Quantifying viscosity and elasticity using holographic imaging by Rayleigh wave dispersion.

Viscoelasticity is an important diagnostic parameter to investigate physiological dysfunctions in biological tissues. This Letter reports the quantification of viscoelastic parameters by Rayleigh wave tracing on the surface of tissue-mimicking phantoms using holographic imaging. The Rayleigh wave is induced by an electromechanical actuator on the surface of oil-in-gelatin phantoms and a biological tissue sample followed by holographic imaging and reconstruction of the wave. The frequency-dependent velocity dispersion is fitted to a Voigt model for the quantification of viscous and elastic moduli. The viscoelastic parameters calculated by the proposed method are validated by comparing the results from a conventional mechanical rheometer.

Gender, health and ageing in Fiji: a mixed methods analysis.

BACKGROUND: Women are disadvantaged by ageing: older women are more likely than older men to suffer from ill-health, have less access to health care and suffer discrimination within the health care system. Globally, there is a dearth of health research on gender and ageing with substantial knowledge gaps in low and middle-income country contexts. Part of a wider investigation on health and ageing in Fiji, our objective was to identify and describe gendered differences in healthy ageing in this Pacific Island context. We believe this to be the first such study in the Pacific region. METHODS: Applying a health systems lens, we used a mixed-methods approach, encompassing analysis of cause of death data; focus group discussion to gather community and family attitudes to health services; and policy analysis, and then used data triangulation techniques to draw out key themes and insights. RESULTS: We found that gender affects health outcomes among older persons, attitudes towards and experience of healthy ageing, and an older person's access to and use of health services. We also found that while Fiji's policy response to ageing has recognised the importance of gender, to-date there has been limited action to address gender differences. Gender (as oppose to sex differences) has direct and indirect implications for the health of older Fijians, while gendered inequalities and patriarchal norms appear to affect both men and women's experience of ageing and the health system response. Further, gender and age discrimination may be intersecting, intensifying their separate effects. CONCLUSION: This study demonstrates the feasibility and importance of applying a gender lens to the study of healthy ageing. Our findings from Fiji may be relevant to other island nations in the south Pacific which share similar challenges of population ageing, a constrained health budget and geographically-dispersed populations. The data triangulation methodology may be considered an efficient and insightful way to examine gendered responses to healthy ageing elsewhere.

Optofluidic bioimaging platform for quantitative phase imaging of lab on a chip devices using digital holographic microscopy.

We propose a versatile 3D phase-imaging microscope platform for real-time imaging of optomicrofluidic devices based on the principle of digital holographic microscopy (DHM). Lab-on-chip microfluidic devices fabricated on transparent polydimethylsiloxane (PDMS) and glass substrates have attained wide popularity in biological sensing applications. However, monitoring, visualization, and characterization of microfluidic devices, microfluidic flows, and the biochemical kinetics happening in these devices is difficult due to the lack of proper techniques for real-time imaging and analysis. The traditional bright-field microscopic techniques fail in imaging applications, as the microfluidic channels and the fluids carrying biological samples are transparent and not visible in bright light. Phase-based microscopy techniques that can image the phase of the microfluidic channel and changes in refractive indices due to the fluids and biological samples present in the channel are ideal for imaging the fluid flow dynamics in a microfluidic channel at high resolutions. This paper demonstrates three-dimensional imaging of a microfluidic device with nanometric depth precisions and high SNR. We demonstrate imaging of microelectrodes of nanometric thickness patterned on glass substrate and the microfluidic channel. Three-dimensional imaging of a transparent PDMS optomicrofluidic channel, fluid flow, and live yeast cell flow in this channel has been demonstrated using DHM. We also quantify the average velocity of fluid flow through the channel. In comparison to any conventional bright-field microscope, the 3D depth information in the images illustrated in this work carry much information about the biological system under observation. The results demonstrated in this paper prove the high potential of DHM in imaging optofluidic devices; detection of pathogens, cells, and bioanalytes on lab-on-chip devices; and in studying microfluidic dynamics in real time based on phase changes.

Lipid-lipid interactions in aminated reduced graphene oxide interface for biosensing application.

A label-free biosensor based on antiapolipoprotein B 100 functionalized-aminated reduced graphene oxide interface has been fabricated for detection of low density lipoprotein (LDL or lipid) cholesterol. The aminated reduced graphene oxide (NH2-rGO) based electrode surface is covalently functionalized with antiapolipoprotein B 100 (AAB or lipid) using EDC/NHS coupling chemistry. The lipid-lipid interactions at the NH2-rGO electrode surface have been investigated using electrochemical impedance spectroscopic technique. The structural and morphological investigations of NH2-rGO based immunosensor have been accomplished via transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, UV-visible, and electrochemical techniques. The impedimetric response of the proposed immunosensor shows excellent sensitivity (612 Ω mg(-1) dL cm(-2)), a response time of 250 s, and a low detection limit of 5 mg/dL of LDL molecules. The association, dissociation, and equilibrium rate constants for this immunoelectrode are found to be 1.66 M(-1) s(-1), 0.6 s(-1), and 2.77 M(-1), respectively. The long-term stability and excellent reproducibility of the proposed immunosensor indicates a suitable platform for detection of LDL or lipid molecules. This immunosensor provides an efficient platform for analysis of the antigen-antibody interactions of lipid molecules.

High-resolution lensless holographic microscopy using a physics-aware deep network.

Significance: Lensless digital inline holographic microscopy (LDIHM) is an emerging quantitative phase imaging modality that uses advanced computational methods for phase retrieval from the interference pattern. The existing end-to-end deep networks require a large training dataset with sufficient diversity to achieve high-fidelity hologram reconstruction. To mitigate this data requirement problem, physics-aware deep networks integrate the physics of holography in the loss function to reconstruct complex objects without needing prior training. However, the data fidelity term measures the data consistency with a single low-resolution hologram without any external regularization, which results in a low performance on complex biological data. Aim: We aim to mitigate the challenges with trained and physics-aware untrained deep networks separately and combine the benefits of both methods for high-resolution phase recovery from a single low-resolution hologram in LDIHM. Approach: We propose a hybrid deep framework (HDPhysNet) using a plug-and-play method that blends the benefits of trained and untrained deep models for phase recovery in LDIHM. The high-resolution phase is generated by a pre-trained high-definition generative adversarial network (HDGAN) from a single low-resolution hologram. The generated phase is then plugged into the loss function of a physics-aware untrained deep network to regulate the complex object reconstruction process. Results: Simulation results show that the SSIM of the proposed method is increased by 0.07 over the trained and 0.04 over the untrained deep networks. The average phase-SNR is elevated by 8.2 dB over trained deep models and 9.8 dB over untrained deep networks on the experimental biological cells (cervical cells and red blood cells). Conclusions: We showed improved performance of the HDPhysNet against the unknown perturbation in the imaging parameters such as the propagation distance, the wavelength of the illuminating source, and the imaging sample compared with the trained network (HDGAN). LDIHM, combined with HDPhysNet, is a portable and technology-driven microscopy best suited for point-of-care cytology applications.

TIE-GANs: single-shot quantitative phase imaging using transport of intensity equation with integration of GANs.

Significance: Artificial intelligence (AI) has become a prominent technology in computational imaging over the past decade. The expeditious and label-free characteristics of quantitative phase imaging (QPI) render it a promising contender for AI investigation. Though interferometric methodologies exhibit potential efficacy, their implementation involves complex experimental platforms and computationally intensive reconstruction procedures. Hence, non-interferometric methods, such as transport of intensity equation (TIE), are preferred over interferometric methods. Aim: TIE method, despite its effectiveness, is tedious as it requires the acquisition of many images at varying defocus planes. The proposed methodology holds the ability to generate a phase image utilizing a single intensity image using generative adversarial networks (GANs). We present a method called TIE-GANs to overcome the multi-shot scheme of conventional TIE. Approach: The present investigation employs the TIE as a QPI methodology, which necessitates reduced experimental and computational efforts. TIE is being used for the dataset preparation as well. The proposed method captures images from different defocus planes for training. Our approach uses an image-to-image translation technique to produce phase maps and is based on GANs. The main contribution of this work is the introduction of GANs with TIE (TIE:GANs) that can give better phase reconstruction results with shorter computation times. This is the first time the GANs is proposed for TIE phase retrieval. Results: The characterization of the system was carried out with microbeads of 4 µm size and structural similarity index (SSIM) for microbeads was found to be 0.98. We demonstrated the application of the proposed method with oral cells, which yielded a maximum SSIM value of 0.95. The key characteristics include mean squared error and peak-signal-to-noise ratio values of 140 and 26.42 dB for oral cells and 100 and 28.10 dB for microbeads. Conclusions: The proposed methodology holds the ability to generate a phase image utilizing a single intensity image. Our method is feasible for digital cytology because of its reported high value of SSIM. Our approach can handle defocused images in such a way that it can take intensity image from any defocus plane within the provided range and able to generate phase map.

CKD is the Major Cause of Death in Uddanam: A Population-Representative Study Using Smart Verbal Autopsy.

Introduction: Uddanam is an agricultural area with a high burden of chronic kidney disease of unknown etiology (CKDu). Despite reports of many deaths due to CKD in the lay press, the exact contribution of CKD to deaths remains uncertain because most deaths occur outside medical care. Methods: We used SmartVA automated verbal autopsy tool to ascertain the cause-specific mortality fractions among a 2419 subject-strong general population cohort of adult subjects in Uddanam between 2018 and 2022. Verbal autopsy interviews were conducted twice with the family members of the deceased. Results: A total of 133 deaths were recorded, giving a crude death rate of 5.5%, 10 times higher than that recorded in national surveys. CKD was responsible for 45% of all deaths, followed by ischemic heart disease (15%) and respiratory disease (6%). Conclusion: This study confirms CKD as the leading cause of mortality in this high CKD burden area and provides crucial data for public health decision-making and resource allocation.

Electrochemical and Plasmonic Detection of Myocardial Infarction Using Microfluidic Biochip Incorporated with Mesoporous Nanoscaffolds.

This paper reports a microfluidic device for the electrochemical and plasmonic detection of cardiac myoglobin (cMb) and cardiac troponin I (cTnI) with noticeable limits of detection (LoD) as low as a few picograms per milliliter (pg/mL) ranges, achieved in a short detection time. The device features two working electrodes, each with a mesoporous Ni3V2O8 nanoscaffold grafted with reduced graphene oxide (rGO) that improves the interaction of diffusing analyte molecules with the sensing surface by providing a high surface area and reaction kinetics. Electrochemical studies reveal sensitivities as high as 9.68 µA ng/mL and a LoD of 2.0 pg/mL for cTnI, and 8.98 µA ng/mL and 4.7 pg/mL for cMb. Additionally, the surface plasmon resonance (SPR) studies demonstrate a low-level LoD of 8.8 pg/mL for cMb and 7.3 pg/mL for cTnI. The dual-modality sensor enables dynamic tracking of kinetic antigen-antibody interactions during sensing, self-verification through providing signals of two modes, and reduced false readout. This study demonstrates the complementary nature of the electrochemical and SPR modes in biosensing, with the electrochemical mode being highly sensitive and the SPR mode providing superior tracking of molecular recognition behaviors. The presented sensor represents a significant innovation in cardiovascular disease management and can be applied to monitor other clinically important biomolecules.

Global lessons on delivery of primary healthcare services for people with non-communicable diseases: convergent mixed methods.

OBJECTIVE: To extract key lessons on primary healthcare (PHC) service delivery strategies for non-communicable diseases (NCD) from the work of researchers funded by the Global Alliance for Chronic Diseases (GACD). DESIGN: A convergent mixed methods study that extracted data using a standardised template from research projects funded by the GACD that focused on PHC. The strategies implemented in these studies were mapped onto the PHC Performance Initiative framework. Semistructured qualitative interviews were conducted with researchers from purposefully selected projects to understand the strategies and contextual factors in more depth. SETTING: PHC contexts from low or middle-income countries (LMIC) as well as vulnerable groups within high-income countries. Projects came from all regions of the world, particularly East Asia and Pacific, sub-Saharan Africa, South Asia, Latin America and Caribbean. PARTICIPANTS: The study extracted data on 84 research projects and interviewed researchers from 16 research projects. RESULTS: Research projects came from all regions of the world, and mainly focused on diabetes (35.3%), hypertension (28.3%) and mental health (27.6%). Mapped onto the PHC Performance Initiative framework: 49.4% focused on high-quality PHC (particularly the comprehensiveness of NCD care, 41.2%); 41.2% on the availability of PHC services (particularly the competence of healthcare workers, 36.5%); 35.3% on population health management (particularly community-based services, 35.3%); 34.1% on facility organisation and management (particularly team-based care, 20.0%) and 31.8% on access (particularly digital technology, 23.5%). Most common strategies were task shifting and training to improve the comprehensiveness of NCD care through community-based services. Contextual factors related to inputs: infrastructure, equipment and medication, workforce (particularly community health workers), finances, health information systems and digital technology. CONCLUSION: Key strategies and contextual factors to improve PHC service delivery for NCDs in LMICs were identified. These strategies should combine with other strategies to strengthen the PHC system as a whole, while improving care for NCDs.

Rationale, Design, and Intervention Development of a Mobile Health-Led Primary Care Program for Management of Type 2 Diabetes in Rural Thailand: Protocol for a SMARThealth Diabetes Study.

BACKGROUND: Noncommunicable diseases (NCDs), particularly diabetes and chronic kidney diseases, pose a significant health burden in Thailand, especially among socioeconomically disadvantaged populations. The existing primary health care system faces challenges in providing optimal care for NCDs due to inadequate primary care workforce. The SMARThealth program offers a technology-based solution to enhance NCD management through task-sharing among nonphysician health care workers. OBJECTIVE: This study aims to adapt and implement the SMARThealth Diabetes program in rural Thailand to improve diabetes management. The main objectives are to (1) adapt, validate, and integrate the SMARThealth Diabetes program for improving the management of type 2 diabetes mellitus at the primary health care level; and (2) to determine the feasibility and acceptability of the SMARThealth Diabetes program in rural communities of Thailand. METHODS: A pragmatic, type 2 hybrid effectiveness or implementation, parallel-group cluster randomized controlled trial of 12 months duration and involving 51 subdistrict health offices in rural communities of Kamphaeng Phet province, Thailand, will be conducted. The intervention arm will receive the SMARThealth Diabetes program, including workforce restructuring, clinical decision support system, and continuous performance monitoring, while the control arm will continue with usual practice. Data will be collected using the SMARThealth platform and will be stored on a server in Thailand. The primary outcome measure will be the change in mean hemoglobin A1c (HbA1c) measured at randomization and 12 months from randomization between the intervention and control clusters. Secondary outcomes will include the difference in change in albuminuria status, estimated glomerular filtration rate, systolic blood pressure, and low-density lipoprotein cholesterol level. The analysis for change in HbA1c between baseline and end of study will be performed using linear mixed models. Any imbalances between the 2 arms will be addressed by sensitivity analyses. Additionally, a mixed methods process evaluation will be conducted to assess the implementation process, that will include in-depth interviews and focus group discussions, in addition to the quantitative data collected during the implementation process. The qualitative data will be thematically analyzed to explore factors that promote or inhibit the implementation and maintenance of the program. RESULTS: The data collection commenced in November 2022, and the results will be ready for publication by the first quarter of 2025. Effectiveness of the intervention package will be assessed by change in mean HbA1c measures, and detailed feasibility, barriers, and enablers for the implementation of the intervention will be documented through a detailed process evaluation. CONCLUSIONS: The study protocol outlines a novel approach to enhancing diabetes management in rural Thailand through digital technology-based interventions that will facilitate task-sharing among health care workers. This can help inform future strategies for improving NCD care in low-resource settings globally. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20200322006; https://www.thaiclinicaltrials.org/show/TCTR20200322006. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59266.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

OBJECTIVES: To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. METHODS: This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. RESULTS: We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. CONCLUSIONS: Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

Development of a risk prediction model for postpartum onset of type 2 diabetes mellitus, following gestational diabetes; the lifestyle InterVention in gestational diabetes (LIVING) study.

AIMS: This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth. METHODS: Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators. RESULTS: Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively. CONCLUSIONS: These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application.

Three-dimensional optical coherence tomography for optical biopsy of lymph nodes and assessment of metastatic disease.

BACKGROUND: Numerous techniques have been developed for localizing lymph nodes before surgical resection and for their histological assessment. Nondestructive high-resolution transcapsule optical imaging of lymph nodes offers the potential for in situ assessment of metastatic involvement, potentially during surgical procedures. METHODS: Three-dimensional optical coherence tomography (3-D OCT) was used for imaging and assessing resected popliteal lymph nodes from a preclinical rat metastatic tumor model over a 9-day time-course study after tumor induction. The spectral-domain OCT system utilized a center wavelength of 800 nm, provided axial and transverse resolutions of 3 and 12 µm, respectively, and performed imaging at 10,000 axial scans per second. RESULTS: OCT is capable of providing high-resolution label-free images of intact lymph node microstructure based on intrinsic optical scattering properties with penetration depths of ~1-2 mm. The results demonstrate that OCT is capable of differentiating normal, reactive, and metastatic lymph nodes based on microstructural changes. The optical scattering and structural changes revealed by OCT from day 3 to day 9 after the injection of tumor cells into the lymphatic system correlate with inflammatory and immunological changes observed in the capsule, precortical regions, follicles, and germination centers found during histopathology. CONCLUSIONS: We report for the first time a longitudinal study of 3-D transcapsule OCT imaging of intact lymph nodes demonstrating microstructural changes during metastatic infiltration. These results demonstrate the potential of OCT as a technique for intraoperative, real-time in situ 3-D optical biopsy of lymph nodes for the intraoperative staging of cancer.

In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes.

Dynamic magnetomotion of magnetic nanoparticles (MNPs) detected with magnetomotive optical coherence tomography (MM-OCT) represents a new methodology for contrast enhancement and therapeutic interventions in molecular imaging. In this study, we demonstrate in vivo imaging of dynamic functionalized iron oxide MNPs using MM-OCT in a preclinical mammary tumor model. Using targeted MNPs, in vivo MM-OCT images exhibit strong magnetomotive signals in mammary tumor, and no significant signals were measured from tumors of rats injected with nontargeted MNPs or saline. The results of in vivo MM-OCT are validated by MRI, ex vivo MM-OCT, Prussian blue staining of histological sections, and immunohistochemical analysis of excised tumors and internal organs. The MNPs are antibody functionalized to target the human epidermal growth factor receptor 2 (HER2 neu) protein. Fc-directed conjugation of the antibody to the MNPs aids in reducing uptake by macrophages in the reticulo-endothelial system, thereby increasing the circulation time in the blood. These engineered magnetic nanoprobes have multifunctional capabilities enabling them to be used as dynamic contrast agents in MM-OCT and MRI.

The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study.

AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).

Surface wave elastography using high speed full-field optical interferometry.

The assessment of mechanical stiffness is an essential diagnostic tool for investigating the biomechanical properties of biological tissues. Surface wave elastography (SWE) is an emerging technique to quantify elastic properties of tissues in clinical diagnosis. High-speed optical imaging combined with SWE has enormous potential in quantifying the elastic properties of tissues at microscale resolutions. In this study, we implement surface wave elastography using high-speed optical interferometry to characterize the elastic properties of tissue-mimicking phantoms andex-vivonative caprine liver tissue by imaging the surface wave induced by an electromechanical actuator. The sinusoidal mechanical excitations ranging from 120 Hz to 1.2 kHz on the surface of tissues are captured using a high-speed camera with a frame rate of 4 kHz at micrometer resolutions. The surface wavefront reconstruction is performed using a phase-shifting algorithm and linear regression is used to calculate the surface wave velocity. The mechanical stiffness estimated from the optical system is compared with the results of mechanical compression testing measurements. The results from this multimodal platform combining optical interferometry and vibrational spectroscopy using SWE are highly promising towards a non-invasive or minimally invasive imaging forin-vivoandex-vivomechanical characterization of tissues with future clinical applications.

Cost-Effectiveness of Population Screening Programs for Cardiovascular Diseases and Diabetes in Low- and Middle-Income Countries: A Systematic Review.

Almost all low- and middle-income countries (LMICs) have instated a program to control and manage non-communicable diseases (NCDs). Population screening is an integral component of this strategy and requires a substantial chunk of investment. Therefore, testing the screening program for economic along with clinical effectiveness is essential. There is significant proof of the benefits of incorporating economic evidence in health decision-making globally, although evidence from LMICs in NCD prevention is scanty. This systematic review aims to consolidate and synthesize economic evidence of screening programs for cardiovascular diseases (CVD) and diabetes from LMICs. The study protocol is registered on PROSPERO (CRD42021275806). The review includes articles from English and Chinese languages. An initial search retrieved a total of 2,644 potentially relevant publications. Finally, 15 articles (13 English and 2 Chinese reports) were included and scrutinized in detail. We found 6 economic evaluations of interventions targeting cardiovascular diseases, 5 evaluations of diabetes interventions, and 4 were combined interventions, i.e., screening of diabetes and cardiovascular diseases. The study showcases numerous innovative screening programs that have been piloted, such as using mobile technology for screening, integrating non-communicable disease screening with existing communicable disease screening programs, and using community health workers for screening. Our review reveals that context is of utmost importance while considering any intervention, i.e., depending on the available resources, cost-effectiveness may vary-screening programs can be made universal or targeted just for the high-risk population.

How do diverse low-income and middle-income countries implement primary healthcare team integration to support the delivery of comprehensive primary health care? A mixed-methods study protocol from India, Mexico and Uganda.

INTRODUCTION: Attainment of universal health coverage is feasible via strengthened primary health systems that are comprehensive, accessible, people-centred, continuous and coordinated. Having an adequately trained, motivated and equipped primary healthcare workforce is central to the provision of comprehensive primary healthcare (CPHC). This study aims to understand PHC team integration, composition and organisation in the delivery of CPHC in India, Mexico and Uganda. METHODS AND ANALYSIS: A parallel, mixed-methods study (integration of quantitative and qualitative results) will be conducted to gain an understanding of PHC teams. Methods include: (1) Policy review on PHC team composition, organisation and expected comprehensiveness of PHC services, (2) PHC facility review using the WHO Service Availability and Readiness Assessment, and (3) PHC key informant interviews. Data will be collected from 20, 10 and 10 PHCs in India, Mexico and Uganda, respectively, and analysed using descriptive methods and thematic analysis approach. Outcomes will include an in-depth understanding of the health policies for PHC as well as understanding PHC team composition, organisation and the delivery of comprehensive PHC. ETHICS AND DISSEMINATION: Approvals have been sought from the Institutional Ethics Committee of The George Institute for Global Health, India for the Indian sites, School of Medicine Research Ethics Committee at Makerere University for the sites in Uganda and the Research, Ethics and Biosecurity Committees of the Mexican National Institute of Public Health for the sites in Mexico. Results will be shared through presentations with governments, publications in peer-reviewed journals and presentations at conferences.

Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.

Importance: Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. Objective: To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. Design, Setting, and Participants: This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. Interventions: A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. Main Outcomes and Measures: The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. Results: A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. Conclusions and Relevance: This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.

Thickening of Ectatic Cornea through Regeneration Using Decellularized Corneal Matrix Injectable Hydrogel: A Strategic Advancement to Mitigate Corneal Ectasia.

Ectatic corneal diseases are a group of eye disorders characterized by progressive thinning and outward bulging of the cornea, resulting in vision impairment. A few attempts have been made to use cornea-derived extracellular matrix hydrogels for corneal tissue engineering; however, no studies have investigated its application in corneal ectasia. In this study, we have first developed an animal surgical model that mimics a few specific phenotypes of ectatic cornea. Later, we investigated the potential of decellularized cornea matrix hydrogels (dCMH) from both human and bovine sources in increasing the thickness of the cornea in the developed surgical model. Our data advocate that surgical stromal depletion can be followed to establish ectatic models and can also provide information on the biocompatibility of materials, its integration with native stroma, degradation over time, and tissue remodeling. We observed that dCMH from both sources could integrate with ectatic thin corneal stroma and helps in regaining the thickness by regenerating a reasonably functional and transparent stroma; however, no significant difference was spotted between the dCMH made from human and bovine corneal tissue sources. Hence, this study is a promising step toward developing a non-invasive technique for the treatment of corneal ectasia by using dCMH.