Unveiling HPV's hidden link: Cardiovascular diseases and the viral intrigue.

Cardiovascular diseases (CVD) remain a major global health challenge, with an escalating impact on mortality despite advancements in managing conventional risk factors. This review investigates the intricate relationship between human papillomavirus (HPV) and CVD, shedding light on a novel aspect of cardiovascular health. Despite significant progress in understanding and managing traditional CVD risk factors, a substantial proportion of CVD cases lack these conventional markers. Recent research has unveiled HPV, a prevalent sexually transmitted infection, as a potential unconventional risk factor for CVD. This review delves into the underlying mechanisms linking HPV to CVD pathogenesis. HPV's influence on vascular endothelium and induction of systemic inflammation are key contributors. Additionally, HPV disrupts host lipid metabolism, further exacerbating the development of atherosclerosis. The link between HPV and CAD is not merely correlative; it encompasses a complex interplay of virological, immunological, and metabolic factors. Understanding the connection between HPV and CVD holds transformative potential. Insights from this review not only underscore the significance of considering HPV as a crucial risk factor but also advocate for targeted HPV screening and vaccination strategies to mitigate CVD risks. This multidisciplinary exploration bridges the gap between infectious diseases and cardiovascular health, emphasizing the need for a comprehensive approach to combating the global burden of cardiovascular disease. Further research and clinical guidelines in this realm are essential to harness the full scope of preventive and therapeutic interventions, ultimately shaping a healthier cardiovascular landscape.

Refining the provider payment system of India's government-funded health insurance programme: an econometric analysis.

OBJECTIVES: Reimbursement rates in national health insurance schemes are frequently weighted to account for differences in the costs of service provision. To determine weights for a differential case-based payment system under India's publicly financed national health insurance scheme, the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (PM-JAY), by exploring and quantifying the influence of supply-side factors on the costs of inpatient admissions and surgical procedures. DESIGN: Exploratory analysis using regression-based cost function on data from a multisite health facility costing study-the Cost of Health Services in India (CHSI) Study. SETTING: The CHSI Study sample included 11 public sector tertiary care hospitals, 27 public sector district hospitals providing secondary care and 16 private hospitals, from 11 Indian states. PARTICIPANTS: 521 sites from 57 healthcare facilities in 11 states of India. INTERVENTIONS: Medical and surgical packages of PM-JAY. PRIMARY AND SECONDARY OUTCOME MEASURES: The cost per bed-day and cost per surgical procedure were regressed against a range of factors to be considered as weights including hospital location, presence of a teaching function and ownership. In addition, capacity utilisation, number of beds, specialist mix, state gross domestic product, State Health Index ranking and volume of patients across the sample were included as variables in the models. Given the skewed data, cost variables were log-transformed for some models. RESULTS: The estimated mean costs per inpatient bed-day and per procedure were 2307 and 10 686 Indian rupees, respectively. Teaching status, annual hospitalisation, bed size, location of hospital and average length of hospitalisation significantly determine the inpatient bed-day cost, while location of hospital and teaching status determine the procedure costs. Cost per bed-day of teaching hospitals was 38-143.4% higher than in non-teaching hospitals. Similarly, cost per bed-day was 1.3-89.7% higher in tier 1 cities, and 19.5-77.3% higher in tier 2 cities relative to tier 3 cities, respectively. Finally, cost per surgical procedure was higher by 10.6-144.6% in teaching hospitals than non-teaching hospitals; 12.9-171.7% higher in tier 1 cities; and 33.4-140.9% higher in tier 2 cities compared with tier 3 cities, respectively. CONCLUSION: Our study findings support and validate the recently introduced differential provider payment system under the PM-JAY. While our results are indicative of heterogeneity in hospital costs, other considerations of how these weights will affect coverage, quality, cost containment, as well as create incentives and disincentives for provider and consumer behaviour, and integrate with existing price mark-ups for other factors, should be considered to determine the future revisions in the differential pricing scheme.

Impact of India's publicly financed health insurance scheme on public sector district hospitals: a health financing perspective.

Background: Districts hospitals in India play a pivotal role in delivering health care services in the public sector and are empanelled under India's national health insurance scheme i.e. Ayushman Bharat Pradhan Mantri Jan Aarogya Yojana (PMJAY). In this paper, we evaluate the extent to which the PMJAY impacts the district hospitals from a financing perspective. Methods: We used cost data from India's nationally representative costing study-'Costing of Health Services in India' (CHSI) to determine the incremental cost of treating PMJAY patients, after adjusting for resources that are paid through supply-side government financing route. Second, we used data on number and claim value paid to public district and sub-district hospitals during 2019, to determine the additional revenue generated through PMJAY. The annual net financial gain per district hospital was estimated as the difference between payments under PMJAY, and the incremental cost of delivering the services. Findings: At current levels of utilisation, the district hospitals in India gain a net annual financial benefit of $ 26.1 (₹ 1839.3) million, which can potentially increase up to $ 41.8 (₹ 2942.9) million with an increase in the share of patient volume. For an average district hospital, we estimate net annual financial gain of $ 169,607 (₹ 11.9 million), increasing up to $ 271,372 (₹ 19.1 million) per hospital with increased utilisation. Interpretation: Demand-side financing mechanisms can be used to strengthen the public sector. Increasing utilisation of district hospitals, by either gatekeeping or improving availability of services will enhance financial gains for district hospitals and strengthen public sector. Funding: Department of Health Research, Ministry of Health & Family Welfare, Government of India.

Cost-Effectiveness of the First Line Treatment Options For Metastatic Renal Cell Carcinoma in India.

PURPOSE: Tyrosine kinase inhibitors such as sunitinib and pazopanib are the mainstay of treatment of metastatic renal cell carcinoma (mRCC) in India. However, pembrolizumab and nivolumab have shown significant improvement in the median progression-free survival and overall survival among patients with mRCC. In this study, we aimed to determine the cost-effectiveness of the first-line treatment options for the patients with mRCC in India. METHODS: A Markov state-transition model was used to measure the lifetime costs and health outcomes associated with sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab among patients with first-line mRCC. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost-effectiveness using a willingness to pay threshold of one-time per capita gross-domestic product of India. The parameter uncertainty was analyzed using the probabilistic sensitivity analysis. RESULTS: We estimated the total lifetime cost per patient of ₹ 0.27 million ($3,706 US dollars [USD]), ₹ 0.35 million ($4,716 USD), ₹ 9.7 million ($131,858 USD), and ₹ 6.7 million ($90,481 USD) for the sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab arms, respectively. Similarly, the mean QALYs lived per patient were 1.91, 1.86, 2.75, and 1.97, respectively. Sunitinib incurs an average cost of ₹ 143,269 ($1,939 USD) per QALY lived. Therefore, sunitinib at current reimbursement rates (₹ 10,000 per cycle) has a 94.6% probability of being cost-effective at a willingness to pay threshold of 1-time per capita gross-domestic product (₹ 168,300) in the Indian context. CONCLUSION: Our findings support the current inclusion of sunitinib under India's publicly financed health insurance scheme.

Establishing a Health Technology Assessment Evidence Ecosystem in India's Pradhan Mantri Jan Arogya Yojana.

The introduction of the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (AB PM-JAY) scheme in India was a significant step toward universal health coverage. The PM-JAY scheme has made notable progress since its inception, including increasing the number of people covered and expanding the range of services provided under the health benefit package (HBP). The creation of the Health Financing and Technology Assessment (HeFTA) unit within the National Health Authority (NHA) further enhanced evidence-based decision-making processes. We outline the journey of HeFTA and highlight significant cost savings to the PM-JAY as a result of health technology assessment (HTA). Our paper also discusses the application of HTA evidence for decisions related to inclusions or exclusions in HBP, framing standard treatment guidelines as well as other policies. We recommend that future financing reforms for strategic purchasing should strengthen strategic purchasing arrangements and adopt value-based pricing (VBP). Integrating HTA and VBP is a progressive approach toward health care financing reforms for large government-funded schemes like the PM-JAY.

Cost of hospital services in India: a multi-site study to inform provider payment rates and Health Technology Assessment.

The 'Cost of Health Services in India (CHSI)' is the first large scale multi-site facility costing study to incorporate evidence from a national sample of both private and public sectors at different levels of the health system in India. This paper provides an overview of the extent of heterogeneity in costs caused by various supply-side factors.A total of 38 public (11 tertiary care and 27 secondary care) and 16 private hospitals were sampled from 11 states of India. From the sampled facilities, a total of 327 specialties were included, with 48, 79 and 200 specialties covered in tertiary, private and district hospitals respectively. A mixed methodology consisting of both bottom-up and top-down costing was used for data collection. Unit costs per service output were calculated at the cost centre level (outpatient, inpatient, operating theatre, and ICU) and compared across provider type and geographical location.The unadjusted cost per admission was highest for tertiary facilities (₹ 5690, 75 USD) followed by private facilities (₹ 4839, 64 USD) and district hospitals (₹ 3447, 45 USD). Differences in unit costs were found across types of providers, resulting from both variations in capacity utilisation, length of stay and the scale of activity. In addition, significant differences in costs were found associated with geographical location (city classification).The reliance on cost information from single sites or small samples ignores the issue of heterogeneity driven by both demand and supply-side factors. The CHSI cost data set provides a unique insight into cost variability across different types of providers in India. The present analysis shows that both geographical location and the scale of activity are important determinants for deriving the cost of a health service and should be accounted for in healthcare decision making from budgeting to economic evaluation and price-setting.

Cost of Surgical Care at Public Sector District Hospitals in India: Implications for Universal Health Coverage and Publicly Financed Health Insurance Schemes.

BACKGROUND: In low- and middle-income countries (LMICs), provisioning for surgical care is a public health priority. Ayushman Bharat Pradhan Mantri-Jan Aarogya Yojana (AB PM-JAY) is India's largest national insurance scheme providing free surgical and medical care. In this paper, we present the costs of surgical health benefit packages (HBPs) for secondary care in public district hospitals. METHODS: The costs were estimated using mixed (top-down and bottom-up) micro-costing methods. In phase II of the Costing of Health Services in India (CHSI) study, data were collected from a sample of 27 district hospitals from nine states of India. The district hospitals were selected using stratified random sampling based on the district's composite development score. We estimated unit costs for individual services-outpatient (OP) visit, per bed-day in inpatient (IP) and intensive care unit (ICU) stays, and surgical procedures. Together, this was used to estimate the cost of 250 AB PM-JAY HBPs. RESULTS: At the current level of utilization, the mean cost per OP consultation varied from US$4.10 to US$2.60 among different surgical specialities. The mean unit cost per IP bed-day ranged from US$13.40 to US$35.60. For the ICU, the mean unit cost per bed-day was US$74. Further, the unit cost of HBPs varied from US$564 for bone tumour excision to US$49 for lid tear repair. CONCLUSIONS: Data on the cost of delivering surgical care at the level of district hospitals is of critical value for evidence-based policymaking, price-setting for surgical care and planning to strengthen the availability of high quality and cost-effective surgical care in district hospitals.

Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. METHODS: Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI] <150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. RESULTS: CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. CONCLUSIONS: In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

A Prospective Blinded Study Evaluating the Role of Endoscopic Ultrasound before Endoscopic Retrograde Cholangiopancreatography in the Setting of "Positive" Intraoperative Cholangiogram during Cholecystectomy.

During laparoscopic cholecystectomy, intraoperative cholangiography (IOC) is used to identify common bile duct (CBD) stones. In patients whose IOC is suspicious for stones, endoscopic retrograde cholangiopancreatography (ERCP) is the modality of choice for stone removal. However, IOC has a false positive rate of 30 to 60 per cent, and ERCP adverse events may occur in 11 per cent of patients. Endoscopic ultrasound (EUS) may serve as a noninvasive means of diagnosing suspected CBD stones. This study sought to assess the role of EUS in predicting the likelihood of choledocholithiasis at ERCP in patients found to have a positive IOC. This was a prospective blinded study of EUS before ERCP in patients with a positive IOC. Recruited subjects who underwent cholecystectomy and had an IOC with suspicion for obstruction were referred for ERCP within one month of their procedure. In patients with a positive IOC, EUS had a positive predictive value of 95 per cent in detecting choledocholithiasis. IOC with single or multiple filling defects more often correlated to the presence of CBD stones. At ERCP, choledocholithiasis was present in 65 per cent of patients who had an IOC suspicious for CBD stones. EUS should be used as a noninvasive method to correctly identify retained CBD stones in low-to-moderate risk patients with a positive IOC.

Role of balloon-assisted cholangioscopy in a multiethnic cohort to assess complex biliary disease (with videos).

BACKGROUND: Cholangioscopy is used to diagnose and treat various biliary lesions. Balloon-assisted cholangioscopy (BAC) has mostly been reported in Asian patients with large bile ducts. OBJECTIVE: To assess the feasibility and accuracy of performing BAC in complex biliary diseases in Australian patients. DESIGN: Prospective observational study. SETTING: A single Australian tertiary referral hospital. PATIENTS: Fifty-nine consecutive patients (55 non-Asian ethnicity). INTERVENTIONS: BAC using ultrathin endoscopes. MAIN OUTCOME MEASUREMENTS: Procedural success rates, diagnostic accuracy, and adverse event rates. RESULTS: Fifty-nine patients underwent 76 BAC procedures for indeterminate biliary lesions, ampullary adenomas, and difficult stone disease. The technical success rate was 93%. The median bile duct diameter was 7 mm (range, 2-20). Of 34 indeterminate biliary strictures, 22 appeared benign and 12 malignant on BAC appearance alone. All benign-appearing strictures were confirmed benign, whereas 9 of 12 malignant-appearing strictures were confirmed malignant by biopsy sampling or follow-up (sensitivity 100% [95% CI, 66%-100%], specificity 88% [95% CI, 69%-97%], positive predictive value 75% [95% CI, 42%-93%], negative predictive value 100% [95% CI, 82%-100%]). BAC appearance correctly diagnosed indeterminate masses as benign (4/4) or malignant (3/3). Eight patients were assessed for bile duct extension of ampullary adenomas and 5 of 6 had biliary stones cleared directly or with holmium laser lithotripsy. Adequate histopathologic specimens were obtained from 31 of 39 (79%) attempted biopsy specimens. The adverse event rate was 8%. LIMITATIONS: A single-center, single endoscopist experience. CONCLUSIONS: In a largely non-Asian cohort with smaller bile ducts, BAC can be performed with high success and acceptable adverse event rates. BAC is particularly useful in differentiating benign from malignant indeterminate biliary lesions.

Characterisation of the cytokine milieu associated with the up-regulation of IL-6 and suppressor of cytokine 3 in chronic hepatitis C treatment non-responders.

BACKGROUND & AIMS: In chronic hepatitis C virus infection (CHC), expression of suppressor of cytokine signalling-3 (SOCS3) has been shown to be associated with obesity and non-response to antiviral therapy. In this study, we aimed to determine the effect of SOCS3 induction on the cytokine response in patients receiving Pegylated interferon (PegIFN) and ribavirin (RBV) therapy. METHODS: Peripheral blood mononuclear cells (PBMC) collected at baseline and at 12 weeks from CHC patients receiving PegIFN/RBV therapy were examined for mRNA and protein SOCS3 expression. Immunological assays were employed to examine cytokine production. RESULTS: There was increased expression of SOCS3 in PBMC of non-responders at week 12 of therapy, when compared to treatment responders (P = 0.0001). The expression of SOCS3 correlated with body mass index (BMI) (r = 0.54; P = 0.01). Patients with low SOCS3 expression at week 12 of therapy had lower HCV-specific IFN-γ production in enzyme-linked immunosorbent spot (ELISpot) assays (P = 0.01), and reduced ex-vivo production of the anti-HCV effector cytokines interleukin (IL)-2 and tumour necrosis factor (TNF)-α(P = 0.01 and P = 0.04 respectively). Analysis of serum cytokine levels revealed higher levels of IL-6 at week 12 in the high SOCS3 expression group (P = 0.02) while IL-6 levels correlated with SOCS3 expression in the entire cohort (P = 0.04). Ex-vivo studies confirmed that IL-6 induced SOCS3, and neutralisation of IL-6 reduced levels of SOCS3. CONCLUSION: In subjects with increased BMI and non-response to antiviral therapy, the IL-6/SOCS3 axis appears to play a crucial role in altering the anti-HCV-cytokine response associated with antiviral therapy.