Cancer Medicines: What Is Essential and Affordable in India?

PURPOSE The WHO essential medicines list (EML) guides selection of drugs for national formularies. Here, we evaluate which medicines are considered highest priority by Indian oncologists and the extent to which they are
available in routine practice. METHODS This is a secondary analysis of an electronic survey developed by the WHO EML Cancer Medicine Working Group. The survey was distributed globally using a hierarchical snowball method to physicians who prescribe systemic anticancer therapy. The survey captured the 10 medicines oncologists considered highest priority for population health and their availability in routine practice.
RESULTS The global study cohort included 948 respondents from 82 countries; 98 were from India and 67 were from other low- and middle-income countries. Compared with other low- and middle-income countries, the Indian cohort was more likely to be medical oncologist (70% v 31%, P , .001) and work exclusively in the private health system (52% v 17%, P , .001). 14/20 most commonly selected medicines were conventional
cytotoxic drugs. Universal access to these medicines was reported by a minority of oncologists; risks of significant out-of-pocket expenditures for each medicine were reported by 19%-58% of oncologists. Risk of catastrophic expenditure was reported by 58%-67% of oncologists for rituximab and trastuzumab. Risks of financial toxicity were substantially higher within the private health system compared with the public system.
CONCLUSION Most high-priority cancer medicines identified by Indian oncologists are generic chemotherapy agents that provide substantial improvements in survival and are already included in WHO EML. Access to these
treatments remains limited by major financial burdens experienced by patients. This is particularly acute within the private health system. Strategies are urgently needed to ensure that high-quality cancer care is affordable and accessible to all patients in India

Health-care-associated bloodstream and urinary tract infections in a network of hospitals in India: a multicentre, hospital-based, prospective surveillance study

Background
Health-care-associated infections (HAIs) cause significant morbidity and mortality globally, including in low-income and middle-income countries (LMICs). Networks of hospitals implementing standardised HAI surveillance can provide valuable data on HAI burden, and identify and monitor HAI prevention gaps. Hospitals in many LMICs use HAI case definitions developed for higher-resourced settings, which require human resources and laboratory and imaging tests that are often not available.

Methods
A network of 26 tertiary-level hospitals in India was created to implement HAI surveillance and prevention activities. Existing HAI case definitions were modified to facilitate standardised, resource-appropriate surveillance across hospitals. Hospitals identified health-care-associated bloodstream infections and urinary tract infections (UTIs) and reported clinical and microbiological data to the network for analysis.

Findings
26 network hospitals reported 2622 health-care-associated bloodstream infections and 737 health-care-associated UTIs from 89 intensive care units (ICUs) between May 1, 2017, and Oct 31, 2018. Central line-associated bloodstream infection rates were highest in neonatal ICUs (>20 per 1000 central line days). Catheter-associated UTI rates were highest in paediatric medical ICUs (4·5 per 1000 urinary catheter days). Klebsiella spp (24·8%) were the most frequent organism in bloodstream infections and Candida spp (29·4%) in UTIs. Carbapenem resistance was common in Gram-negative infections, occurring in 72% of bloodstream infections and 76% of UTIs caused by Klebsiella spp, 77% of bloodstream infections and 76% of UTIs caused by Acinetobacter spp, and 64% of bloodstream infections and 72% of UTIs caused by Pseudomonas spp.

Interpretation
The first standardised HAI surveillance network in India has succeeded in implementing locally adapted and context-appropriate protocols consistently across hospitals and has been able to identify a large number of HAIs. Network data show high HAI and antimicrobial resistance rates in tertiary hospitals, showing the importance of implementing multimodal HAI prevention and antimicrobial resistance containment strategies.

Funding
US Centers for Disease Control and Prevention cooperative agreement with All India Institute of Medical Sciences, New Delhi.

Translation
For the Hindi translation of the abstract see Supplementary Materials section.

Health-care-associated infection surveillance in India

Health-care-associated infections (HAIs) are the infections acquired while patients receive treatment for medical or surgical conditions. HAIs are among the most common complications occurring during the health service delivery, often caused by endemic multidrug-resistant organisms on account of indiscriminate use of antibiotics.1 HAIs are associated with increased morbidity and mortality, prolonged hospital stays, and health-care costs. Surveillance for endemic HAIs is important to measure their burden, identify high-risk populations and procedures, and guide efforts to reduce HAI incidence. HAI surveillance is a core component of infection prevention and control programmes worldwide. The reliability of HAI surveillance depends on the use of standardised definitions. The case definitions used in National Healthcare Safety Network (NHSN) or European Centre for Disease Prevention and Control (ECDC) HAI surveillance are complex, requiring dedicated human resources and funds and expertise in diagnostics, epidemiology, and infection control. Probably on account of this, only 16% of low-income and middle-income countries (LMICs) in 2010 had HAI surveillance at the national and sub-national level.2
The frequency of different HAIs varies between countries and according to economic conditions. The risk of acquiring HAI is up to 20 times higher in LMICs.1 Surveillance from an International Nosocomial Infection Control Consortium comprising 45 LMICs, reported three to six times high pooled rates of catheter-associated urinary tract infection (CAUTI) and central line-associated bloodstream infections (CLABSI) compared with intensive care units (ICUs) in the USA.3 Surveillance data from 2004 to 2013 from 40 hospitals in India reported a pooled prevalence of CLABSI to be 5·1 per 1000 central line days and of CAUTI to be 2·1 per 1000 catheter days.4 A 2019, single-centre study in India reported a pooled CLABSI rate of 4·3 per 1000 central line days.5 In a global survey, the prevalence of resistance to antibiotics including third-generation cephalosporins and carbapenems among Enterobacteriaceae, was significantly higher in LMICs.6 High levels of resistance, including against carbapenems among Acinetobacter spp, Pseudomonas spp, and Klebsiella spp have been reported from India.7
In The Lancet Global Health, Purva Mathur and colleagues8 report results of health-care-associated bloodstream and urinary tract infections in 89 intensive care units of 26 tertiary care hospitals in India.8 The authors modified the NHSN and ECDC case definitions to facilitate standardised HAI surveillance, adjusting for the available resources in Indian hospitals. In adult and paediatric ICU types, the pooled rates of BSI ranged between 5·3–7·3 per 1000 patient days and CLABSI rates ranged between 8·3–12·1 per 1000 central line days. The pooled UTI and CAUTI rates in these ICUs ranged between 1·7–2·8 per 1000 patient days and 8·3–12·1 per 1000 catheter days, respectively. Neonatal ICUs had higher pooled BSI and CLABSI rates in all birthweight categories. The authors also report high levels of resistance to at least one carbapenem in HAIs caused by Klebsiella spp, Escherichia coli, Acinetobacter spp, and Pseudomonas spp. The rates of HAI and associated antibiotic resistance reported in this study are either similar to or higher than those from previous studies in India.
The HAI surveillance established by Mathur and colleagues8 represents a well laid foundation that needs to be continued and expanded further as a national-level surveillance system for major HAI, including ventilator-associated pneumonia and surgical site infection. However, the modified case definitions used in the study need to be validated before its large-scale implementation. This platform will also enable early detection and containment of outbreaks caused by novel or emerging infectious diseases and multidrug resistant organisms. The antimicrobial resistance data will inform local, regional, and national antimicrobial resistance stewardship strategies and initiatives. Linkage to other global HAI or antimicrobial resistance surveillance platforms, such as the Global Antimicrobial Resistance and Use Surveillance System, will enable learning and sharing of the best practices of infection prevention and control.
In India, a large segment of the population seeks in-patient health-care at secondary or district-level health facilities in public and private sectors, many of which have inadequate infection prevention and control measures. The major barriers to infection prevention and control implementation are scarcity of dedicated and trained staff, availability and inappropriate use of PPE, and sanitary and hygiene measures, compounded with patient overcrowding. The widespread transmission of infection in health facilities during the ongoing COVID-19 pandemic underscores the need for strengthening infection prevention and control practices.
In the past decade, there have been governmental initiatives, such as Kayakalp, aimed at improving and promoting the cleanliness, hygiene, waste management, and infection control practices in public health-care facilities in India.9 Although it is desirable that the national HAI surveillance system is eventually extended to district-level hospitals, the immediate priority should be to ensure that the minimum requirements of infection prevention and control are in place in these hospitals.10 The eventual outcomes of implementing evidence-based, best infection prevention and control practices will be a substantial reduction in HAIs and an improvement in the overall health-care quality.
We declare no competing interests.

Cost-effectiveness of gasless laparoscopy as a means to increase provision of minimally invasive surgery for abdominal conditions in rural North-East India

Laparoscopic surgery, a minimally invasive technique to treat abdominal conditions, has been shown to produce equivalent safety and efficacy with quicker return to normal function compared to open surgery. As such, it is widely accepted as a cost-effective alternative to open surgery for many abdominal conditions. However, access to laparoscopic surgery in rural North-East India is limited, in part due to limited equipment, unreliable supplies of CO2 gas, lack of surgical expertise and a shortage of anaesthetists. We evaluate the cost-effectiveness of gasless laparoscopy as a means to increase provision of minimally invasive surgery (MIS) for abdominal conditions in rural North-East India. A decision tree model was developed to compare costs, evaluated from a patient perspective, and health outcomes, disability adjusted life years (DALYs), associated with gasless laparoscopy, conventional laparoscopy or open abdominal surgery in rural North-East India. Results indicate that MIS (performed by conventional or gasless laparoscopy) is less costly and produces better outcomes, fewer DALYs, than open surgery. These results were consistent even when gasless laparoscopy was analysed using least favourable data from the literature. Scaling up provision of MIS through increased access to gasless laparoscopy would reduce the cost burden to patients and increase DALYs averted. Based on a sample of 12 facilities in the North-East region, if scale up was achieved so that all essential surgeries amenable to laparoscopic surgery were performed as such (using conventional or gasless laparoscopy), 64% of DALYS related to these surgeries could be averted, equating to an additional 454.8 DALYs averted in these facilities alone. The results indicate that gasless laparoscopy is likely to be a cost-effective alternative to open surgery for abdominal conditions in rural North-East India and provides a possible bridge to the adoption of full laparoscopic services.

Blindness and visual impairment and their causes in India: Results of a nationally representative survey

Introduction
Avoidable blindness is a significant public health problem in India. Nationally representative RAAB surveys (Rapid Assessment of Avoidable Blindness) are being conducted periodically in the country to know the current status of blindness in the country. The current study describes the findings from the RAAB survey conducted during 2015–19 in India.

Methodology
A cross-sectional, population-based survey was conducted across the entire country among persons aged 50 years and above using RAAB version 6 methodology. Presenting and pinhole visual acuity was recorded followed by lens examination using a torchlight. In order to estimate the prevalence of blindness and visual impairment in overall population in India, district weights were assigned to each of the 31 surveyed districts and the prevalence was standardized using the RAAB software.

Results
The overall weighted, age-gender standardized, prevalence of blindness (presenting visual acuity <3/60 in better eye) in population aged ≥50 years was 1.99% (95% CI 1.94%, 2.13%) and of visual impairment (VI) (presenting visual acuity <6/12 in better eye) was 26.68% (95% CI 26.57–27.17%). On multivariate analysis, adjusted odds ratio showed that blindness was associated with age ≥ 80 years (OR = 20.3, 95% CI: 15.6–26.4) and being illiterate (OR = 5.6, 95% CI: 3.6–8.9). Blindness was not found to be significantly associated with either gender or locality.

Conclusion
The results of the survey demonstrate that currently more than one fourth of persons aged 50 years and above are visually impaired (PVA<6/12 in better eye) in India. The prevalence of blindness among them is 1.99%, and older age and illiteracy are significantly associated with blindness. Major causes of blindness included cataract (66.2%), corneal opacity (CO) (8.2%), cataract surgical complications (7.2%), posterior segment disorders (5.9%) and glaucoma (5.5%). The proportion of blindness and visual impairment that is due to avoidable causes include 92.9% and 97.4% respectively.

A cohort study of differences in trauma outcomes between females and males at four Indian Urban Trauma Centers

Background Studies from high income countries suggest improved survival for females as compared to males following trauma. However, data regarding differences in trauma outcomes between females and males is severely lacking from low- and middle-income countries. The objective of this study was to determine the association between sex and clinical outcomes amongst Indian trauma patients using the Australia-India Trauma Systems Collaboration database.
Methods A prospective multicentre cohort study was performed across four urban public hospitals in India April 2016 through February 2018. Bivariate analyses compared admission physiological parameters and mechanism of injury. Logistic regression assessed association of sex with the primary outcomes of 30-day and 24-hour in-hospital mortality. Secondary outcomes included ICU admission, ICU length of stay, ventilator requirement, and time on a ventilator.
Results Of 8,605 patients, 1,574 (18.3%) were females. The most common mechanism of injury was falls for females (52.0%) and road traffic injury for males (49.5%). On unadjusted analysis, there was no difference in 30-day in-hospital mortality between females (11.6%) and males (12.6%, p = 0.323). However, females demonstrated a lower mortality at 24-hours (1.1% vs males 2.1%, p = 0.011) on unadjusted analysis. Females were also less likely to require a ventilator (17.3% vs 21.0% males, p = 0.001) or ICU admission (34.4% vs 37.5%, p = 0.028). Stratification by age or by ISS demonstrated no difference in 30-day in-hospital mortality for males vs females across age and ISS categories. On multivariable regression analysis, sex was not associated significantly with 30-day or 24-hour in-hospital mortality.
Conclusion This study did not demonstrate a significant difference in the 30-day trauma mortality or 24-hour trauma mortality between female and male trauma patients in India on adjusted analyses. A more granular data is needed to understand the interplay of injury severity, immediate post-traumatic hormonal and immunological alterations, and the impact of gender-based disparities in acute care settings.

Early treatment of corneal abrasions and ulcers–estimating clinical and economic outcomes

Background
In low-and-middle income countries, corneal abrasions and ulcers are common and not always well managed. Previous studies showed better clinical outcomes with early presentation and treatment of minor abrasions, however, there have been no formal studies estimating the financial impact of early treatment of abrasions and ulcers compared to delayed treatment.

Methods
We used the LV Prasad Eye Institute’s (LVPEI’s) electronic health record system (eyeSmart) to estimate the impact of early presentation on clinical outcomes associated with abrasions and ulcers. 861 patients with corneal abrasion and 1821 patients with corneal ulcers were studied retrospectively, and 134 patients with corneal abrasion prospectively. A health economic model was constructed based on LVPEI cost data for a range of patient scenarios (from early presentation with abrasion to late presentation with ulcer).

Findings
Our findings suggest that delayed presentation of corneal abrasion results in poor clinical and economic outcomes due to increased risk of ulceration requiring more extensive surgical management, increasing associated costs to patients and the healthcare system. However, excellent results at low cost can be achieved by treatment of patients with early presentation of abrasions at village level health care centres.

Interpretation
Treatment of early minor corneal abrasions, particularly using local delivery of treatment, is effective clinically and economically. Future investment in making patients aware of the need to react promptly to corneal abrasions by accessing local healthcare resources (coupled with a campaign to prevent ulcerations occurring) will continue to improve clinical outcomes for patients at low cost and avoid complex and more expensive treatment to preserve sight.

Funding
This research was funded by the Medical Research Council, grant MR/S004688/1.

A study of clinical and economic burden of surgical site infection in patients undergoing caesarian section at a tertiary care teaching hospital in India

Background
Caesarian section is one of the most commonly performed surgeries in India. Determination of the incidence as well as the clinical and financial burden of post caesarian surgical site infection (SSI) is of critical importance for all the stakeholders for rational and fair allocation of resources.

Methods
This study was a prospective observational case-control study. The mean direct and indirect cost of treatment for the cases were compared with the control patients. An unpaired t-test was used to compare the mean between the two groups.

Results
Out of 2024 patients, who underwent caesarian section during the study period, 114 had acquired incisional surgical site infection (ISSI), with the infection incidence being 5.63%. The total cost of illness due to post caesarian ISSI was almost three times higher compared to the non-infected matched control group. (P<0.0001). An average length of hospital stay in the ISSI patient group was 10 days longer than that in the control group (P<0.0001) and importantly total length of antimicrobial therapy(LOT) in patients with ISSI was also almost three times higher than the control group (P<0.0001).

Conclusion
The development of post caesarian SSI imposes a significant clinical as well as a financial burden. The study highlights the necessity of taking effective preventive measures to decrease the incidence of SSI.

How much do government and households spend on an episode of hospitalisation in India? A comparison for public and private hospitals in Chhattisgarh state

Background
Improvements in the financing of healthcare services are important for developing countries like India to make progress towards universal health coverage. Inpatient-care contributes to a big share of total health expenditure in India. India has a mixed health-system with a sizeable presence of private hospitals. Existing studies show that out-of-pocket expenditure (OOPE) incurred per hospitalisation in private hospitals was greater than public facilities. But, such comparisons have not taken into account the healthcare spending by government.

Methods
For a valid comparison between public and for-profit private providers, this study in Indian state of Chhattisgarh assessed the combined spending by government and households per episode of hospitalisation. The supply-side and demand-side spending from public and private sources was taken into account. The study used two datasets: a) household survey for data on hospital utilisation, OOPE, cash incentives received by patients and claims raised under publicly funded health insurance (PFHI) schemes (n = 903 hospitalisation episodes) b) survey of public facilities to find supply-side government spending per hospitalisation (n = 64 facilities).

Results
Taking into account all relevant demand and supply side expenditures, the average total spending per day of hospitalisation was INR 2833 for public hospitals and INR 6788 for private hospitals. Adjusted model for logarithmic transformation of OOPE while controlling for variables including case-mix showed that a hospitalisation in private hospitals was significantly more expensive than public hospitals (coefficient = 2.9, p < 0.001). Hospitalisations in private hospitals were more likely to result in a PFHI claim (adjusted-odds-ratio = 1.45, p = 0.02) and involve a greater amount than public hospitals (coefficient = 0.27, p < 0.001). Propensity-score matching models confirmed the above results.

Overall, supply-side public spending contributed to 16% of total spending, demand-side spending through PFHI to 16%, cash incentives to 1% and OOPE to 67%. OOPE constituted 31% of total spending per episode in public and 86% in private hospitals.

Conclusions
Government and households put together spent substantially more per hospitalisation in private hospitals than public hospitals in Chhattisgarh. This has important implications for the allocative efficiency and the desired public-private provider-mix. Using public resources for purchasing inpatient care services from private providers may not be a suitable strategy for such contexts.

Implementing the WHO Labour Care Guide to reduce the use of Caesarean section in four hospitals in India: protocol and statistical analysis plan for a pragmatic, stepped-wedge, cluster-randomized pilot trial

BACKGROUND
The World Health Organization (WHO) Labour Care Guide (LCG) is a paper-based labour monitoring tool designed to facilitate the implementation of WHO’s latest guidelines for effective, respectful care during labour and childbirth. Implementing the LCG into routine intrapartum care requires a strategy that improves healthcare provider practices during labour and childbirth. Such a strategy might optimize the use of Caesarean section (CS), along with potential benefits on the use of other obstetric interventions, maternal and perinatal health outcomes, and women’s experience of care. However, the effects of a strategy to implement the LCG have not been evaluated in a randomised trial. This study aims to: 1) develop and optimise a strategy for implementing the LCG (formative phase); and 2) To evaluate the implementation of the LCG strategy compared with usual care (trial phase).

METHODS
In the formative phase, we will co-design the LCG strategy with key stakeholders informed by facility assessments and provider surveys, which will be field tested in one hospital. The LCG strategy includes a LCG training program, ongoing supportive supervision from senior clinical staff, and audit and feedback using the Robson Classification. We will then conduct a stepped-wedge, cluster-randomized pilot trial in four public hospitals in India, to evaluate the effect of the LCG strategy intervention compared to usual care (simplified WHO partograph). The primary outcome is the CS rate in nulliparous women with singleton, term, cephalic pregnancies in spontaneous labour (Robson Group 1). Secondary outcomes include clinical and process of care outcomes, as well as women’s experience of care outcomes. We will also conduct a process evaluation during the trial, using standardized facility assessments, in-depth interviews and surveys with providers, audits of completed LCGs, labour ward observations and document reviews. An economic evaluation will consider implementation costs and cost-effectiveness.

DISCUSSION
Findings of this trial will guide clinicians, administrators and policymakers on how to effectively implement the LCG, and what (if any) effects the LCG strategy has on process of care, health and experience outcomes. The trial findings will inform the rollout of LCG internationally.

TRIAL REGISTRATION:
CTRI/2021/01/030695 (Protocol version 1.4, 25 April 2022)