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Background: Hyperprolactinaemia among patients on antipsychotic medications is generally overlooked due to lack of outwardly visible symptoms, patient resistance to reporting because the symptoms are perceived as shameful, or to clinician’s insufficient knowledge. Aim: The study aimed to evaluate the patterns and correlates of hyperprolactinemia among patients with schizophrenia on antipsychotic medications. Setting: The study was conducted in a psychiatric facility in Maiduguri, Northeastern Nigeria. Methods: A total of 209 patients with schizophrenia were evaluated through a cross-sectional design and assayed for serum prolactin with ELISA Kits. Frequencies and percentages were tabulated for categorical variables. Variables with significant associations with hyperprolactinaemia on chi-square (p 0.05) were subjected to logistic regression analysis. Results: The prevalence of hyperprolactinaemia was 45.9% in all patients on antipsychotic medication. The prevalence because of the use of typical and atypical antipsychotics was 51.5% and 25.0%, respectively. Hyperprolactinaemia was significantly associated with typical antipsychotics (β = 0314, p = 0.002), high overall drug dosage (β = 2.340, p = 0.003), high-dose typical antipsychotics (β = 3.228, p = 0.000), twice daily dosing frequency (β = 2.751, p = 0.001) and polypharmacy (β = 1.828, p = 0.0024). Conclusion: The findings support that patients on typical, high-dose antipsychotic medications and polypharmacy have a high prevalence of hyperprolactinaemia. As hyperprolactinaemia is often undetectable, screening and patient psycho-education on the significance of the signs and symptoms of hyperprolactinaemia is required for necessary clinical intervention. Contribution: The study provides evidence for the rational use of antipsychotic medications in sub-Saharan Africa.

Aims and Objectives: Highly active antiretroviral therapy (HAART) has been shown to reduce AIDS- defining illnesses, including neuropathies. However, it has been postulated that an increase in age -, HIV- and HAART- related neurological complications will occur as HIV-infected persons live longer. This study investigated the frequency and outcome of neuropathies in relation to CD4+ cell count and HAART status of hospitalised HIV/AIDS patients in Shika. Patients and Methods: Consecutive adult (e"15 years) non pregnant HIV- infected patients treated at Ahmadu Bello University Teaching Hospital Shika-Zaria from January 2006 to May 2013 with neuropathies were studied. Non HIV-infected patients with neurological disorders and HIV-infected patients without neuropathies were excluded. Results:Of 5240 HIV/AIDS patients seen , 11% (566) presented with neuropathy at median CD4+ cell counts of 200 cells / μl, with yearly reduction of the frequency of patients with neuropathy from 3.9% in 2006 to 0.06% in 2013. Male: female ratio was 2:1 and respective mean years were 41.9±10.1: 45.3±17.4 (p< 0.00). 253 (45%) were on HAART at presentation. 40 patients died and the mortality was associated with recurrent seizures, CD4+ cell counts d" 100 / μl, male sex, HAART-naivety and presence of co-morbidity and complications. Conclusions: The progressive reduction in the yearly frequency of neuropathy among HIV/AIDS patients suggests a beneficial effect of HAART on neuropathies. However, late presentation, low CD4+ cell counts and failure of patients to start HAART early were responsible for AIDS-related mortality thus highlighting the importance of early HIV screening and treatment.

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Introduction: The non-benzodiazepine sedative hypnotic (NBSH) eszopiclone improves polysomnography (PSG) quality and continuous positive airway pressure (CPAP) adherence. It is unclear whether zolpidem has the same effect and neither NBSH has been studied in populations with milder forms of obstructive sleep apnea.Materials and Methods: We performed a retrospective analysis on patients undergoing level I PSG at our institution. Patients are pre-medicated with NBSHs at the discretion of the sleep physician. We compared PSG/CPAP titration quality and subsequent CPAP adherence for patients receiving NBSHs or no pre-study medication. We adjusted for obstructive sleep apnea pre-test probability (PTP), arousal threshold, and other factors showing differences at baseline.Results: Data on 560 patients were analyzed. Mean age and body mass index were 42.2 ± 10.1 and 28.8 ± 4.5, respectively. Median apnea hypopnea index was 12.9 (6.4-25.3), 100 (18.0%) patients had normal studies, 97 (17.3%) were split, and 457 (81.6%) had a respiratory low-arousal threshold. After adjusting for differences at baseline, neither NBSH was associated with sleep efficiency, wake after sleep onset, or total sleep time on PSG. After adjustment, patients receiving eszopiclone had a higher apnea hypopnea index at the final CPAP pressure (β = 14.2; 95% confidence intervals (CI) 7.2-21.2; p < 0.001) and were more likely to have an unacceptable titration (odds ratio (OR) = 6.6; 95% CI 2.0-21.0; p = 0.002). When only split-night studies were examined, there were no differences in any adherence variables across or between categories.Conclusions: In a population with predominantly mild obstructive sleep apnea, NBSHs did not improve PSG or CPAP titration quality and did not increase CPAP adherence. There was no difference in effect between eszopiclone and zolpidem. [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.)

Introduction and Importance: Superior mesenteric artery (SMA) syndrome is a rare morbid vascular disorder that is defined as the decrease in the aortomesenteric angle and the compression of the third part of the duodenum. This disorder mainly affects young adult females, and severe weight loss represents a leading predisposing factor., Case Presentation: The authors report the case of a 19-year-old male who was admitted to our hospital with a 3-month history of epigastric pain, nausea, and weight loss. Two months earlier, the patient was diagnosed with Helicobacter pylori -induced gastritis. Nevertheless, with complaints of severe headache and epigastric pain, the patient was admitted to our hospital for further investigations. Computed tomography (CT) scan with intravenous contrast injection was performed, and interestingly, the aortomesenteric angle was 19° accompanied by a compression of the third part of the duodenum, and a mild gastric dilatation. Accordingly, the diagnosis was confirmed as superior mesenteric artery syndrome., Clinical Discussion: In the authors' case, the non-specific clinical symptoms correlated with histopathological examinations led to the initial diagnosis of Helicobacter pylori -induced gastritis. Surprisingly, the lack of improvements led to performing CT scan, which confirmed the diagnosis of SMA syndrome. Subsequently, HP gastritis played a significant role in misleading and delaying the diagnosis., Conclusion: The authors report the first case report from Syria of s superior mesenteric artery syndrome that was misdiagnosed and preceded by HP-induced gastritis, highlighting the crucial role of detailed clinical and radiological examinations in the diagnosis of challenging cases with morbid complications., Competing Interests: The authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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.)

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% of the patients in the intervention group, as compared with 4.3% 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.)., (Copyright © 2023 Massachusetts Medical Society.)

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.

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.

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.)

Background: The preferred timing of umbilical-cord clamping in preterm infants is unclear., Methods: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births., Results: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities., Conclusions: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).

For the first time, the heat dried biomass of a newly isolated fungus Arthrinium malaysianum was studied for the toxic Cr(VI) adsorption, involving more than one mechanism like physisorption, chemisorption, oxidation-reduction and chelation. The process was best explained by the pseudo-second order kinetic model and Redlich-Peterson isotherm with maximum predicted biosorption capacity (Q m ) of 100.69 mg g -1 . Film-diffusion was the rate-controlling step and the adsorption was spontaneous, endothermic and entropy-driven. The mode of interactions between Cr(VI) ions and fungal biomass were investigated by several methods [Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD) and Energy-Dispersive X-ray spectroscopy (EDX)]. X-ray Photoelectron Spectroscopy (XPS) studies confirmed significant reduction of Cr(VI) into non-toxic Cr(III) species. Further, a modified methodology of Atomic Force Microscopy was successfully attempted to visualize the mycelial ultra-structure change after chromium adsorption. The influence of pH, biomass dose and contact time on Cr(VI) depletion were evaluated by Response Surface Model (RSM). FESEM-EDX analysis also exhibited arsenic (As) and lead (Pb) peaks on fungus surface upon treating with synthetic solutions of NaAsO 2 and Pb(NO 3 ) 2 respectively. Additionally, the biomass could also remove chromium from industrial effluents, suggesting the fungal biomass as a promising adsorbent for toxic metals removal.

Background: Bariatric surgery is well established as an effective method for treating obesity and its related comorbidities. The laparoscopic mini-gastric bypass (MGBP) represents a simpler alternative to a Roux-en-Y gastric bypass (RYGBP). The placement of a silastic ring (SR) may enhance excess weight loss and minimize weight regain. This study reports long-term results from a cohort of patients undergoing a SR-MGBP in a single centre., Methods: Long-term outcomes (up to 11 years) in a cohort of 156 patients undergoing surgery between August 2005 and January 2008 were analysed. A combination of follow-up questionnaires and electronic hospital records were used to assess weight loss, comorbidity resolution and complications., Results: A total of 156 patients (mean body mass index 46 kg/m 2 ) underwent surgery. Ninety-two patients responded to the follow-up questionnaires. Computer-based hospital information was available on a total of 139 patients. Mean percent excess weight loss (%EWL) at 11 years was 84.3%. Comorbidity resolution, determined by medication use, showed a reduction in diabetes (21.8% to 7.1%), hypertension (37.2% to 21.4%) and hypercholesterolaemia (40.4% to 13.4%). Five of 139 patients (3.6%) had SR problems needing removal. Two other patients had the SR changed to a bigger size and a further two had endoscopic removal of the SR for erosion. Of the 139 patients, 9.4% required conversion to a Roux-en-Y gastric bypass (RYGBP). The number of patients on anti-reflux medications increased from 5.1% to 44.6% at 11 years. There were two deaths unrelated to surgery., Conclusions: SR-MGBP appears to be a safe and effective operation for the morbidly obese. It is durable, with good weight loss at up to 11 years post-surgery. The SR can easily be removed or exchanged for another size and is reasonable to consider when performing a MGBP. Concerns about bile reflux appear to be well founded, and some patients who are poorly controlled medically will require revision.

Background: Clinical prediction rules (CPRs) provide an objective method of assessment in the diagnosis of acute appendicitis. There are a number of available CPRs for the diagnosis of appendicitis, but it is unknown which performs best., Aim: The aim of this study was to identify what CPRs are available and how they perform when diagnosing appendicitis in adults., Method: A systematic review was performed in accordance with the PRISMA guidelines. Studies that derived or validated a CPR were included. Their performance was assessed on sensitivity, specificity and area under curve (AUC) values., Results: Thirty-four articles were included in this review. Of these 12 derived a CPR and 22 validated these CPRs. A narrative analysis was performed as meta-analysis was precluded due to study heterogeneity and quality of included studies. The results from validation studies showed that the overall best performer in terms of sensitivity (92%), specificity (63%) and AUC values (0.84-0.97) was the AIR score but only a limited number of studies investigated at this score. Although the Alvarado and Modified Alvarado scores were the most commonly validated, results from these studies were variable. The Alvarado score outperformed the modified Alvarado score in terms of sensitivity, specificity and AUC values., Conclusion: There are 12 CPRs available for diagnosis of appendicitis in adults. The AIR score appeared to be the best performer and most pragmatic CPR.

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 sp 2 /sp 3 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., Competing Interests: Disclosure The authors declare no conflicts of interest in this work.

Background: There are indications that teachers have limited knowledge about attention deficit hyperactivity disorder (ADHD), despite its high prevalence in childhood and its long-term effects on students such as academic underachievement, reduced self-esteem, and social and behavioural difficulties. This study is therefore aimed at assessing the effect of an ADHD training program on the knowledge of ADHD among primary school teachers in Kaduna, Nigeria and their attitudes towards pupils with ADHD., Methods: This was a randomized controlled trial involving 84 primary school teachers in the intervention group and 75 teachers in the control group. Participants in the intervention group received an initial 3-h training with a one-and-a-half hour booster session 2 weeks later using the World Health Organisation MhGAP-IG module on behavioural disorders focusing on ADHD. Outcome measures were knowledge of ADHD, attitude towards ADHD, and knowledge of behavioural intervention., Results: Controlling for baseline scores, the intervention group had significantly higher post intervention scores on knowledge of ADHD, lower scores on attitude towards ADHD (i.e. less negative attitudes), and higher scores on knowledge of behavioural intervention compared with the control group respectively. The intervention showed moderate to large effect sizes. The booster training was associated with a further statistically significant increase in knowledge of ADHD only., Conclusions: The training program significantly improved the knowledge and attitudes of the teachers in the intervention group towards ADHD. Considerations should be given to incorporating ADHD training programs into teacher-training curricula in Nigeria, with regular reinforcement through in-service training.

Background: The National Institutes of Health Stroke Scale (NIHSS) was designed primarily as a research instrument and is used in clinical settings. Its use has not yet been examined as a predictor of patient functional outcomes and prognosis in a community hospital setting., Objectives: The aim of this study was to determine the effectiveness of baseline NIHSS score in predicting patient functionality and disposition at discharge in a designated stroke center at a community hospital., Methods: The study population included every transient ischemic attack and stroke encounter seen at our community hospital over the past 6 years (n = 2909). Neurological impairment at baseline was quantified using the NIHSS score on the patient's arrival. Outcomes included the patient's discharge disposition (expired or alive) and ambulatory status at discharge. Results were adjusted for age, gender, race, and stroke, myocardial infarction, diabetes, and hypertension history. Analysis was done using R-based statistical tools., Results: Baseline NIHSS score was a strong predictor of both patient discharge disposition and ambulatory status. After adjusting for confounding factors, with every 1 point increase in the stroke scale at baseline, there was a 2.3 times increased likelihood of mortality and 3 times increased likelihood in worsening of ambulatory function., Conclusions: In our community hospital setting, the NIHSS score was found to be a strong predictor of patient recovery after stroke. The NIHSS score at baseline may be important for clinicians to consider before patient management decisions and counseling.

This paper describes a simple method for the room temperature synthesis of magnetite/hydroxyapatite composite nanocomposites using ferrofluids. The in situ synthesis of magnetic-hydroxyapatite results in a homogenous distribution of the two phases as seen both in transmission electron micrographs and assembled to a micron range in the confocal micrographs. The selected area diffraction pattern analysis shows the presence of both phases of iron oxide and hydroxyapatite. To the dialyzed ferrofluid, the constituents of hydroxyapatite synthesis was added, the presence of the superparamagnetic iron oxide particles imparts directionality to the hydroxyapatite crystal growth. Electron probe microanalysis confirms the co-existence of both iron and calcium atoms. Vibrating Sample magnetometer data shows magnetization three times more than the parent ferrofluid, the local concentration of iron oxide nanoparticles affects the strength of dipolar interparticle interactions changing the energy barrier for determining the collective magnetic behavior of the sample. The limitations inherent to the use of external magnetic fields which can be circumvented by the introduction of internal magnets located in the proximity of the target by a minimal surgery or by using a superparamagnetic scaffold under the influence of externally applied magnetic field inspires us to increase the magnetization of our samples. The composite in addition shows anti-bacterial properties against the two gram (-ve) bacteria tested. This work is significant as magnetite-hydroxyapatite composites are attracting a lot of attention as adsorbents, catalysts, hyperthermia agents and even as regenerative medicine.

Controlled size, shape and dispersibility of superparamagnetic iron oxide nanoparticles (SPIONs), has been achieved in a protein-polymer colloidal dispersion. Stable ferrofluid (FF) is synthesized in an aqueous medium of collagen, bovine serum albumin and poly(vinyl) alcohol that equilibrates with time, at ambient conditions, into an organized matrix with iron oxide particles sterically caged at defined sites. It mimics a biomineralization system; hence the process is termed biomimetics. Though the exact mechanism is not understood at this stage, we have established, with serial dilution of the protein-polymer solution that the SPIONs are formed inside the self-contained clusters of the two proteins and the polymer, which show a tendency to self assemble. More than the interparticle dipolar attractions of magnetic particles, electrostatic interactions play a role in cluster formation and collagen is responsible for the overall stability, supported by systematic dynamic light scattering data. The basic aim of this study was to increase magnetization of a previously synthesized ferrofluid without hampering stability, by reducing the total macromolecular concentration. Thrice the magnetization was achieved and in addition, the synthesized FFs exhibited very high transverse relaxivity and showed good contrast in mice liver, in the in vivo studies.

Background: Symptomatic osteoarthritis poses a major challenge to primary health care but no studies have related accessing primary care ('detection'), receiving recommended treatments ('treatment'), and achieving adequate control ('control')., Objective: To provide estimates of detection, treatment, and control within a single population adapting the approach used to determine a Rule of Halves for other long-term conditions., Setting: General population., Participants: 400 adults aged 50+ years with prevalent symptomatic knee osteoarthritis., Design: Prospective cohort with baseline questionnaire, clinical assessment, and plain radiographs, and questionnaire follow-up at 18 and 36 months and linkage to primary care medical records., Outcome Measures: 'Detection' was defined as at least one musculoskeletal knee-related GP consultation between baseline and 36 months. 'Treatment' was self-reported use of at least one recommended treatment or physiotherapy/hospital specialist referral for their knee problem at all three measurement points. Pain was 'controlled' if characteristic pain intensity <5 out of 10 on at least two occasions., Results: In 221 cases (55.3%; 95%CI: 50.4, 60.1) there was evidence that the current problem had been detected in general practice. Of those detected, 164 (74.2% (68.4, 80.0)) were receiving one or more of the recommended treatments at all three measurement points. Of those detected and treated, 45 (27.4% (20.5, 34.3)) had symptoms under control on at least two occasions. Using narrower definitions resulted in substantially lower estimates., Conclusion: Osteoarthritis care does not conform to a Rule of Halves. Symptom control is low among those accessing health care and receiving treatment., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

In the present study, an in vitro blood–brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood–brain barrier model was completed by examining the permeability of FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood–brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood–brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood–brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood–brain barrier (e.g. CPB).

Background: Wilson's disease is a rare, autosomal recessive inherited disorder characterized by impaired liver metabolism of copper leading to decreased biliary excretion and incorporation of ceruloplasmin levels mainly in the liver and brain. Untreated Wilson's disease has been shown to cause subfertility and even in cases where pregnancy occurs, it often results in spontaneous miscarriage., Case Presentations: We present four cases of successful pregnancy outcomes in three patients diagnosed with Wilson's disease along with the literature review. All the patients were managed with zinc sulphate without any postnatal complications., Conclusion: Patients with Wilson's disease receiving regular treatment who remain asymptomatic are usually able to conceive and achieve successful outcomes. However, these pregnancies should be considered high risk and merit regular surveillance.

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.

Background: Gene expression profiles of several tumor suppressor genes are regulated by the methylation and demethylation of their promoters. Here, we aim to identify and quantify the methylation status of four tumor suppressor genes from placentas at term and compare them with the maternal white-blood-cells., Methods: In order to achieve this objective, DNA enriched from twenty placentas at term and maternal white blood cells was bisulfite-converted and amplified using quantitative real-time methyl-light polymerase chain reaction for the four-genes studied (RASSF1A, APC, RAR-beta, and PTGS2)., Results: Among the four genes examined, RASSF1A, APC and RAR-beta promoter regions were hypermethylated in all the placental samples compared with maternal WBCs. Strikingly, PTGS2 was found to be hypomethylated in the placentas compared to the maternal cells., Conclusion: Since placental DNA represents fetal methylation profile and it is an established fact that there is certain amount of cell free circulating DNA in human plasma/serum, these data strongly suggest that hypermethylation of RASSF1A, APC and RAR-beta can be used as gender independent biomarkers to distinctly identify placental DNA in maternal blood. In addition, this is the first report which demonstrates hypomethylation of PTGS2 locus which may have important clinical implications e.g. placental abnormalities.

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.

Objective: To assess the factors associated with failed induction of labour (IOL) in a secondary care hospital., Method: This is a retrospective cross sectional study on women admitted for labour induction in Aga Khan Hospital for women Karimabad from 1st Jan, 2009 to 31st Dec, 2009. Induction was considered successful if the patient delivered vaginally and failed if it ended up in Caesarean Section., Result: Eighteen percent of our pregnant population who underwent induction of labour failed to deliver vaginally. About 25% of 328 nulliparous women had failed induction. With a Bishop score of <5 in 84.3%. In 28.2% with prolonged latent phase of more than 20 hours in Caesarean section had to be performed., Conclusion: Nulliparity, poor Bishop score and prolonged latent phase had strongest association with failed Induction of Labour. Macrosomia, gestation age, bad obstetric history and pre labour rupture of membranes were other significant risk factors for emergency caesarean sections in IOL.