Enzymatic and Non-enzymatic Collagen Cross-Links and Fracture Occurrence in Type 1 Diabetes Patients.

Increased fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD) by DXA. Advanced glycation end-products (AGEs) have been implicated in the increased fracture risk in T1D, yet recent publications question this. To test the hypothesis that enzymatic collagen cross-links rather than AGEs correlate with fracture incidence in T1D, we analyzed iliac crest biopsies from sex-matched, fracturing T1D patients (N = 5; T1DFx), 6 non-fracturing T1D patients (T1DNoFx), and 6 healthy subjects, by Raman microspectroscopy as a function of tissue age (based on double fluorescent labels), in intracortical and trabecular bone, to determine pyridinoline (Pyd), ε-N-Carboxymethyl-L-lysine, and pentosidine (PEN)). There were no differences in the clinical characteristics between the T1DFx and T1DNoFx groups. At trabecular forming surfaces, T1DFx patients had higher PEN and Pyd content compared to T1DNoFx ones. Previous studies have shown that elevated PEN does not necessarily correlate with fracture incidence in postmenopausal, long-term T1D patients. On the other hand, the elevated Pyd content in the T1DFx patients would be consistent with published studies showing a significant correlation between elevated trivalent enzymatic collagen cross-links and fracture occurrence independent of BMD. Collagen fibers with high Pyd content are more brittle. Thus, a plausible suggestion is that it is the enzymatic collagen cross-links that either by themselves or in combination with the adverse effects of increased AGE accumulation that result in fragility fracture in T1D.

Cellulose Degradation Enzymes in Filamentous Fungi, A Bioprocessing Approach Towards Biorefinery.

The economic exploration of renewable energy resources has hot fundamentals among the countries besides dwindling energy resources and increasing public pressure. Cellulose accumulation is a major bio-natural resource from agricultural waste. Cellulases are the most potential enzymes that systematically degrade cellulosic biomass into monomers which could be further processed into several efficient value-added products via chemical and biological reactions including useful biomaterial for human benefits. This could lower the environmental risks problems followed by an energy crisis. Cellulases are mainly synthesized by special fungal genotypes. The strain Trichoderma orientalis could highly express cellulases and was regarded as an ideal strain for further research, as the genetic tools have found compatibility for cellulose breakdown by producing effective cellulose-degrading enzymes. This strain has found a cellulase production of about 35 g/L that needs further studies for advancement. The enzyme activity of strain Trichoderma orientalis needed to be further improved from a molecular level which is one of the important methods. Considering synthetic biological approaches to unveil the genetic tools will boost the knowledge about commercial cellulases bioproduction. Several genetic transformation methods were significantly cited in this study. The transformation approaches that are currently researchers are exploring is transcription regulatory factors that are deeply explained in this study, that are considered essential regulators of gene expression.

Impact of the Syrian conflict and forced displacement on respiratory health: an analysis of primary data from a humanitarian organisation.

BACKGROUND: Despite a decade of conflict, there has been little exploration of respiratory health in Syria, notwithstanding the known impacts of conflict on lung health. Our aim is to explore the burden and trends of respiratory consultations in Syrian American Medical Society (SAMS) facilities in northwest Syria through an ecological analysis. METHODS: We performed a retrospective review of routinely collected data relating to respiratory presentations in SAMS' facilities between March 2017 and June 2020; we compared data by facility type, infectious versus non-infectious aetiologies and age. RESULTS: Data were available for 5 058 864 consultations, of which 1 228 722 (24%) were respiratory presentations, across 22 hospitals, 22 primary healthcare centres, 3 mobile clinics and 1 polyclinic. The median number of respiratory consultations per month was 30 279 (IQR: 25 792-33 732). Key findings include: 73% of respiratory consultations were for children; respiratory presentations accounted for up to 38% of consultations each month, seasonal variation was evident; respiratory tract infections accounted for 91% of all respiratory presentations. A steep decrease in consultations occurred between the end of 2019 (160 000) and the first quarter of 2020 (90 000), correlating with an escalation of violence in Idlib governorate. CONCLUSION: This study presents the largest quantitative analysis of respiratory data collected during the Syrian conflict. It supports the need for improved measures to aid the prevention, diagnosis and management of respiratory conditions during conflict as well as further research to explore the impact of conflict on respiratory health.

Bone intrinsic material and compositional properties in postmenopausal women diagnosed with long-term Type-1 diabetes.

The incidence of diabetes mellitus and the associated complications are growing worldwide, affecting the patients' quality of life and exerting a considerable burden on health systems. Yet, the increase in fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD), leading to the hypothesis that alterations in bone quality are responsible for the increased risk. Material/compositional properties are important aspects of bone quality, yet information on human bone material/compositional properties in T1D is rather sparse. The purpose of the present study is to measure both the intrinsic material behaviour by nanoindentation, and material compositional properties by Raman spectroscopy as a function of tissue age and microanatomical location (cement lines) in bone tissue from iliac crest biopsies from postmenopausal women diagnosed with long-term T1D (N = 8), and appropriate sex-, age-, BMD- and clinically-matched controls (postmenopausal women; N = 5). The results suggest elevation of advanced glycation endproducts (AGE) content in the T1D and show significant differences in mineral maturity / crystallinity (MMC) and glycosaminoglycan (GAG) content between the T1D and control groups. Furthermore, both hardness and modulus by nanoindentation are greater in T1D. These data suggest a significant deterioration of material strength properties (toughness) and compositional properties in T1D compared with controls.

High-Output Heart Failure in a Patient With Klippel-Trénaunay Syndrome: A Case Report.

Klippel-Trénaunay syndrome (KTS) is a rare and complex congenital syndrome defined as the triad of cutaneous capillary malformation, bone and soft tissue hypertrophy, and venous and lymphatic malformations. KTS is thought to be due to a somatic mutation in phosphatidyl-inositol 3 kinase. It belongs to a group of syndromes termed the PI3CA-Related Overgrowth Spectrum (PROS) disorders. Because of the rarity and clinical heterogeneity of these disorders, management is patient specific, and best evidence guidelines are lacking. The most common clinical complications are thromboembolism, thrombophlebitis, pain, bleeding, and high-output heart failure. Surgery is recommended for hemangiomas and chronic venous insufficiency. The early identification of children with PROS disorders has allowed treatment with mTOR inhibitors which have been shown to be effective. The recent development of a direct PI3K inhibitor (alpelisib) has shown promise in preventing abnormal growth and long-term complications of KTS. This report documents a case of high-output heart failure due to the vascular malformations associated with KTS in a 57-year-old male patient and discusses current literature regarding the management of KTS with inhibitors of mTOR and PI3KCA.

Protracted armed conflict and maternal health: a scoping review of literature and a retrospective analysis of primary data from northwest Syria.

INTRODUCTION: Syria's protracted conflict has devastated the health system reversing progress made on maternal health preconflict. Our aim is to understand the state of maternal health in Syria focused on underage pregnancy and caesarean sections using a scoping review and quantitative analysis; the latter draws on data from the Syrian American Medical Society's (SAMS) maternal health facilities in northwest Syria. METHODS: We performed a scoping review of academic and grey literature on the state of maternal health across Syria since the onset of conflict (taken as March 2011). Identified articles were screened using pre-established criteria and themes identified. We also performed a retrospective quantitative analysis of maternal health data from SAMS' facilities in a microcontext in north-west Syria between March 2017 and July 2020, analysing the trends in the proportion of births by caesarean section and age at pregnancy. RESULTS: Scoping review: of 2824 articles, 21 remained after screening. Main themes related to maternal mortality rates, caesarean sections, maternal age and perinatal care. 12 studies reported caesarean section rates; these varied from 16% to 64% of all births: northern Syria (19%-45%,) Damascus (16%-54%,) Lattakia (64%) and Tartous (59%.) Quantitative analysis: Of 77 746 births across 17 facilities, trend data for caesarean sections showed a decrease from 35% in March 2017 to 23% in July 2020 across SAMS facilities. Girls under 18 years accounted for 10% of births and had a lower proportion of caesarean section births. There was notable geographical and interfacility variation in the findings. CONCLUSION: The quality of available literature was poor with country-level generalisations. Research which explores microcontexts in Syria is important given the different effects of conflict across the country and the fragmented health system. Our quantitative analysis provides some evidence around the changes to caesarean section rates in northwest Syria. Despite limitations, this study adds to sparse literature on this important topic.

A pilot study on the nanoscale properties of bone tissue near lacunae in fracturing women.

The goal of this study is to investigate the causes of osteoporosis-related skeletal fragility in postmenopausal women. We hypothesize that bone fragility in these individuals is largely due to mineral, and/or intrinsic material properties in the osteocyte lacunar/peri-lacunar regions of bone tissue. Innovative measurements with nanoscale resolution, including scanning electron microscope (SEM), an atomic force microscope that is integrated with infrared spectroscopy (AFM-IR), and nanoindentation, were used to characterize osteocyte lacunar and peri-lacunar properties in bone biopsies from fracturing (Cases) and matched (Age, BMD), non-fracturing (Controls) postmenopausal healthy women. In the peri-lacunar space, the nanoindentation results show that the modulus and hardness of the Controls are lower than the Cases. The AFM-IR results conclusively show that the mineral matrix, maturity (peak) (except in outer/far regions in Controls) were greater in Controls than in Cases. Furthermore, these results indicate that while mineral-to-matrix area ratio tend to be greater, the mineral maturity and crystallinity peak ratio "near" lacunae is greater than at regions "far" or more distance from lacunae in the Controls only. Due to the heterogeneity of bone structure, additional measurements are needed to provide more convincing evidence of altered lacunar characteristics and changes in the peri-lacunar bone as mechanisms related to postmenopausal women and fragility. Such findings would motivate new osteocyte-targeted treatments to reduce fragility fracture risks in these groups.

Prospecting cellulose fibre-reinforced composite membranes for sustainable remediation and mitigation of emerging contaminants.

Many environmental pollutants caused by uncontrolled urbanization and rapid industrial growth have provoked serious concerns worldwide. These pollutants, including toxic metals, dyes, pharmaceuticals, pesticides, volatile organic compounds, and petroleum hydrocarbons, unenviably compromise the water quality and manifest a severe menace to aquatic entities and human beings. Therefore, it is of utmost importance to acquaint bio-nanocomposites with the capability to remove and decontaminate this extensive range of emerging pollutants. Recently, considerable emphasis has been devoted to developing low-cost novel materials obtained from natural resources accompanied by minimal toxicity to the environment. One such component is cellulose, naturally the most abundant organic polymer found in nature. Given bio-renewable sources, natural abundance, and impressive nanofibril arrangement, cellulose-reinforced composites are widely engineered and utilized for multiple applications, such as wastewater decontamination, energy storage devices, drug delivery systems, paper and pulp industries, construction industries, and adhesives, etc. Environmental remediation prospective is among the fascinating application of these cellulose-reinforced composites. This review discusses the structural attributes of cellulose, types of cellulose fibrils-based nano-biocomposites, preparatory techniques, and the potential of cellulose-based composites to remediate a diverse array of organic and inorganic pollutants in wastewater.

Remarkable non-linear optical properties of gold cluster doped graphyne (GY): A DFT study.

The nonlinear optical (NLO) properties of gold (Au) doped graphyne (GY) complexes are the subject of this quantum mechanical investigation. Detailed profiling of GY@Aucenter, GY@Auside, GY@2Auabove,GY@2Auperpendicular, and GY@3Aucenter is accomplished at CAM-B3LYP/LANL2DZ. The differential influence of various GY based complexes on molecular geometry, vertical ionization energy (VIE), interaction energy (Eint), frontier molecular orbitals (FMOs), density of states (DOS), absorption maximum (λmax), molecular electrostatic potential (MEP), electron density distribution map (EDDM), transition density matrix (TDM), dipole moment (µ) and non-linear optical (NLO) properties have been investigated. Non-covalent interaction (NCI) analysis has been done to explore the sort of interactions in designed complexes. The vibrational frequencies are probed via infrared (IR) analysis. Doping tactics in all complexes dramatically changed charge carrier properties, such as shrinking band gap (Eg) and increasing λmax in the range of 3.97-5.58 eV and 288-562 nm respectively, compared to pure GY with 5.78 eV Eg and 265 nm λmax. When compared to GY (αO = 281.54 andßO = 0.21 au), GY@3Aucenter exhibited a significant increase in static mean polarizability (αO = 415 au) and the mean first hyperpolarizability (ßo = 3652 au) attributable to its lowest excitation energy (ΔE). GY doping has been discovered to be advantageous for designing potential nanoscale devices by focusing on the symphony between small Au clusters and GY and their impacts on NLO aspects.

Ab initio study for superior sensitivity of graphyne nanoflake towards nitrogen halides over ammonia.

Graphyne (GYN) has received immense attention in gas adsorption applications due to its large surface area. The adsorption of toxic ammonia and nitrogen halides gaseous molecules on graphyne has been theoretically studied at ωB97XD/6-31 + G(d, p) level of DFT. The counterpoise corrected interaction energies of NH3, NF3, NCl3, and NBr3 molecules with GYN are - 4.73, - 2.27, - 5.22, and - 7.19 kcal mol-1, respectively. Symmetry-adapted perturbation theory (SAPT0) and noncovalent interaction index (NCI) reveal that the noncovalent interaction between analytes and GYN is dominated by dispersion forces. The significant change in electronic behavior, i.e., energies of HOMO and LUMO orbitals and NBO charge transfer correspond to the pronounced sensitivity of GYN towards considered analytes, especially NBr3. Finally, TD-DFT calculation reveals a decrease in electronic transition energies and shifting of adsorption to a longer wavelength. The recovery time for NX3@GYN is observed in nanoseconds, which is many orders of magnitude smaller than the reported systems. The recovery time is further decreased with increasing temperature, indicating that the GYN benefits from a short recovery time as a chemical sensor.

Optimization of Monolayer MoS2 with Prescribed Mechanical Properties.

Various technological challenges are essentially material problems in our times. New functional and functional graded nanomaterials are constructed of components with predefined properties. The design of nanostructures with predefined mechanical properties was considered in this paper. This study applies the evolutionary algorithm (EA) to the optimization problem in the design of nanomaterials. The optimal design combined EA with molecular dynamics to identify the size of the void for the prescribed elastic properties in monolayer 2D MoS2 nanostructures. The numerical results show that the proposed EA and the use of optimization method allowed accurately obtaining nanostructures with predefined mechanical material properties by introducing elliptical voids in the 2D MoS2 nanosheets.

Same day discharge following non-elective PCI for non-ST elevation acute coronary syndromes.

BACKGROUND AND AIM: Timing of discharge after percutaneous coronary intervention (PCI) is a crucial aspect of procedural safety and patient turnover. We examined predictors and outcomes of same-day discharge (SDD) after non-elective PCI for non-ST elevation acute coronary syndromes (NSTE-ACS) in comparison with next-day discharge (NDD). METHODS: Baseline demographic, clinical, and procedural data were collected as were in-hospital outcomes and post-PCI length of stay (LOS) for all patients undergoing non-elective PCI for NSTE-ACS between 2011 and 2014 at a central tertiary care center. Thirty day and 1-year mortality and bleeding as well as 30-day readmission rates were determined from social security record and medical chart review. Logistic regression was performed to identify predictors of SDD, and propensity-matched analysis was done to examine the differences in outcomes between NDD and SDD. RESULTS: Out of 2,529 patients who underwent non-elective PCI for NSTE-ACS from 2011 to 2014, 1,385 met the inclusion criteria (mean age = 63 years; 26% women) and were discharged either the same day of (N = 300) or the day after (N = 1,085) PCI. Thirty-day and one-year mortality and major bleeding rates were similar between the 2 groups. Logistic regression identified male sex, radial access, negative troponin biomarker status, and procedure start time as predictors of SDD. In propensity-matched analyses, there was no difference in 30-day mortality and readmission between SDD and NDD groups. CONCLUSIONS: SDD after non-elective PCI for NSTE-ACS may be a reasonable alternative to NDD for selected low-risk patients with comparable mortality, bleeding, and readmission rates.

Osteocyte Wnt/ß-catenin pathway activation upon mechanical loading is altered in ovariectomized mice.

Estrogen levels decline in both sexes with age, but more dramatically in females. Activation of the Wnt/ß-catenin signaling pathway is central to the regulation of bone mass accrual and maintenance and in response to mechanical loading. Using the ovariectomized mouse model we examined the effect of estrogen loss on the osteocyte's ability to activate the Wnt/ß-catenin pathway following mechanical loading. Female TOPGAL mice underwent ovariectomy (OVX) (n = 10) or sham surgery (n = 10) at 16 weeks of age. Four weeks post-surgery, a single loading session (global strain of 2200 µÎµ for 100 cycles at 2 Hz) was performed on the right forearm with the left as a non-loaded control. Mice (n = 5) were sacrificed at 1 or 24 hr post-load. Ulnae were stained for ß-catenin activation, femurs were used for µCT and 3-pt bending/biomechanical testing, and tibiae were used for histology analysis and to determine osteocyte lacunar size using SEM and high resolution micro-XCT. A 2.2-fold increase in ß-catenin signaling activation was observed 24 hr post-load in the Sham group but did not occur in the OVX group. The OVX group versus control had significant losses (p < 0.05) in trabecular BMD (-8%), BV/TV (-35%) and thickness (-23%), along with cortical thickness (-6%) and periosteal perimeter (-4%). The OVX group had significantly higher trabecular bone osteoclast numbers (63%), OCS/BS (77%) and N.OC/BPm (94%) and a significant decrease in osteoblast number (53%), OBS/BS (37%) and N.OB/BPm (40%) compared to the sham group (p < 0.05). Cortical bone lacunar number/lacunar volume and bone biomechanical properties did not change between groups. Given that the ulna is a cortical bone loading model and the lack of changes in osteocyte lacunar number/volume in cortical bone, which would alter strains experienced by osteocytes, these data suggest the absence of estrogen resulted in intrinsic changes in the ability of the osteocyte to respond to mechanical load, rather than changes in the biomechanical and architectural properties of bone.

Electrochemical sensing behavior of graphdiyne nanoflake towards uric acid: a quantum chemical approach.

Though the gas sensing applications of graphdiyne have widely reported; however, the biosensing utility of graphdiyne needs to be explored. This study deals with the sensitivity of graphdiyne nanoflake (GDY) towards the uric acid (UA) within the density functional framework. The uric acid is allowed to interact with graphdiyne nanoflake from all the possible orientations. Based on these interacting geometries, the complexes are differentiated with naming, i.e., UA1@GDY, UA2@GDY, UA3@GDY, and UA4@GDY (Fig. 1). The essence of interface interactions of UA on GDY is derived by computing geometric, energetic, electronic, and optical properties. The adsorbing affinity of complexes is evaluated at ωB97XD/6-31 + G(d, p) level of theory. The stabilities of the complexes are quantified through the interaction energies (Eint) with reasonable accuracy. The calculated Eint of the UA1@GDY, UA2@GDY, UA3@GDY, and UA4@GDY complexes are - 31.13, - 25.87, - 20.59, and - 16.54 kcal/mol, respectively. In comparison with geometries, it is revealed that the higher stability of complexes is facilitated by π-π stacking. Other energetic analyses including symmetry adopted perturbation theory (SAPT), noncovalent interaction index (NCI), and quantum theory of atoms in molecule (QTAIM) provide the evidence of dominating dispersion energy in stabilizing the resultant complexes. The HOMO-LUMO energies, NBO charge transfer, and UV-vis analysis justify the higher electronic transition in UA1@GDY, plays a role of higher sensitivity of GDY towards the π-stacked geometries over all other possible interaction orientations. The present findings bestow the higher sensitivity of GDY towards uric acid via π-stacking interactions. Fig. 1 Optimized geometries (with interaction distances in Å) of UA@GDY complexes.

Effect of substrate ratios on the simultaneous carbon, nitrogen, sulfur and phosphorous conversions in microbial fuel cells.

The columbic efficiency, removal efficiency and voltage production of seven different combinations of carbon (acetic acid, albumin and sucrose) with nutrients (C:N, C:P, C:S, C:N:S, C:P:S, C:N:P and C: N:S:P) were investigated at three different ratios (20:1, 15:1 and 10:1). The effects of various pH values were also explored for these combinations of carbon, and sulfur compounds (pH 6-8). The highest columbic efficiency (75.8%), COD removal efficiency (86%) and voltage (667 mV) were recorded when the acetic acid was used in the MFC and the lowest columbic efficiency (12.8%), removal efficiency (37.6%) and voltage (145 mV) were observed in case of albumin. A marked increase in columbic efficiency, removal efficiency and voltage production were seen with the rise in the pH value from 6 to 8. The lowest columbic efficiency, removal efficiency and voltage production were seen at pH 6 and highest at pH 8. At each investigated pH, the highest removal efficiency, columbic efficiency, and voltage were found at substrate ratio of 20:1 while lower at 10:1. At all pH values, the carbon to nutrient ratios seemed to have followed a similar trend i.e., the COD removal efficiency, columbic efficiency and voltage generation was found in the order C:N > C:N:S > C:N:S:P > C:N:P > C:S > C:P:S > C:P. In all cases, nitrogen showed a higher removal as compared to phosphorous and sulfur.

Altered collagen chemical compositional structure in osteopenic women with past fractures: A case-control Raman spectroscopic study.

Incidences of low-trauma fractures among osteopenic women may be related to changes in bone quality. In this blinded, prospective-controlled study, compositional and heterogeneity contributors of bone quality to fracture risk were examined. We hypothesize that Raman spectroscopy can differentiate between osteopenic women with one or more fractures (cases) from women without fractures (controls). This study involved the Raman spectroscopic analysis of cortical and cancellous bone composition using iliac crest biopsies obtained from 59-cases and 59-controls, matched for age (62.0 ± 7.5 and 61.7 ± 7.3 years, respectively, p = 0.38) and hip bone mineral density (BMD, 0.827 ± 0.083 and 0.823 ± 0.072 g/cm3, respectively, p = 0.57). Based on aggregate univariate case-control and odds ratio based logistic regression analyses, we discovered two Raman ratiometric parameters that were predictive of past fracture risk. Specifically, 1244/1268 and 1044/959 cm-1 ratios, were identified as the most differential aspects of bone quality in cortical cases with odds ratios of 0.617 (0.406-0.938 95% CI, p = 0.024) and 1.656 (1.083-2.534 95% CI, p = 0.020), respectively. Both 1244/1268 and 1044/959 cm-1 ratios exhibited moderate sensitivity (59.3-64.4%) but low specificity (49.2-52.5%). These results suggest that the organization of mineralized collagen fibrils were significantly altered in cortical cases compared to controls. In contrast, compositional and heterogeneity parameters related to mineral/matrix ratios, B-type carbonate substitutions, and mineral crystallinity, were not significantly different between cases and controls. In conclusion, a key outcome of this study is the significant odds ratios obtained for two Raman parameters (1244/1268 and 1044/959 cm-1 ratios), which from a diagnostic perspective, may assist in the screening of osteopenic women with suspected low-trauma fractures. One important implication of these findings includes considering the possibility that changes in the organization of collagen compositional structure plays a far greater role in postmenopausal women with osteopenic fractures.

Using a low-cost, real-time electronic immunization registry in Pakistan to demonstrate utility of data for immunization programs and evidence-based decision making to achieve SDG-3: Insights from analysis of Big Data on vaccines.

BACKGROUND: Despite the proliferation of digital interventions such as Electronic Immunization Registries (EIR), currently, there is little evidence regarding the use of EIR data to improve immunization outcomes in resource-constrained settings. To achieve the Sustainable Development Goal (SDG) of ensuring healthy lives and well-being for all ages, particularly for newborns and children under the age of 5 (goal 3b), it is essential to generate and use quality data for evidence-based decision making to overcome barriers inherent in immunization systems. In Pakistan, only 66 % of children receive all basic vaccinations, and in Sindh province, the number is even lower at 49 %. In 2012, IRD developed and piloted Zindagi Mehfooz (Safe Life; ZM) ElR, an Android-based platform that records and analyses individual-level child data in real-time. In 2017 in collaboration with Expanded Programme for Immunization (EPI) Sindh, ZM was scaled-up across the entire Sindh province and is currently being used by 2521 government vaccinators in 1539 basic health facilities, serving >48 million population. OBJECTIVE: The study aims to demonstrate how big immunization data from the ZM-EIR is being leveraged in Sindh, Pakistan for actionable decision making via three use cases (a) improving performance management of vaccinators to increase geographical coverage, (b) quantifying the impact of provincial accelerated outreach activities, and (c) examining the impact of the COVID-19 pandemic on routine immunization coverage to help devise a tailored approach for future efforts. METHODS: From October 2017 to April 2020, more than 2.9 million children and 0.9 million women have been enrolled, and more than 22 million immunization events have been recorded in the ZM-EIR. We extracted de-identified data from ZM-EIR for January 1, 2019 - April 20, 2020, period. Given the needs of each use case, monthly and daily indicators on vaccinator performance (attendance and compliance), daily immunization visits, and the number of antigens administered were calculated. Geo-coordinate data of antigen administration was extracted and displayed on geographic maps using QGIS. All generated reports were shared at fixed frequency with various stakeholders, such as partners at EPI-Sindh, for utilization in decision making and informing policy. RESULT: Our use-cases demonstrate the use of EIR data for data-driven decision making. From January - December 2019, the monthly monitoring of program indicators helped increase the vaccinator attendance from 44% to 88%, while an 85 % increase in geographical coverage was observed in a polio-endemic super high-risk union council (SHRUC) in Karachi. The analysis of daily average antigens administered during accelerated outreach efforts (AOE) as compared to routine activities showed an increase in average daily Pentavalent-3, Measles-1, and Measles-2 vaccines administered by 103%, 154%, and 180% respectively. These findings helped decide to continue the accelerated effort in high-risk areas (compared to the entire province) rather than discontinuing the activity due to high costs. During COVID-19 lockdown, the daily average number of child immunizations reduced from 16,649 to 4335 per day, a decline of 74% compared to 6 months preceding COVID-19 lockdown. ZM-EIR data is currently helping to shape the planning and implementation of critical strategies to mitigate the impact of the COVID-19 pandemic. CONCLUSION: The big data for vaccines generated through EIRs is a powerful tool to monitor immunization work-force and ensure chronically missed communities are identified and covered through targeted strategies. Geospatial data availability and analysis is changing the way EPI review meetings occur with stakeholders, taking data-driven decisions for better planning and resource allocation. In the fight against COVID-19 pandemic, as governments gradually begin to shift from containing the outbreak to strategizing a plan for sustaining the essential health services, the countries that will emerge most successful are likely the ones who can best use technology and real-time data for targeted efforts.

Impact of COVID-19 pandemic response on uptake of routine immunizations in Sindh, Pakistan: An analysis of provincial electronic immunization registry data.

BACKGROUND: COVID-19 pandemic has affected routine immunization globally. Impact will likely be higher in low and middle-income countries with limited healthcare resources and fragile health systems. We quantified the impact, spatial heterogeneity, and determinants for childhood immunizations of 48 million population affected in the Sindh province of Pakistan. METHODS: We extracted individual immunization records from real-time provincial Electronic Immunization Registry from September 23, 2019, to July 11, 2020. Comparing baseline (6 months preceding the lockdown) and the COVID-19 lockdown period, we analyzed the impact on daily immunization coverage rate for each antigen by geographical area. We used multivariable logistic regression to explore the predictors associated with immunizations during the lockdown. RESULTS: There was a 52.5% decline in the daily average total number of vaccinations administered during lockdown compared to baseline. The highest decline was seen for Bacille Cal-mette Guérin (BCG) (40.6% (958/2360) immunization at fixed sites. Around 8438 children/day were missing immunization during the lockdown. Enrollments declined furthest in rural districts, urban sub-districts with large slums, and polio-endemic super high-risk sub-districts. Pentavalent-3 (penta-3) immunization rates were higher in infants born in hospitals (RR: 1.09; 95% CI: 1.04-1.15) and those with mothers having higher education (RR: 1.19-1.50; 95% CI: 1.13-1.65). Likelihood of penta-3 immunization was reduced by 5% for each week of delayed enrollment into the immunization program. CONCLUSION: One out of every two children in Sindh province has missed their routine vaccinations during the provincial COVID-19 lockdown. The pool of un-immunized children is expanding during lockdown, leaving them susceptible to vaccine-preventable diseases. There is a need for tailored interventions to promote immunization visits and safe service delivery. Higher maternal education, facility-based births, and early enrollment into the immunization program continue to show a positive association with immunization uptake, even during a challenging lockdown.