteric arteries and in the renal circulation that relies on coupling of the AT1R subtype a to a Gq/11 protein as a critical event to accomplish the myogenic response. Arterial mechanoactivation occurs after pharmacological block of AT1R and in the absence of angiotensinogen or TRPC6 channels. Activation of AT1R subtype a by osmotically induced membrane stretch suppresses an XE991-sensitive Kv channel current in patch-clamped vascular smooth muscle cells, and similar concentrations of XE991 enhance mesenteric and renal myogenic tone. Although XE991-sensitive KCNQ3, 4, and 5 channels are expressed in vascular smooth muscle cells, XE991-sensitive K+ current and myogenic contractions persist in arteries deficient in these channels. CONCLUSIONS: Our results provide definitive evidence that myogenic responses of mouse mesenteric and renal arteries rely on ligand-independent, mechanoactivation of AT1R subtype a. The AT1R subtype a signal relies on an ion channel distinct from TRPC6 or KCNQ3, 4, or 5 to enact vascular smooth muscle cell activation and elevated vascular resistance.

Haemoptysis in an intravenous drug user: injection needle impacted in the left main bronchus.

We report a case of a 35-year-old man who presented with 4-week history of haemoptysis, with a history of intravenous drug use. There was no other significant medical or surgical history and no recollection of any foreign body aspiration. Chest X-ray and CT scan showed 40 mm long needle in left main bronchus, partly lying outside the bronchus into the mediastinum. Flexible and rigid bronchoscopes proved to be unsuccessful in retrieving the needle. We proceeded with left posterolateral thoracotomy and the left main bronchus was explored to take out this 21-gauge (green) injection needle. The distal half of the needle with the sharp end was lying in the mediastinum piercing through the bronchial wall. Surgery was uneventful with good postoperative recovery and the patient was discharged 4 days later.

Inositol 1,4,5-trisphosphate (IP3) receptor up-regulation in hypertension is associated with sensitization of Ca2+ release and vascular smooth muscle contractility.

Resistance arteries show accentuated responsiveness to vasoconstrictor agonists in hypertension, and this abnormality relies partly on enhanced Ca(2+) signaling in vascular smooth muscle (VSM). Although inositol 1,4,5-triphosphate receptors (IP3Rs) are abundant in VSM, their role in the molecular remodeling of the Ca(2+) signaling machinery during hypertension has not been addressed. Therefore, we compared IP3R expression and function between mesenteric arteries of normotensive and hypertensive animals. Levels of IP3R transcript and protein were significantly increased in mesenteric arteries of hypertensive animals, and pharmacological inhibition of the IP3R revealed a higher contribution of IP3-dependent Ca(2+) release to vascular contraction in these arteries. Subsequently, we established cultured aortic VSM A7r5 cells as a cellular model that replicates IP3R up-regulation during hypertension by depolarizing the VSM cell membrane. IP3R up-regulation requires Ca(2+) influx through L-type Ca(2+) channels, followed by activation of the calcineurin-NFAT axis, resulting in IP3R transcription. Functionally, IP3R up-regulation in VSM is associated with enhancement and sensitization of IP3-dependent Ca(2+) release, resulting in increased VSM contraction in response to agonist stimulation.

Schools as potential vaccination venue for vaccines outside regular EPI schedule: results from a school census in Pakistan.

BACKGROUND: Vaccines are the most effective public health intervention. Expanded Program on Immunization (EPI) provides routine vaccination in developing countries. However, vaccines that cannot be given in EPI schedule such as typhoid fever vaccine need alternative venues. In areas where school enrolment is high, schools provide a cost effective opportunity for vaccination. Prior to start of a school-based typhoid vaccination program, interviews were conducted with staff of educational institutions in two townships of Karachi, Pakistan to collect baseline information about the school system and to plan a typhoid vaccination program. Data collection teams administered a structured questionnaire to all schools in the two townships. The administrative staff was requested information on school fee, class enrolment, past history of involvement and willingness of parents to participate in a vaccination campaign. RESULTS: A total of 304,836 students were enrolled in 1,096 public, private, and religious schools (Madrasahs) of the two towns. Five percent of schools refused to participate in the school census. Twenty-five percent of schools had a total enrolment of less than 100 students whereas 3% had more than 1,000 students. Health education programs were available in less than 8% of public schools, 17% of private schools, and 14% of Madrasahs. One-quarter of public schools, 41% of private schools, and 43% of Madrasahs had previously participated in a school-based vaccination campaign. The most common vaccination campaign in which schools participated was Polio eradication program. Cost of the vaccine, side effects, and parents' lack of information were highlighted as important limiting factors by school administration for school-based immunization programs. Permission from parents, appropriateness of vaccine-related information, and involvement of teachers were considered as important factors to improve participation. CONCLUSIONS: Health education programs are not part of the regular school curriculum in developing countries including Pakistan. Many schools in the targeted townships participated in immunization activities but they were not carried out regularly. In the wake of low immunization coverage in Pakistan, schools can be used as a potential venue not only for non-EPI vaccines, but for a catch up vaccination of routine vaccines.