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Divya Kumari,1,* Lubna Sheikh,1,* Soumya Bhattacharya,1,* Thomas J Webster,2 Suprabha Nayar1 1Materials Science and Technology Division, CSIR-National Metallurgical Laboratory, Burmamines, Jamshedpur, India; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: In this study, natural graphite was first converted to collagen-graphene composites and then used as templates for the synthesis of nanoparticles of silver, iron oxide, and hydroxyapatite. X-ray diffraction did not show any diffraction peaks of graphene in the composites after inorganic nucleation, compared to the naked composite which showed (002) and (004) peaks. Scanning electron micrographs showed lateral gluing/docking of these composites, possibly driven by an electrostatic attraction between the positive layers of one stack and negative layers of another, which became distorted after inorganic nucleation. Docking resulted in single layer-like characteristics in certain places, as seen under transmission electron microscopy, but sp2/sp3 ratios from Raman analysis inferred three-layer composite formation. Strain-induced folding of these layers into uniform clusters at the point of critical nucleation, revealed beautiful microstructures under scanning electron microscopy. Lastly, cell viability studies using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed the highest cell viability for the collagen-graphene-hydroxyapatite composites. In this manner, this study provided – to the field of nanomedicine – a new process for the synthesis of several nanoparticles (with low toxicity) of high interest for numerous medical applications. Keywords: composites, graphene, collagen, lateral gluing, and inorganic nanoparticles

Dan Hoff,1 Lubna Sheikh,2 Soumya Bhattacharya,2 Suprabha Nayar,2 Thomas J Webster11School of Engineering, Brown University, Providence, RI, USA; 2Biomaterials Group, Materials Science and Technology Division, CSIR-National Metallurgical Laboratory, Burmamines, Jamshedpur, IndiaAbstract: In the present study, the permeability of 11 different iron oxide nanoparticle (IONP) samples (eight fluids and three powders) was determined using an in vitro blood–brain barrier model. Importantly, the results showed that the ferrofluid formulations were statistically more permeable than the IONP powder formulations at the blood–brain barrier, suggesting a role for the presently studied in situ synthesized ferrofluid formulations using poly(vinyl) alcohol, bovine serum albumin, collagen, glutamic acid, graphene, and their combinations as materials which can cross the blood–brain barrier to deliver drugs or have other neurological therapeutic efficacy. Conversely, the results showed the least permeability across the blood–brain barrier for the IONP with collagen formulation, suggesting a role as a magnetic resonance imaging contrast agent but limiting IONP passage across the blood–brain barrier. Further analysis of the data yielded several trends of note, with little correlation between permeability and fluid zeta potential, but a larger correlation between permeability and fluid particle size (with the smaller particle sizes having larger permeability). Such results lay the foundation for simple modification of iron oxide nanoparticle formulations to either promote or inhibit passage across the blood–brain barrier, and deserve further investigation for a wide range of applications.Keywords: ferrofluids, iron oxide nanoparticles, permeability, blood–brain barrier

High-quality, equitable, and inclusive education is essential for both individual and societal advancement. Educators play a crucial role in enhancing educational standards through effective pedagogical practices. This study investigates the influence of learning theories on educators' pedagogical strategies. A survey was conducted with 1845 educators from various educational levels in Brunei Darussalam. While educators demonstrated an understanding of behaviorism and cognitive theories, the results revealed a pronounced preference for constructivism. This approach allows educators to relate prior learning experiences, foster collaborative engagement, and provide constructive feedback. Furthermore, the results indicated that demographic factors, including gender, age, subject area, and administrative duties, affected educators’ pedagogical beliefs. The results emphasize the need for tailored, inclusive, and subject-specific professional development for educators to improve educational standards and promote inclusivity.

Wind erosion is recognized as one of the main environmental issues and seriously threatens ecosystem services in the Yarlung Zangbo River basin (YZRB), southern Tibetan Plateau. Exploring the spatiotemporal dynamics and drivers of wind erosion is crucial for improving regional ecosystem services and sustainable development. This study was conducted to examine the spatiotemporal patterns of soil wind erosion modulus (SWEM) in YZRB from 1990 to 2020 by using the revised wind erosion equation (RWEQ) and to identify the influence of climate change and anthropogenic activities on wind erosion dynamics. The results showed that temporally, the overall SWEM presented a significant downward trend (−0.912 t·hm−2·a−1) and a continuous downward trend in the key implementation areas of ecological engineering. Spatially, the severe area of wind erosion is mainly concentrated in the flat and broad river valley, where sand sources are widely distributed. Significant SWEM differences were found among various land use/cover (LULC) types. Exceeding 90% reduction rates in SWEM occurred in forests, grasslands, and cultivated land. Additionally, the influence analysis showed that climate change was the dominant factor driving the variations in wind erosion due to the reduction of wind speed. By contrast, the contribution of anthropogenic activities is relatively less, accounting for 43.50% of wind erosion change, which closely matches the transfer of LULC to grassland and forest land with the implementation area of ecological engineering projects. This study provides useful information on the driving mechanism of wind erosion, prevention service changes, and determining priority zones for desertification prevention in YZRB. We suggest that eco-restoration activities should be endorsed in the future, as well as the adaptive management that is required to control wind erosion and improve ecosystem services and human well-being for people in the YZRB region.

In this study, zircon grains are applied for U–Pb dating, Hf isotopes and trace elements to reveal the origin of magmatism and tectonic evolution of Late Paleozoic rocks of the Indian plate, Northern Pakistan. Most of the zircons are characterized by oscillatory zoning, depletion of light rare earth elements (LREE) and enrichment of heavy rare earth elements (HREE) with Ce and Eu anomalies. The yielded ages for these rocks are 256 ± 1.9 Ma and are plotted in the zones defined for the continental setting with few deviated toward the mid-oceanic ridge and the oceanic arc setting. Deviated zircons are recognized as inherited zircons by displaying a high concentration of normalized primitive La and Pr values, while others are plotted in the continental zones. Rare earth elements (REE) and trace elements including Th, Hf, U, Nb, Sc and Ti discriminate Swat orthogneisses into the within plate setting and the inherited zircons are plotted in the orogenic or the arc-related setting. The LREE discriminated these zircons into a magmatic zone with inherited zircons deviated toward the hydrothermal zone. The temperature calculated for these rocks based on the Ti content in zircon ranges from 679 to 942°C. The εHf(t) ranging from −11.1 to +1.4 reveals that the origin is the continental crust with the minute input of the juvenile mantle.

Abstract Background We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine. Case presentation We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor size. It was decided to continue Cabergoline throughout pregnancy to ensure further reduction in tumor size until delivery and to hold Cabergoline during postpartum period to allow for an adequate interval of breastfeeding. At 37 weeks of gestation, the patient delivered a healthy baby. Conclusion We were able to safely treat macroprolactinemia in our patient during pregnancy with cabergoline. This case report contributes to the relatively meager data available which advocates the safety of cabergoline therapy in pregnant hyperprolactinemic patients.

Abstract Background Massive postpartum hemorrhage is a life threatening obstetric emergency. In order to prevent the complications associated with this condition, an organized and step-wise management protocol should be immediately initiated. Methods An evidence based management protocol for massive postpartum hemorrhage was implemented at Aga Khan University Hospital, Karachi, Pakistan after an audit in 2005. We sought to evaluate the compliance and outcomes associated with this management protocol 3 years after its implementation. A review of all deliveries with massive primary postpartum hemorrhage (blood loss ≥ 1500 ml) between January, 2008 to December, 2008 was carried out. Information regarding mortality, mode of delivery, possible cause of postpartum hemorrhage and medical or surgical intervention was collected. The estimation of blood loss was made via subjective and objective assessment. Results During 2008, massive postpartum hemorrhage occurred in 0.64% cases (26/4,052). No deaths were reported. The mean blood loss was 2431 ± 1817 ml (range: 1500 - 9000 ml). Emergency cesarean section was the most common mode of delivery (13/26; 50%) while uterine atony was the most common cause of massive postpartum hemorrhage (14/26; 54%). B-lynch suture (24%) and balloon tamponade (60%) were used more commonly as compared to our previously reported experience. Cesarean hysterectomy was performed in 3 cases (12%) for control of massive postpartum hemorrhage. More than 80% compliance was observed in 8 out of 10 steps of the management protocol. Initiation of blood transfusion at 1500 ml blood loss (89%) and overall documentation of management (92%) were favorably observed in most cases. Conclusion This report details our experience with the practical implementation of a management protocol for massive postpartum hemorrhage at a tertiary care hospital in a developing country. With the exception of arterial embolization, relatively newer, simpler and potentially safer techniques are now being employed for the management of massive postpartum hemorrhage at our institution. Particular attention should be paid to the documentation of the management steps while ensuring a stricter adherence to the formulated protocols and guidelines in order to further ameliorate patient outcomes in emergency obstetrical practice. More audits like the one we performed are important to recognize and rectify any deficiencies in obstetrical practice in developing countries. Dissemination of the same is pivotal to enable an open discourse on the improvement of existing obstetrical strategies.

Abstract Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, >1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6°/o of the patients in the intervention group, as compared with 4.3°/o of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.). [ABSTRACT FROM AUTHOR]

Introduction: There are numerous reasons for underutilization of the public health sector for surgery in Pakistan. This results in patients being diverted to private hospitals or tertiary care centers in urban areas. Diversions overburden the hospitals and significantly increase out-of-pocket costs for the patients. This study aims to determine the barriers to surgical care in first-level hospitals in Pakistan's Sindh province., Methods: We conducted a concurrent nested mixed methods study from May to June 2021 in public sector first-level hospitals in the Sindh province. Fifteen hospitals in six districts were surveyed. A consolidated hospital assessment tool adapted from the World Health Organization's Tool for Situational Analysis to Assess Emergency and Essential Surgical Care was used for quantitative data collection. Interview guides were developed for staff interviews., Results: Availability of trained staff was found to be the biggest barrier to the provision of safe surgery. Only eight hospitals had a general surgeon, anesthesiologist, and obstetrician/gynecologist, while the remaining had 1-2 of the three disciplines. Thirteen hospitals had a functioning x-ray machine, while 14 facilities had functioning ultrasound machines with trained personnel to operate them. Only three facilities always had blood available for transfusion. The qualitative component corroborated that the biggest barrier to providing surgical care was the lack of human resources., Conclusions: The lack of human resources is difficult to overcome. We found evidence of task-shifting to medical officers and trainee anesthesiologists, but this is without discrete regulation and monitoring. Building surgical workforce capacity must be addressed in the interest of quality care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Over the past few decades, poly(methyl methacrylate) (PMMA) based bone cement has been clinically used extensively in orthopedics for arthroplasty and kyphoplasty, due to its biocompatibility and excellent primary fixation to the host bone. In this focused review, we discuss the use of various fillers and secondary chemical moieties to improve the bioactivity and the physicochemical properties. The viscosity of the PMMA blend formulations and working time are crucial to achieving intimate contact with the osseous tissue, which is highly sensitive to organic or inorganic fillers. Hydroxyapatite as a reinforcement resulted in compromised mechanical properties of the modified cement. The possible mechanisms of the additive- or filler-dependent strengthening or weakening of the PMMA blend are critically reviewed. The addition of layered double hydroxides with surface functionalization appears to be a promising approach to enhance the bonding of filler with the PMMA matrix. Such an approach consequently improves the mechanical properties, owing to enhanced dispersion as well as contributions from crack bridging. Finally, the use of emerging alternatives, such as nanoparticles, and the use of natural biomolecules were highlighted to improve bioactivity and antibacterial properties.

Objective This study aimed to assess the indirect impact of the COVID-19 pandemic on obstetric quality measures. Materials and methods This cross-sectional study was conducted at a private-sector tertiary care hospital in Karachi, Pakistan. Data were collected for specific antenatal, intrapartum, and postpartum care indicators during the initial six months of the COVID-19 phase (March to August 2020) and compared with baseline measures from the preceding six months before the COVID-19 phase (September 2019 to February 2020) using frequencies and percentages. Results During COVID-19, there was a 10% reduction (pre-COVID: 1041 and during COVID: 946) in outpatient obstetric volumes and a 65% increase (pre-COVID: 240 and during COVID: 396) in clinic cancellations, indicating a decreased influx of antenatal patients. Teleclinics served 8.3% (1429/18279) of the total obstetric patients during this period. Marginal decreases were observed in spontaneous vaginal deliveries 1358 (44%) vs 1049 (42.4%) and labor induction rates 818 (26.6%) vs 606 (24.2%). Additionally, there was a slight increase in instrumental deliveries, 121 (3.9%) vs 114 (4.6%) during the COVID phase. However, these changes were not statistically significant. Similarly, no substantial impact was observed on elective and emergency C-sections. Notably, there were more cases of primary postpartum hemorrhage (PPH) during the COVID-19 phase 36 (1.17%) vs 46 (1.86%), and these changes were statistically significant (p= 0.035). Similar trends were observed for eclampsia (p =0.05) and preeclampsia cases (p-value 0.074). However, other maternal morbidity indicators and intrauterine fetal deaths remained relatively unchanged. NICU admissions increased significantly (p=0.001), while early neonatal deaths remained unaffected. Patient satisfaction rates remained steady for inpatients and improved for outpatients during COVID-19. Conclusion The COVID-19 pandemic primarily affected antenatal volumes, neonatal admissions, and maternal morbidity indicators such as PPH, preeclampsia, and eclampsia. Despite the challenges, patient satisfaction and quality care standards were maintained during COVID-19 through new strategies and revised patient care processes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethical Review Board (ERC) of Aga Khan University Hospital issued approval reference # 2020-4910-11243. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shahwar et al.)

Over the past 3 decades, the diversity of ethnic, religious, and political backgrounds worldwide, particularly in countries of the Middle East and North Africa (MENA), has led to an increase in the number of intercountry conflicts and terrorist attacks, sometimes involving chemical and biological agents. This warrants moving toward a collaborative approach to strengthening preparedness in the region. In disaster medicine, artificial intelligence techniques have been increasingly utilized to allow a thorough analysis by revealing unseen patterns. In this study, the authors used text mining and machine learning techniques to analyze open-ended feedback from multidisciplinary experts in disaster medicine regarding the MENA region's preparedness for chemical, biological, radiological, and nuclear (CBRN) risks. Open-ended feedback from 29 international experts in disaster medicine, selected based on their organizational roles and contributions to the academic field, was collected using a modified interview method between October and December 2022. Machine learning clustering algorithms, natural language processing, and sentiment analysis were used to analyze the data gathered using R language accessed through the RStudio environment. Findings revealed negative and fearful sentiments about a lack of accessibility to preparedness information, as well as positive sentiments toward CBRN preparedness concepts raised by the modified interview method. The artificial intelligence analysis techniques revealed a common consensus among experts about the importance of having accessible and effective plans and improved health sector preparedness in MENA, especially for potential chemical and biological incidents. Findings from this study can inform policymakers in the region to converge their efforts to build collaborative initiatives to strengthen CBRN preparedness capabilities in the healthcare sector.

Background: Risk minimization measures (RMMs) are interventions intended to mitigate or prevent the occurrence of adverse reactions associated with medications. Having consistent measures across regulatory bodies (i.e., the Saudi Food and Drug Authority (SFDA), the United States Food and Drug Administration (US FDA), and the European Medicines Agency (EMA)) benefits medication use and safety and ultimately the patient., Objectives: This study aimed to investigate whether there is variability in these published RMMs between the three regulatory bodies., Methods: A specific data collection form was created to extract information from the SFDA's RMM list, US FDA's Risk Evaluation and Mitigation Strategy (REMS) list, and EMA's Risk Management Plan (RMP) list, as of February 2022 all RMMs that were available on the websites were reviewed. Medications with the same trade name were matched across regulators, and unmatched medications were checked for approval status. For medication groups such as NSAIDs in the SFDA's RMM list, they were matched by searching for the groups individually in the regulatory websites. All risks and types of minimizing measures were compared., Results: A total of 317 medications were retrieved from the SFDA's RMM list. The majority of medication classes were immunosuppressants (n = 60), antihypertensive (n = 33), and oncology medication (n = 29). There were only 62 medications with REMS from the US FDA website, a total of 14 medications were approved by the SFDA, and only nine medications were matched with the SFDA's RMM list. Also, there were 828 medications with RMP from the EMA website, a total of 334 has RMM, 128 are approved by the SFDA, and 71 matched with the SFDA's RMM list. Furthermore, seven medications were matched between SFDA, US FDA and EMA. After content review, four medications had similar risks and measures across the regulators and three medications had different risks and measures across the regulators. For the medication groups, a total of 36 groups were in the SFDA's list, 18 groups were matched with the US FDA, and 14 were matched with the EMA., Conclusions: Our study showed substantial differences among the regulatory authorities regarding RMMs. Harmony in published risk measures can have a significant impact on medication safety., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Antenatal Education equips parents with knowledge for safe maternal health and infant care. It also reduces fear and anxiety during childbirth. ANE curriculum can vary according to country and institute. It can include classes focusing on childbirth, pain relief techniques, mode of birth, parenting, breastfeeding, breathing techniques, etc. Although ANE is widely practiced in developed countries, there is no standard program in developing countries like Pakistan. This study aims to improve antenatal education at a tertiary care hospital in Karachi, Pakistan potentially proposing an upgraded curriculum as a national standard., Methods: This multiphase study used mix-method design was conducted in the Obstetrics and Gynaecology Department of a tertiary care hospital of Karachi, Pakistan from 2019 to 2021. Phase 1 of the study included reviewing and comparing the hospital's antenatal curriculum with existing literature, followed by Phase 2, which was a desk review of attendance and patient feedback. The 3 rd phase involved IDIs (in depth interviews) from health care workers (Obstetrics experts) to understand their perspectives regarding the ANE and the conducted classes. For phase one, gaps were identified and reported theoretically. For phase two, the annual attendance was recorded and participants' satisfaction with the classes assessed. Qualitative data from phase 2 and 3 was converted into themes and sub-themes., Results: The audit showed a decline in the attendance of antenatal classes due to the pandemic and consequent shift to online sessions. The low attendance in online courses could be attributed to various factors. Patient feedback was generally positive, with a majority expressing high satisfaction levels. Expert feedback highlighted the need for additional topics such as mental health and COVID in pregnancy, as well as fathers' involvement. The curriculum was updated to include these topics and made more interactive with printed handouts for parents., Conclusion: A standardized antenatal education covering various topics surrounding pregnancy, childbirth, and postnatal care must be available to parents nationwide., (© 2023. The Author(s).)

Objective: Maternal sepsis is the third leading cause of maternal mortality globally. WHO and collaborators developed a care bundle called FAST-M ( F luids, A ntibiotics, S ource identification and treatment, T ransfer and M onitoring) for early identification and management of maternal sepsis in low-resource settings. This study aimed to determine feasibility of FAST-M intervention in a low-resource setting in Pakistan. The FAST-M intervention consists of maternal sepsis screening tools, treatment bundle and implementation programme., Design and Setting: A feasibility study with before and after design was conducted in women with suspected maternal sepsis admitted at the Liaquat University of Medical and Health Sciences hospital Hyderabad. The study outcomes were compared between baseline and intervention phases. In the baseline phase (2 months), the existing sepsis care practices were recorded, followed by a training programme for healthcare providers on the application of FAST-M tools. These tools were implemented in the intervention phase (4 months) to assess any change in clinical practices compared with the baseline phase., Results: During the FAST-M implementation, 439 women were included in the study. 242/439 were suspected maternal infection cases, and 138/242 were women with suspected maternal sepsis. The FAST-M bundle was implemented in women with suspected maternal sepsis. Following the FAST-M intervention, significant changes were observed. Improvements were seen in the monitoring of oxygen saturation measurements (25.5% vs 100%; difference: 74%; 95% CI: 68.4% to 80.5%; p<0.01), fetal heart rate assessment (58% vs 100%; difference: 42.0%; 95% CI: 33.7% to 50.3%; p≤0.01) and measurement of urine output (76.5% vs 100%; difference: 23.5%; 95% CI: 17.6% to 29.4%; p<0.01). Women with suspected maternal sepsis received all components of the treatment bundle within 1 hour of sepsis recognition (0% vs 70.5%; difference: 70.5%; 95% CI: 60.4% to 80.6%; p<0.01)., Conclusion: Implementation of the FAST-M intervention was considered feasible and enhanced early identification and management of maternal sepsis at the study site., Trial Registration Number: ISRCTN17105658., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The World Health Organization and partners developed and evaluated a maternity-specific sepsis care bundle called 'FAST-M' for low-resource settings. However, this bundle has not yet been studied in Asia. Our study sought to evaluate the perceptions of healthcare providers about the implementation of the FAST-M intervention in Pakistan., Materials and Methods: The study was conducted at a public sector hospital in Hyderabad. We conducted three focus group discussions with healthcare providers including doctors, nurses, and healthcare administrators (n = 22) who implemented the FAST-M intervention. The Consolidated Framework for Implementation Research was used as a guiding framework for data collection and analysis. The data were analyzed using a thematic analysis approach and deductive methods., Results: Five overarching themes emerged: (I) FAST-M intervention and its significance including HCPs believing in the advantages of using the intervention to improve clinical practices; (II) Influence of outer and inner settings including non-availability of resources in the facility for sepsis care; (III) HCPs perceptions about sustainability, which were positive (IV) Integration into the clinical setting including HCPs views on the existing gaps, for example, shortage of HCPs and communication gaps, and their recommendations to improve these; and (V) Outcomes of the intervention including improved clinical processes and outcomes using the FAST-M intervention. Significant improvement in patient monitoring and FAST-M bundle completion within an hour of diagnosis of sepsis was reported by the HCPs., Conclusions: The healthcare providers' views were positive about the intervention, its outcomes, and long-term sustainability. The qualitative data provided findings on the acceptability of the overall implementation processes to support subsequent scaling up of the intervention., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

COVID-19 has disrupted the mental health services in 93% of the countries worldwide. Approximately 130 countries are affected catastrophically by COVID-19, which limits access to mental health services. Most vulnerable are children, pregnant women, and adults with limited access to mental healthcare. In highlighting the importance of mobilising resources, the WHO has given leaders around the world an opportunity to galvanise efforts. Maternal and children's mental health are crucial factors that may have a lifelong impact. In a post-pandemic world, a renewed focus is required to develop sustainable policies and action plans to support new mothers and new-borns in the first 1,000 days of life. This viewpoint shares a reflective discourse on contextualising the need of investment in mental health in times of crisis and global pandemic and what needs to be catered to in the near future.

Studies suggest that ATP-binding cassette transporter A1 ( ABCA1 C69T) polymorphism is associated with a decreased incidence of type 2 diabetes mellitus (T2DM) and that there is an association between ABCA1 C69T polymorphism and the risk of dyslipidemia in diabetic individuals. However, other studies contradict these suggestions. Therefore, we aimed to investigate the prevalence of ABCA1 C69T (rs1800977) gene polymorphism in a representative sample of the Saudi population not previously diagnosed with diabetes and its possible association with dyslipidemia and dysglycemia. A cross-sectional design was used to recruit nondiabetic adults of both genders from the Saudi population in Jeddah by employing a stratified, two-stage cluster sampling method. A total of 650 people (337 men and 313 women) were recruited. Demographic, dietary, and lifestyle variables, as well as medical history and family history of chronic diseases, were collected using a predesigned questionnaire. Fasting blood samples were taken for the determination of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and lipids profile, which were followed by a 1-h oral glucose tolerance test (OGTT). Real-time PCR technology was used to determine the ABCA1 C69T gene SNP (rs1800977). The T allele of ABCA1 C69T (rs1800977) was very frequent (TT in 44.9% and CT in 43.7%). There was a trend toward significance for a higher dysglycemia percentage in people with CT and TT genotypes (25.7%, and 23.3%, respectively) compared with CC genotypes (16.2%). In addition, FPG and 1-h plasma glucose were significantly higher in people with both TT and CT genotypes compared to CC genotypes. However, T allele was not associated with any dysregulation of lipid parameters.

Objective: A maternal sepsis management bundle for resource-limited settings was developed through a synthesis of evidence and international consensus. This bundle, called 'FAST-M' consists of: Fluids, Antibiotics, Source control, assessment of the need to Transport/Transfer to a higher level of care and ongoing Monitoring (of the mother and neonate). The study aimed to adapt the FAST-M intervention including the bundle care tools for early identification and management of maternal sepsis in a low-resource setting of Pakistan and identify potential facilitators and barriers to its implementation., Setting: The study was conducted at the Liaquat University of Medical and Health Sciences, which is a tertiary referral public sector hospital in Hyderabad., Design and Participants: A qualitative exploratory study comprising key informant interviews and a focus group discussion was conducted with healthcare providers (HCPs) working in the study setting between November 2020 and January 2021, to ascertain the potential facilitators and barriers to the implementation of the FAST-M intervention. Interview guides were developed using the five domains of the Consolidated Framework for Implementation Research: intervention characteristics, outer setting, inner setting, characteristics of the individuals and process of implementation., Results: Four overarching themes were identified, the hindering factors for implementation of the FAST-M intervention were: (1) Challenges in existing system such as a shortage of resources and lack of quality assurance; and (2) Clinical practice variation that includes lack of sepsis guidelines and documentation; the facilitating factors identified were: (3) HCPs' perceptions about the FAST-M intervention and their positive views about its execution and (4) Development of HCPs readiness for FAST-M implementation that aided in identifying solutions to potential hindering factors at their clinical setting., Conclusion: The study has identified potential gaps and probable solutions to the implementation of the FAST-M intervention, with modifications for adaptation in the local context TRIAL REGISTRATION NUMBER: ISRCTN17105658., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Maternal sepsis is a life-threatening condition, defined by organ dysfunction caused by infection during pregnancy, childbirth, and the postpartum period. It is estimated to account for between one-tenth and half (4.7% to 13.7%) of all maternal deaths globally. An international stakeholder group, including the World Health Organization, developed a maternal sepsis management bundle called "FAST-M" for resource-limited settings through a synthesis of evidence and international consensus. The FAST-M treatment bundle consists of five components: Fluids, Antibiotics, Source identification and control, assessment of the need to Transport or Transfer to a higher level of care and ongoing Monitoring (of the mother and neonate). This study aims to adapt the FAST-M intervention and evaluate its feasibility in Pakistan., Methods: The proposed study is a mixed method, with a before and after design. The study will be conducted in two phases at the Liaquat University of Medical and Health Sciences, Hyderabad. In the first phase (formative assessment), we will adapt the bundle care tools for the local context and assess in what circumstances different components of the intervention are likely to be effective, by conducting interviews and a focus group discussion. Qualitative data will be analyzed considering a framework method approach using NVivo version 10 (QSR International, Pty Ltd.) software. The qualitative results will guide the adaptation of FAST-M intervention in local context. In the second phase, we will evaluate the feasibility of the FAST-M intervention. Quantitative analyses will be done to assess numerous outcomes: process, organizational, clinical, structural, and adverse events with quantitative comparisons made before and after implementation of the bundle. Qualitative analysis will be done to evaluate the outcomes of intervention by conducting FGDs with HCPs involved during the implementation process. This will provide an understanding and validation of quantitative findings., Discussion: The utilization of care bundles can facilitate recognition and timely management of maternal sepsis. There is a need to adapt, integrate, and optimize a bundled care approach in low-resource settings in Pakistan to minimize the burden of maternal morbidities and mortalities due to sepsis., (© 2022. The Author(s).)

Heavy metal (HM) contamination in the drinking water is a serious threat to the consumers and has drawn the global attention. In the current study, twenty six (26) groundwater samples including tube well and domestic bores were collected randomly from fourteen union councils (UCs) of tehsil Swabi. Depth of the tube wells ranged between 100 and 400 feet, while in domestic bore water, it ranged from 22 to 140 feet. Samples were analyzed for different parameters. Concentrations of the heavy metals (HMs) were found in the following increasing orders of Pb > Zn > Cr > Cu > Ni > Cd > Co in domestic well water while in tube well water, the increasing order was Cu > Ni > Co > Zn > Cr > Cd. In the domestic well samples, Cd, Cr, Ni, and Pb were found above the World health organization (WHO), permissible limits. Based on the Water Quality Index (WQI), samples collected from domestic wells were found of poor quality with WQI value of 208, while tube well waters were found of excellent quality, with WQI value of 40. This indicates that domestic well waters are more prone to HM contamination due to low depth. Health risk data showed significantly high risk (HQ > 1) for children upon domestic well water consumption, due to high concentrations of Cr and Pb. No significance relationship was observed between the various parameters which indicate the input of these contaminants from multiple sources., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The oral polio vaccine (OPV) has substantial results in eliminating wild poliovirus and the vaccine of choice in polio eradication. However, the mucosal immunity induced by the OPV is still uncertain. Literature has shown that bovine lactoferrin (BLF) is a safe and useful protein found in cow's milk with extraordinary antimicrobial, antiviral, antiinflammatory and immune-modulatory functions that help children's gut to fight against micro-organisms like poliovirus. However, limited data exist regarding the effect of BLF on polio vaccine immune response. The primary objective is to evaluate the effect of BLF in enhancing mucosal and humoral immunity in children following the administration of oral and inactivated polio vaccines., Methods and Analysis: This is a two-arm double-blinded randomised controlled trial comparing 462 neonates (231 in both groups) receiving either BLF or placebo with breast milk. The intervention is administered from day 1 till 6 weeks of age to a full-term healthy singleton newborn born at the Aga Khan University Hospitals, Karachi, Pakistan. The primary outcome is the seroconversion, 1 month after the receipt of two doses of OPV (at 10 weeks). For descriptive statistical analysis, Stata will be used, the frequency with percentages will be reported to describe baseline characteristics of the participants. A χ 2 test will be used to compare categorical variables and a simple t test to compare continuous variables. The proportion of seroconversion and shedding will be compared using χ 2 test or Fisher's exact test., Ethics and Dissemination: The Ethics approval has been granted by the Ethics Review Committee (ERC) of Aga Khan University for the proposed trial (ID: 2019-1955-5013). Furthermore, the National Bioethics Committee (NBC) of Pakistan has also approved the study for human subject research (ID: 4-87/NBC-443/19/669). Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal., Trial Registration Number: NCT04432935; ClinicalTrials.gov., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Obstetric triage has become one of the most crucial innovations in the field of perinatal care in the past 15 years. In lower- middle- income countries (LMICs), the pregnant patients are seen in a conventional way based on the time of their arrival; this divergent, unbalanced and inequitable approach results in delayed initial evaluation, prolonged length of stay (LOS) and affected clinical outcomes.This project aimed at implementing an effective and efficient obstetric triage system with improved throughput and care processes within six months to facilitate timely decision making according to the individualized needs of pregnant patients.A pre-implementation audit was completed for the core evaluation of existing obstetric triage services, followed by a fishbone analysis. Following the Donabedian model for quality care, a quality improvement project was initiated to redesign the obstetric triage system. The project strategy was implemented as part of six PDSA (Plan- Do -Study- Act) cycles to optimize the structure, processes, and obstetric triage outcomes. The triage paradigm moved from time-based care delivery to priority care, and processes were improved based on Angelini's recommendations of best practices in obstetric triage. During the initial phase of improvement, the identified outcome measures were waiting time of 5 minutes from arrival to initial assessment, LOS of 120 minutes, and acuity-based care for at least 50% of patients. A post-implementation audit was conducted to assess improvements. The results showed that the LOS at triage reduced from 240 min (4 hours) to 60 min (1 hour) within 6 months. Furthermore, wait times for triage decreased significantly to 5 min in 65% of patients, compared with 6% in traditional triage practice.The results indicate that the traditional triage model of the 'order of arrival' process is inefficient in providing adequate obstetric care. This quality initiative facilitated the successful incorporation of the Donabedian model and best practice triage practices and helped achieve desired outcomes of improved LOS and reduced waiting time with acuity-based care. Therefore, the design of an efficient,and the appropriate obstetric triage system can be adopted by other healthcare institutions in a local setting that can facilitate patient centric care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the association of Factor V Leiden / prothrombin gene mutation in Pakistani women with adverse pregnancy outcomes., Method: The prospective study was conducted at the Aga Khan University Hospital, Karachi, from January 1 to December 31, 2016, and comprised females > 40 years having history of two or more foetal losses with no apparent aetiology. Restriction fragment length polymorphism- Polymerase chain reaction was performed using MnlI and HindIII restriction enzymes for factor V Leiden G1691A and prothrombin gene mutation G20210A. Females with two or more consecutive normal pregnancies were enrolled as the control group. Data was analysed using SPSS 19., Results: Of the 172 participants with a mean age of 29.3±5.9 years (range: 19-38 years). 86(50%) each were healthy controls and those with recurrent pregnancy loss. There were 238 livebirths among the controls compared to 13 in the other group. Factor V Leiden G1691A was identified in 2(2.3%) women, and prothrombin gene mutation G20210A in 1(1.2%) woman in the patient group, while no mutation was identified in the control group., Conclusions: The prevalence of Factor V Leiden / prothrombin gene mutation in women with recurrent pregnancy loss was found to be very low.

Objectives: To assess the overall survival of pregnant women diagnosed with cancer during pregnancy or became pregnant thereafter., Methods: A retrospective medical record review of 90 patients who were diagnosed with cancer when pregnant or who became pregnant thereafter between 1996 and 2015 in Aga Khan University Hospital, Karachi., Results: A total of 90 patients were analyzed. The malignancies that expectant mothers had were, breast cancer 38 (42.2%), hematological cancers 29 (32.2%), brain cancer 10 (11.1%), and other malignancies 13 (14.4%) that included thyroid cancers, gestational trophoblastic disease and synovial tumor of foot. We observed only four deaths out of 90 patients and mean survival time in pregnant patients with malignancies was 17.98 years [CI 16.35-19.31]., Conclusions: The diagnosis of most cancer types before or during pregnancy does not influence on overall survival of patients., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

BACKGROUND: Standard of care for bleed prevention in patients with severe congenital hemophilia A is continuous prophylaxis with factor VIII (FVIII), typically administered intravenously 2-3 times per week in the home setting. Nonfactor prophylaxis and gene therapy are emerging novel prophylaxis strategies for hemophilia A, and it is important to compare their health economics with that of FVIII prophylaxis. Current data on resource utilization and costs in the adult hemophilia A prophylaxis population are limited, and a structured approach to analyze annual costs in these patients using administrative claims data has not been previously reported. OBJECTIVE: To assess health care resource utilization and costs of continuous FVIII prophylaxis in commercially insured adults with hemophilia A without inhibitors. METHODS: Administrative claims records from beneficiaries covered by major selfinsured companies in the United States from January 1999 through March 2017 (OptumHealth Care Solutions) were queried, and records for adult patients (aged 18-64 years) diagnosed with hemophilia A who received FVIII were extracted. Three criteria were defined to distinguish patients most likely to be managed with continuous FVIII prophylaxis from those on episodic treatment based on the frequency and timing of FVIII claims over a 12-month period of continuous enrollment: (1) having ≥ 4 FVIII claims, (2) having ≥ 6 FVIII claims, or (3) having no gaps > 60 days between FVIII claims. Patients with evidence of bypassing agent use were excluded. Health care resource utilization and costs were assessed for all patients with any FVIII use and for patients defined as being managed with continuous FVIII prophylaxis based on each criterion. RESULTS: The analysis included 189 patients with a diagnosis code for hemophilia A (ICD 9-CM code 286.0; ICD-10-CM code D66) from January 1999 through March 2017 who had at least 12 months of continuous enrollment and at least 1 noninpatient/nonemergency department claim for FVIII concentrate (any type) during their last 12 months of continuous enrollment (overall cohort). Within the overall cohort, 118, 94, and 61 patients met the criteria for FVIII prophylaxis based on the first, second, and third definitions, respectively. Per patient mean (SD) total health care costs for the overall cohort was $287,055 (306,933). For patients meeting criteria 1 through 3, per patient costs ranged from $407,752 (321,036) to $551,645 (302,841). FVIII concentrate accounted for over 90% of costs, with mean (SD) annual FVIII costs of $264,777 (292,423) in the overall cohort and $384,197 (303,826), $433,029 (313,711), and $531,098 (297,142) among patients meeting the respective definitions for prophylaxis. CONCLUSIONS: This analysis highlights the substantial economic burden associated with managing adults with hemophilia A on FVIII prophylaxis, where per patient mean total annual health care costs ranged from $407,752 to $551,645. Over 90% of such costs were attributable to FVIII concentrate dispensed. DISCLOSURES: This study was funded by BioMarin Pharmaceutical, which was involved in protocol development, analysis plan development, data interpretation, manuscript preparation, and publication decisions. All authors contributed to protocol development, analysis plan development, data interpretation, and manuscript development. All authors maintained control over the final content. Sammon, Solari, Kim, and Hinds are employees and shareholders of BioMarin Pharmaceutical. Cook, Sheikh, and Chawla are employees of Analysis Group, a consulting company that was contracted by BioMarin Pharmaceutical to conduct this study and develop the manuscript. Croteau has received professional fees from BioMarin Pharmaceutical, Bayer, CSL Behring, Genentech, and Pfizer. Thornberg has received professional fees from BioMarin Pharmaceutical, Genentech, Novo Nordisk, Sanofi, and Spark Therapeutics, as well as research funding from Novo Nordisk and Sanofi.

Background: Laparoscopic sleeve gastrectomy (LSG) is the most common bariatric surgical procedure worldwide. Educational videos of LSGs are available from online sources with YouTube® being the most popular online video repository. However, due to the unrestricted and uncontrolled nature of YouTube®, anyone can upload videos without peer review or standardization. The LAP-VEGaS guidelines were formed to guide the production of high-quality surgical videos. The aim of this study is to use the LAP-VEGaS guidelines to determine if videos of LSGs available on Youtube® are of an acceptable standard for surgical educational purposes., Methods: A YouTube® search was performed using the term laparoscopic sleeve gastrectomy. Appropriate videos were analysed by two individuals using the sixteen LAP-VEGaS guidelines., Results: A total of 575 videos were found, of which 202 videos were included and analysed using the LAP-VEGaS guidelines. The median video guideline score was 6/16 with 89% of videos meeting less than half of all guidelines. There was no correlation between the LAP-VEGaS score and view count., Conclusions: There is an abundance of laparoscopic sleeve gastrectomy educational videos available on YouTube®; however, when analysed using the LAP-VEGaS guidelines, the majority do not meet acceptable educational standards for surgical training purposes.

Background: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain., Methods: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale., Results: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P = 0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P = 0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events., Conclusions: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization; Australian and New Zealand Clinical Trials Registry number, ACTRN12617000476336; Clinical Trials Registry-India number, CTRI/2017/04/008326.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Hypothyroidism in pregnancy is an arena of ongoing research, with international conflicts regarding screening, management, and outcomes. Various studies have described the outcomes depending on geographical and international diagnostic criteria. No study has been conducted in this regard from the region of Pakistan. Therefore, we aim to report the clinical features and maternal outcomes of hypothyroid pregnancies and compare the maternal outcomes between uncontrolled and controlled TSH levels in the preconception as well as the gestational period., Methods: We conducted a cross-sectional retrospective study on 718 cases in the Aga Khan University Hospital after ethical approval. We collected information on pregnant females who have diagnosed hypothyroidism before conception or during their antenatal period. We noted the maternal characteristics and maternal comorbidities. Laboratory data were recorded for thyroid stimulating hormone levels before conception and during gestation. We recorded maternal outcomes as pregnancy loss (including miscarriage, stillbirth/intrauterine death, medical termination of pregnancy and ectopic pregnancy), gestational hypertension, pre-eclampsia, postpartum hemorrhage, placental abruption, and modalities of delivery. Data analysis was performed on Statistical Package for the Social Sciences version 20.0., Results: Among 708 hypothyroid women 638 had live births. Postpartum hemorrhage was the most frequent maternal outcome (38.8%). The emergency cesarean section occurred in 23.4% of cases. We determined TSH levels in 53.2, 56.7, 61.7 and 66.6% of cases in preconception, 1st, 2nd, and 3rd trimester periods. A significant association existed between cesarean section and preconception thyrotropin levels > 2.5 mIU/L, whereas postpartum hemorrhage was significantly associated with thyrotropin levels > 2.5 mIU/L in the preconception and third trimester., Conclusion: Successful live births in our patients were complicated by maternal postpartum hemorrhage and a frequent number of emergency cesarean section.

Background: Between 2016 and 2018, San Diego County experienced a hepatitis A outbreak with a historically high mortality rate (3.4%) that highlighted the need for early recognition of those at risk of developing acute liver failure (ALF)., Methods: A retrospective case series of adult hospitalized patients with acute hepatitis A., Results: One hundred six patients with hepatitis A were studied, of whom 11 (10.4%) developed ALF, of whom 7 (6.6%) died. A history of alcohol abuse, hyperbilirubinemia, hypoalbuminemia, hyponatremia, and anemia were associated with increased odds of developing ALF. Initial Maddrey's and Model of End-Stage Liver Disease Sodium (MELD-Na) scores were also associated with the development of ALF. Multivariable analysis showed that a higher initial MELD-Na score (odds ratio [OR], 1.205; 95% confidence interval [CI], 1.018-1.427) and a lower initial serum albumin concentration (OR, 9.35; 95% CI, 1.15-76.9) were associated with increased odds of developing ALF. Combining serum albumin and MELD-Na (SAM; C-statistic, 0.8878; 95% CI, 0.756-0.988) yielded a model that was not better than either serum albumin (C-statistic, 0.852; 95% CI, 0.675-0.976) or MELD-Na (C-statistic, 0.891; 95% CI, 0.784-0.968; P = .841). Finally, positive blood cultures were more common among patients with ALF compared with those without ALF (63.6% vs 4.3%; P < .00001)., Conclusions: Hypoalbuminemia was associated with an increased risk of ALF in patients with acute hepatitis A. Positive blood cultures and septic shock as a cause of death were common among patients with ALF. Providers caring for patients with acute hepatitis A should monitor for early signs of sepsis and consider empiric antibiotics, especially in patients presenting with hypoalbuminemia., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: New Zealand has a high incidence of colorectal cancer. Most patients are treated with resectional surgery. There is a significant rate of complication associated with treatment. Costs of surgical treatment and effect of complications have not been previously investigated in New Zealand. The aim of this study was to define treatment costs of complications in patients undergoing resectional surgery for colorectal cancer., Methods: Adult patients who underwent a resectional operation for colorectal adenocarcinoma at Northland DHB between January 2011 and December 2016 were identified. Actual costs and diagnoses-related group (DRG) costs were obtained. Demographic data and information on outcomes were identified using the hospital's results reporting system CONCERTO., Results: Three hundred and ninety patients were included. One hundred and seven patients suffered a complication. Median cost per patient was $17,090. In those with complications, median cost was $28,485 compared to $14,697 in those without. Cost of complications increased as complication grade increased. Additional cost in patients with complications was on average $20,683 per patient, equating to a total of $2.2 million in this cohort., Conclusion: This study has defined the costs associated with colorectal cancer resection. Complications following colorectal surgery add significant costs. Significant investment in initiatives to reduce complications is justified., Competing Interests: Nil.

Background: The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence., Review: This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs., Conclusions: Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

Even though ion substituted hydroxyapatite nanoparticles are associated with promising features for biomedical applications, green synthesis with precise control of size and shape to produce uniform nanoparticles remains elusive. To overcome this, we herein propose a room temperature, biomimetic approach to synthesize iron substituted nano-hydroxyapatite (m-HA) along with thorough physicochemical and biological evaluation. The study revealed that 10% iron could be isomorphously doped into hydroxyapatite crystal structure. Stress, strain, energy density and atomic occupancy, as a result of substitution, have been ascertained by Williamson-Hall and Rietveld analysis using X-ray diffraction data. X-Ray photoelectron spectroscopy has been employed to confirm the elemental composition, chemical state and environment of m-HA. In addition, vibrating sample magnetometer of m-HA shows a trend towards superparamagnetic behaviour. Further, fluorescence assisted cell sorting and scanning electron microscope studies confirmed increase in the cell density with increasing iron concentration. Excellent antibacterial property, enhanced biocompatibility and bioactivity have also been interestingly observed. More controlled and sustained drug release has been observed with the inclusion of iron. A mathematical model developed to elucidate drug diffusion coefficient reveals Fickian mechanism to govern the release profile up to 8 hours followed by a non-Fickian transport. With these distinct features, this versatile material holds immense potential as bone repair material for osteoporosis where targeted delivery of calcium is required, as a heating mediator in cancer treatment and as a vehicle for site specific delivery of drug., Competing Interests: There are no conflict of interest to declare in this work., (This journal is © The Royal Society of Chemistry.)