Measurement of health system performance at district level: A study protocol

Background: Limited efforts have been observed in low and middle income countries to undertake health system performance assessment at district level. Absence of a comprehensive data collection tool and lack of a standardised single summary measure defining overall performance are some of the main problems. Present study has been undertaken to develop a summary composite health system performance index at district level. Methods: A broad range of indicators covering all six domains as per building block framework were finalized by an expert panel. The domains were classified into twenty sub-domains, with 70 input and process indicators to measure performance. Seven sub-domains for assessing health system outputs and outcomes were identified, with a total of 28 indicators. Districts in Haryana state from north India were selected for the study. Primary and secondary data will be collected from 378 health facilities, district and state health directorate headquarters. Indicators will be normalized, aggregated to generate composite performance index at district level. Domain specific scores will present the quality of individual building block domains in the public health system. Robustness of the results will be checked using sensitivity analysis. Expected impact for public health: The study presents a methodology for comprehensive assessment of all health system domains on basis of input, process, output and outcome indicators which has never been reported from India. Generation of this index will help identify policy and implementation areas of concern and point towards potential solutions. Results may also help understand relationships between individual building blocks and their sub-components

Cost-effectiveness of therapeutic use of safety-engineered syringes in healthcare facilities in India

Background: Globally, 16 billion injections are administered each year of which 95% are for curative care. India contributes 25–30% of the global injection load. Over 63% of these injections are reportedly unsafe or deemed unnecessary. Objectives: To assess the incremental cost per quality-adjusted life-year (QALY) gained with the introduction of safety-engineered syringes (SES) as compared to disposable syringes for therapeutic care in India. Methods: A decision tree was used to compute the volume of needle-stick injuries (NSIs) and reuse episodes among healthcare professionals and the patient population. Subsequently, three separate Markov models were used to compute lifetime costs and QALYs for individuals infected with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Three SES were evaluated—reuse prevention syringe (RUP), sharp injury prevention (SIP) syringe, and syringes with features of both RUP and SIP. A lifetime study horizon starting from a base year of 2017 was considered appropriate to cover all costs and consequences comprehensively. A systematic review was undertaken to assess the SES effects in terms of reduction in NSIs and reuse episodes. These were then modelled in terms of reduction in transmission of blood-borne infections, life-years and QALYs gained. Future costs and consequences were discounted at the rate of 3%. Incremental cost per QALY gained was computed to assess the cost-effectiveness. A probabilistic sensitivity analysis was undertaken to account for parameter uncertainties. Results: The introduction of RUP, SIP and RUP + SIP syringes in India is estimated to incur an incremental cost of Indian National Rupee (INR) 61,028 (US$939), INR 7,768,215 (US$119,511) and INR 196,135 (US$3017) per QALY gained, respectively. A total of 96,296 HBV, 44,082 HCV and 5632 HIV deaths are estimated to be averted due to RUP in 20 years. RUP has an 84% probability to be cost-effective at a threshold of per capita gross domestic product (GDP). The RUP syringe can become cost saving at a unit price of INR 1.9. Similarly, SIP and RUP + SIP syringes can be cost-effective at a unit price of less than INR 1.2 and INR 5.9, respectively. Conclusion: RUP syringes are estimated to be cost-effective in the Indian context. SIP and RUP + SIP syringes are not cost-effective at the current unit prices. Efforts should be made to bring down the price of SES to improve its cost-effectiveness

Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial

Background Evidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation. Methods In this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India. Eligible infants were tracked from birth and randomly assigned (1:1) at 4 months corrected age to receive complementary feeding at 4 months corrected age (4 month group), or continuation of milk feeding and initiation of complementary feeding at 6 months corrected age (6 month group), using computer generated randomisation schedule of variable block size, stratified by gestation (30 weeks or less, and 31–33 weeks). Iron supplementation was provided as standard. Participants and the implementation team could not be masked to group assignment, but outcome assessors were masked. Primary outcome was weight for age Z-score at 12 months corrected age (WAZ12) based on WHO Multicentre Growth Reference Study growth standards. Analyses were by intention to treat. The trial is registered with Clinical Trials Registry of India, number CTRI/2012/11/003149. Findings Between March 20, 2013, and April 24, 2015, 403 infants were randomly assigned: 206 to receive complementary feeding from 4 months and 197 to receive complementary feeding from 6 months. 22 infants in the 4 month group (four deaths, two withdrawals, 16 lost to follow-up) and eight infants in the 6 month group (two deaths, six lost to follow-up) were excluded from analysis of primary outcome. There was no difference in WAZ12 between two groups: –1·6 (SD 1·2) in the 4 month group versus –1·6 (SD 1·3) in the 6 month group (mean difference 0·005, 95% CI –0·24 to 0·25; p=0·965). There were more hospital admissions in the 4 month group compared with the 6 month group: 2·5 episodes per 100 infant-months in the 4 month group versus 1·4 episodes per 100 infant-months in the 6 month group (incidence rate ratio 1·8, 95% CI 1·0–3·1, p=0·03). 34 (18%) of 188 infants in the 4 month group required hospital admission, compared with 18 (9%) of 192 infants in the 6 month group. Interpretation Although there was no evidence of effect for the primary endpoint of WAZ12, the higher rate of hospital admission in the 4 month group suggests a recommendation to initiate complementary feeding at 6 months over 4 months of corrected age in infants less than 34 weeks of gestation

Towards climate-smart agricultural policies and investments in Telangana

This briefing note summarizes the key findings of the “Scaling up climate-smart agriculture in the Telangana State” project, carried out by the International Crops Research Institute for the Semi-Arid Tropics and partners, between 1st January 2016 and 31st December 2017

Tumor reversion: a dream or a reality.

Reversion of tumor to a normal differentiated cell once considered a dream is now at the brink of becoming a reality. Different layers of molecules/events such as microRNAs, transcription factors, alternative RNA splicing, post-transcriptional, post-translational modifications, availability of proteomics, genomics editing tools, and chemical biology approaches gave hope to manipulation of cancer cells reversion to a normal cell phenotype as evidences are subtle but definitive. Regardless of the advancement, there is a long way to go, as customized techniques are required to be fine-tuned with precision to attain more insights into tumor reversion. Tumor regression models using available genome-editing methods, followed by in vitro and in vivo proteomics profiling techniques show early evidence. This review summarizes tumor reversion developments, present issues, and unaddressed challenges that remained in the uncharted territory to modulate cellular machinery for tumor reversion towards therapeutic purposes successfully. Ongoing research reaffirms the potential promises of understanding the mechanism of tumor reversion and required refinement that is warranted in vitro and in vivo models of tumor reversion, and the potential translation of these into cancer therapy. Furthermore, therapeutic compounds were reported to induce phenotypic changes in cancer cells into normal cells, which will contribute in understanding the mechanism of tumor reversion. Altogether, the efforts collectively suggest that tumor reversion will likely reveal a new wave of therapeutic discoveries that will significantly impact clinical practice in cancer therapy

Type 1 diabetes, COVID-19 vaccines and short-term safety: Subgroup analysis from the global COVAD study

AIMS/INTRODUCTION Coronavirus disease 2019 (COVID-19) vaccinations have been proven to be generally safe in healthy populations. However, the data on vaccine safety in patients with type 1 diabetes are scarce. This study aimed to evaluate the frequency and severity of short-term (<7-day) adverse vaccination events (AEs) and their risk factors among type 1 diabetes patients. MATERIALS AND METHODS This study analyzed data from the COVID-19 vaccination in Autoimmune Diseases (COVAD) survey database (May to December 2021; 110 collaborators, 94 countries), comparing <7-day COVID-19 vaccine AE among type 1 diabetes patients and healthy controls (HCs). Descriptive statistics; propensity score matching (1:4) using the variables age, sex and ethnicity; and multivariate analyses were carried out. RESULTS This study analyzed 5,480 completed survey responses. Of all responses, 5,408 were HCs, 72 were type 1 diabetes patients (43 females, 48.0% white European ancestry) and Pfizer was the most administered vaccine (39%). A total of 4,052 (73.9%) respondents had received two vaccine doses. Patients with type 1 diabetes had a comparable risk of injection site pain, minor and major vaccine AEs, as well as associated hospitalizations to HCs. However, type 1 diabetes patients had a higher risk of severe rashes (3% vs 0.4%, OR 8.0, 95% confidence interval 1.7-36), P = 0.007), although reassuringly, these were rare (n = 2 among type 1 diabetes patients). CONCLUSIONS COVID-19 vaccination was safe and well tolerated in patients with type 1 diabetes with similar AE profiles compared with HCs, although severe rashes were more common in type 1 diabetes patients

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Vaccine Platforms Combining Circumsporozoite Protein and Potent Immune Modulators, rEA or EAT-2, Paradoxically Result in Opposing Immune Responses

Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS) protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd) based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI) responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA) or SLAM receptors adaptor protein (EAT-2). Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly improve the induction of malaria antigen specific adaptive immune responses in vivo

Sensitivity of the Advanced LIGO detectors at the beginning of gravitational wave astronomy

The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10−23/Hz−−−√ was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30  M⊙ could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914