National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Future of mental health in the metaverse

The metaverse and non-fungible tokens(NFTs)were some of the hottest tech terms in 2021,according to a Google Trends search.Our review aims to describe the metaverse and NFTs in the context of their potential application in the treatment of mental health disorders.Advancements in technology have been changing human lives at an ever-increasing pace.Metaverse,also known as the threedimensional(3D)internet,is the convergence of virtual reality(VR)and physical reality in a digital space.It could potentially change the internet as we know it,with NFTs as the key building blocks in the new expansive virtual ecosystem.This immersive 3D virtual world boasts the features of the real world with the added ability to change the surrounding environment according to individual needs and requirements.VR,augmented reality(AR)and mixed reality(MR)have been employed as tools in the treatment of various mental health disorders for the past decade.Studies have reported positive results on their effectiveness in the diagnosis and treatment of mental health disorders.VR/AR/MR have been hailed as a solution to the acute shortage of mental health professionals and the lack of access to mental healthcare.But,on the flip side,young adults tend to spend a significant amount of time playing 3D immersive games and using social media,which can lead to insecurity,anxiety,depression,and behavioural addiction.Additionally,endless scrolling through social media platforms negatively affects individuals'attention span as well as aggravating the symptoms of adolescents with attention deficit hyperactivity disorder.We aimed to explore the ramifications of expanding applications of the metaverse on mental health.So far,no other review has explored the future of mental health in the context of the metaverse.

Acceptance,availability and feasibility of RTS,S/AS01 malaria vaccine:A review of literature

Malaria remains the most serious infectious disease and is one of the leading causes of death among children in malaria endemic areas.The development of malaria vaccines has been underway since 1960s.Significant progress in the development of vaccine has been made in the last decade.On 6 October 2021,World Health Organization recommended widespread use of the RTS,S/AS01 malaria vaccine.The level of acceptance of RTS,S/AS01 malaria vaccine is relatively low in middle-income countries.This might be because of lack of information regarding vaccine implementation in such countries.The proper and efficient execution of the malaria vaccination program necessitates careful consideration of each community's socio-cultural setting.The most prominent RTS,S/AS01 vaccine trial was conducted from 2009 to 2011 in which eleven sites in seven African countries participated.Results of the trial,published in 2015,provided a promising advance in the development of a malaria vaccine for African children.As of 2019,large-scale pilot studies of the vaccine have been conducted in Ghana,Kenya,and Malawi,involving several hundreds of thousands of infants.The RTS,S/AS01 vaccine shows modest efficacy against malaria and has a feasible mode of administration.Although there is increased risk of meningitis,cerebral malaria,pneumonia,anemia,febrile convulsions and gastroenteritis,the vaccine still has a feasible mode of administration and high cost effectiveness and can be easily implemented in resource-limited settings.

Evolving paradigm of thrombolysis in pulmonary embolism:Comprehensive review of clinical manifestations,indications,recent advances and guideline

Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE,in addition to hemodynamic instability symptoms.This prevents the progression of right heart failure and impending hemodynamic collapse.Diagnosing PE can be challenging due to the variety of presentations;therefore,guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition.Traditionally,systemic thrombolysis has been utilized to lyse the emboli in PE.However,newer techniques for thrombolysis have been developed,such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediatehigh submassive risk groups.Additional newer techniques explored are the use of extracorporeal membrane oxygenation,direct aspiration,or fragmentation with aspiration.Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials,choosing the best course of treatment for a given patient may be difficult.To help,the Pulmonary Embolism Reaction Team is a multidisciplinary,rapid response team that has been developed and is used at many institutions.Hence to bridge the knowledge gap,our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.

Attitudes and understanding of complementary and alternative medicine in cancer care:An exploratory study of patients’perspectives in Karachi,Pakistan

Objective:To evaluate the prevalence and types of complementary and alternative medicine(CAM)modalities among patients with cancer in Karachi,Pakistan.Methods:This descriptive cross-sectional study was conducted from March 2021 to December 2021.Five hundred patients with cancer were invited to participate in the study.Electronic databases,namely,Google scholar,Publons,EMBASE,PubMed,Chinese National Knowledge Infrastructure Database,and ResearchGate was used for questionnaire designed.The self-administered survey included questions on demographic characteristics,education level,socio-economic conditions and information about CAM therapies,prevalence,effectiveness,and common CAM modalities.Statistical analysis was conducted using SPSS software version 22.Results:Out of the 500 invited patients,433(86.6%)successfully completed and returned the questionnaires.In contrast to patients who were with younger,highly educated,professionally active,higher income,and had advanced cancer,time since diagnosis,type of treatment,cancer types and family history are significantly associated with CAM use.The results showed that 59.8%of the participants were acquainted with complementary and/or alternative medicine and considered safe owing to its natural ingredients.The prevalence of CAM usage among cancer patients was 40.9%and the most widely used CAM modality was herbal medicine(27.7%)and dietary supplements(28.8%).Patients used CAM as a complementary therapy to improve the morphological parameter(28.2%),strengthen the immune system(6.8%),and to decrease the side effects of conventional treatment(18.1%).Most of the respondents get the information regarding CAM therapy from the electronic media(43.2%)and the family members(48%)rather than healthcare personnel.Conclusions:Participants used CAM modalities along with the conventional health care practices.Further multicentre studies should be conducted to provide information regarding the usage of CAM therapies and their eventual benefits in patients with cancer.

Sodium-glucose cotransporter-2 inhibitor-associated euglycemic diabetic ketoacidosis in COVID-19-infected patients: A systematic review of case reports

BACKGROUND Diabetic ketoacidosis(DKA)manifests as hyperglycemia,metabolic acidosis,and ketosis.However,euglycemic DKA(eu-DKA)conceals severe DKA with glucose levels below 200 mg/dL.Sodium-glucose cotransporter-2(SGLT2)inhibitors can induce eu-DKA in diabetic patients.Notably,coronavirus disease 2019(COVID-19)-infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets.This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis.Additionally,we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors,providing indispensable insights for healthcare professionals managing this specific patient population.AIM To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.METHODS We conducted an exhaustive search across prominent electronic databases,including PubMed,SCOPUS,Web of Science,and Google Scholar.This search encompassed the period from December 2019 to May 2022,incorporating published studies and pre-prints.The search terms employed encompassed“SGLT2 inhibitors”,“euglycemic DKA”,“COVID-19”,and related variations.By incorporating these diverse sources,our objective was to ensure a thorough exploration of the existing literature on this subject,thereby augmenting the validity and robustness of our findings.RESULTS Our search yielded a total of seven case reports and one case series,collectively comprising a cohort of twelve patients.These reports detailed instances of eu-DKA in individuals with COVID-19.Crucially,all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication.Upon admission,all oral medications were promptly discontinued,and the patients were initiated on intravenous insulin therapy to effectively manage the DKA.Encouragingly,eleven patients demonstrated a favorable outcome,while regrettably,one patient succumbed to the condition.Subsequently,SGLT2 were discontinued for all patients upon their discharge from the hospital.These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2,underscoring the critical importance of prompt intervention and vigilant medication adjustments.CONCLUSION Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA,as well as encountering adverse outcomes in the context of COVID-19,despite maintaining satisfactory glycemic control.The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous.Consequently,this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.

Effect of fibrinolytic therapy on ST-elevation myocardial infarction clinical outcomes during the COVID-19 pandemic:A systematic review and meta-analysis

BACKGROUND ST-elevation myocardial infarction(STEMI)is the result of transmural ischemia of the myocardium and is associated with a high mortality rate.Primary percutaneous coronary intervention(PPCI)is the recommended first-line treatment strategy for patients with STEMI.The timely delivery of PPCI became extremely challenging for STEMI patients during the coronavirus disease 2019(COVID-19)pandemic,leading to a projected steep rise in mortality.These delays were overcome by the shift from first-line therapy and the development of modern fibrinolytic-based reperfusion.It is unclear whether fibrinolytic-based reperfusion therapy is effective in improving STEMI endpoints.AIM To determine the incidence of fibrinolytic therapy during the COVID-19 pandemic and its effects on STEMI clinical outcomes.METHODS PubMed,Google Scholar,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were queried from January 2020 up to February 2022 to identify studies investigating the effect of fibrinolytic therapy on the prognostic outcome of STEMI patients during the pandemic.Primary outcomes were the incidence of fibrinolysis and the risk of all-cause mortality.Data were meta-analyzed using the random effects model to derive odds ratios(OR)and 95%confidence intervals.Quality assessment was carried out using the Newcastle-Ottawa scale.RESULTS Fourteen studies including 50136 STEMI patients(n=15142 in the pandemic arm;n=34994 in the pre-pandemic arm)were included.The mean age was 61 years;79%were male,27%had type 2 diabetes,and 47%were smokers.Compared with the pre-pandemic period,there was a significantly increased overall incidence of fibrinolysis during the pandemic period[OR:1.80(1.18 to 2.75);I2=78%;P=0.00;GRADE:Very low].The incidence of fibrinolysis was not associated with the risk of all-cause mortality in any setting.The countries with a low-and middle-income status reported a higher incidence of fibrinolysis[OR:5.16(2.18 to 12.22);I2=81%;P=0.00;GRADE:Very low]and an increased risk of all-cause mortality in STEMI patients[OR:1.16(1.03 to 1.30);I2=0%;P=0.01;GRADE:Very low].Meta-regression analysis showed a positive correlation of hyperlipidemia(P=0.001)and hypertension(P<0.001)with all-cause mortality.CONCLUSION There is an increased incidence of fibrinolysis during the pandemic period,but it has no effect on the risk of all-cause mortality.The low-and middle-income status has a significant impact on the all-cause mortality rate and the incidence of fibrinolysis.

Metabolic puzzle: Exploring liver fibrosis differences in Asian metabolic-associated fatty liver disease subtypes

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is a liver condition marked by excessive fat buildup in the absence of heavy alcohol use.It is primarily linked with metabolic issues like insulin resistance,obesity,and abnormal lipid levels,and is often observed with other conditions such as type 2 diabetes and cardiovascular disease.However,whether the subtypes of MAFLD based on the metabolic disorder differentially impact liver fibrosis is not well explicated,especially in the Asian population.AIM To compare the severity of liver fibrosis among different MAFLD subtypes.METHODS A total of 322 adult patients of either gender with fatty liver on ultrasound were enrolled between January to December 2021.MAFLD was defined as per the Asian Pacific Association for the Study of the Liver guidelines.Fibrosis-4 index(Fib-4)and nonalcoholic fatty liver disease fibrosis score(NFS)were employed to evaluate liver fibrosis.RESULTS The mean age was 44.84±11 years.Seventy-two percent of the patients were female.Two hundred and seventy-three patients were classified as having MAFLD,of which 110(40.3%)carried a single,129(47.3%)had two,and 34(12.5%)had all three metabolic conditions.The cumulative number of metabolic conditions was related to elevated body mass index,triglyceride(TG)levels,and glycated hemoglobin,lower high-density lipoprotein(HDL)levels,higher liver inflammation(by aspartate aminotransferase andγ-glutamyl transferase),and higher likelihood of fibrosis(by NFS and Fib-4 scores)(P<0.05 for all).The proportion of advanced fibrosis also increased with an increase in the number of metabolic conditions(4.1%,25.5%,35.6%,and 44.1%by NFS and 6.1%,10.9%,17%,and 26.5%by Fib-4 for no MAFLD and MAFLD with 1,2,and 3 conditions,respectively).Among MAFLD patients,those with diabetes alone were the eldest and had the highest mean value of NFS score and Fib-4 score(P<0.05),while MAFLD patients diagnosed with lean metabolic dysfunction exhibited the highest levels of TG and alanine aminotransferase but the lowest HDL levels(P<0.05).CONCLUSION The study suggests that the severity of liver fibrosis in MAFLD patients is influenced by the number and type of metabolic conditions present.Early identification and management of MAFLD,particularly in patients with multiple metabolic conditions,are crucial to prevent liver-related complications.

Left bundle branch pacing vs biventricular pacing in heart failure patients with left bundle branch block:A systematic review and meta-analysis

BACKGROUND Left bundle branch pacing(LBBP)is a novel pacing modality of cardiac resynchronization therapy(CRT)that achieves more physiologic native ventricular activation than biventricular pacing(BiVP).AIM To explore the validity of electromechanical resynchronization,clinical and echocardiographic response of LBBP-CRT.METHODS Systematic review and Meta-analysis were conducted in accordance with the standard guidelines as mentioned in detail in the methodology section.RESULTS In our analysis,the success rate of LBBP-CRT was determined to be 91.1%.LBBP CRT significantly shortened QRS duration,with significant improvement in echocardiographic parameters,including left ventricular ejection fraction,left ventricular end-diastolic diameter and left ventricular end-systolic diameter in comparison with BiVP-CRT.CONCLUSION A significant reduction in New York Heart Association class and B-type natriuretic peptide levels was also observed in the LBBP-CRT group vs BiVP-CRT group.Lastly,the LBBP-CRT cohort had a reduced pacing threshold at follow-up as compared to BiVP-CRT.

Infectious diseases in the aftermath of monsoon flooding in Pakistan

Pakistan is ranked 9th in terms of flood-affected countries worldwide.In the summer of 2010,the northern province of Khyber-Pakhtunkhwa received more than 312 mm of rain in a 56 hour period.This resulted in over 1 600 deaths across the region.In addition,over 14 million people were directly affected by this record-breaking deluge.Flood affected regions serve as ideal breeding grounds for pathogens,leading to the spread of diseases.The poor standards of hygiene in camps set up for individuals displaced by the floods also contribute to this.It is essential that those involved in relief efforts are aware of the epidemiology of diseases that have historically seen a sudden upsurge after natural disasters.Keeping this in mind,we conducted a simple review of literature.An extensive literature search was conducted using the PubMed data base and online search engines.Articles published in the last 20 years were considered along with some historical articles where a background was required.Seven major diseases were identified to increase substantially in the aftermath of natural disasters.They were then classified into acute and sub-acute settings.Diarrhea,skin&eye infections and leptospirosis were identified in the acute setting while malaria,leishmaniasis,respiratory infections and hepatitis were identified in the sub-acute setting.

New Method for Optimization and Simultaneous Determination of Sparfloxacin and Non Steroidal Anti-Inflammatory Drugs: Its <i>In-Vitro</i>Application

A simple reversed phase HPLC method was developed and validated for the simultaneous determination of sparfloxacin (SPFX), diclofenac sodium, meloxicam, ibuprofen, flurbiprofen, naproxen and mefenemic acid in a relatively short time with high linearity in bulk material, pharmaceutical formulations and human serum. Purospher STAR C18 (250 × 4.6 mm, 5 μm) column was utilized with mobile phase, methanol and water (90:10, v/v pH 2.70 adjusted by phosphoric acid), was delivered at a flow rate of 1.5 mL.min–1. Eluent was monitored using UV detector at 240 nm. The proposed method is specific, accurate (98.42% - 102.75%), precise (intra-day and inter-day variation 0.011% - 1.85%) and linear (R2 > 0.999) with in the desired range 0.15 - 40 μg.mL–1 and the detection and quantification limit was 1.19E+08 – 0.150 μg.mL–1 and 3.62E+08 – 0.4574 μg.mL–1 respectively for SPFX and NSAIDs. The analysis of variance (ANOVA) and student’s t-test were applied to verify the results. The anticipated method is applicable to routine analysis of SPFX and NSAIDs in pharmaceutical formulations as well as in human serum samples. It has also applied on interaction of SPFX with NSAIDs.

Determination of correlation of Adjusted Blood Requirement Index with outcome in patients presenting with acute variceal bleeding

AIM:To determine the correlation of Adjusted Blood Requirement Index(ABRI) with the 7th day outcome in patients presenting with acute variceal bleeding.METHODS:All patients presenting with acute variceal hemorrhage(AVH) were included.Patients with previous band ligation,sclerotherapy,gastrointestinal or hepatic malignancies were excluded.Patients were managed as per standard protocol for AVH with terlipressin and band ligation.ABRI scores were calculated using the formula outcome of alive or expired up to the 7th day after treatment.The correlation between ABRI and mortality was estimated and a receiver operative characteristic(ROC) curve was plotted.RESULTS:A total of 113 patients(76 male;37 female) were included.On assessment,18 were in Child's Pugh Class A,82 in Class B and 13 were in Class C.The median number of blood units transfused ± inter-quartile range was 3.0 ± 2.0.The median ± inter-quartile range for ABRI was 1.3 ± 1.1.The ROC curve of ABRI for expiry showed a signifi cantly large area of 0.848(P < 0.0001;95% CI:0.75-0.95) .A significant correlation of log transformation of ABRI with an outcome of mortality was present(P < 0.0001) .CONCLUSION:ABRI correlates strongly with mortality.

Divergent trajectories of lean vs obese non-alcoholic steatohepatitis patients from listing to post-transplant:A retrospective cohort study

BACKGROUND Non-alcoholic steatohepatitis(NASH)cirrhosis is the second most common indication for liver transplantation(LT).The role of body mass index(BMI)on outcomes of NASH cirrhosis has been conflicting.AIM To compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis,from listing up to post-transplant,having adjusted their BMI for ascites.METHODS We retrospectively reviewed all adult NASH patients listed for LT in our program from 2012 to 2019.Fine-Gray Competing Risk analyses and Cox Proportional-Hazard Models were performed to examine the cumulative incidence of transplant and survival outcomes respectively.RESULTS Out of 265 NASH cirrhosis listed patients,176 were included.Median age was 61.0 years;46%were females.111 patients underwent LT.Obese robust patients had better waitlist survival[hazard ratio(HR):0.12;95%CI:0.05–0.29,P<0.0001]with higher instantaneous rate of transplant(HR:5.71;95%CI:1.26–25.9,P=0.02).Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT(1.2%vs 13.8%,P=0.032)and death post-LT(2.4%vs 17.2%,P=0.029).1-3-and 5-year graft survival was poor for lean NASH(78.6%,77.3%and 41.7%vs 98.6%,96%and 85%respectively).Overall patient survival post-LT was significantly worse in lean NASH(HR:0.17;95%CI:0.03–0.86,P=0.0142)with 83%lower instantaneous rate of death in obese group.CONCLUSION Although lean NASH is considered to be more benign than obese NASH,our study suggests a paradoxical correlation of lean NASH with waitlist outcomes,and graft and patient survival post-LT.

Spectrum of Diseases, Disease Related Mortality and Overall Financial Burden of Hospitalized Patients in Medical Wards of Tertiary Care Public Hospital

Background: Detailed assessment of pattern of diseases and trend of mortalities tends to aid in formulating pivotal aspects of in-hospital policies, standards of care and so consequently promoting efficient work system. This also reserves limited resources keeping within the limit of financial grasp. The study aims to reimburse the colossal paucity of data covering epidemiological burden of diseases, impact on mortality as well as financial burden in socioeconomically challenged public health system. Methods: This was a retrospective cross-sectional hospital based study conducted in department of Medicine, Civil Hospital Karachi, from February 2016 to July 2016 using questionnaire based data collection system. Results: Eight thousand and fifty three (8053) cases with almost equal gender proportion were analyzed. Chronic liver disease (CLD) was the most rampant disease, followed by cerebrovascular accident (CVA), tuberculosis and diabetes. Overall 51% cases were attributed to infectious diseases. Overall the average percentage mortality was found to be 20% of all cases. Mean duration of stay was 7.56 ± 7 days. Estimated average total in-hospital expenditure per patient on each visit or stay was 159.15 ± 41.2 $USD (16670.96 ± 4315.7 PKR). Average total diagnostic and medications costs per visit or stay were 89.74 ± 31.2 $USD (9400.26 ± 3268.2 PKR) and 48.68 ± 18.0 $USD (5099.23 ± 1885.5 PKR) respectively. Conclusion: Chronic liver disease, cerebrovascular accident and diabetes were most frequent reasons of hospital admission and mortality. Recognition of most common and fatal diseases with their expenditure is going to lead to formulation of targeted policies both of which would be effective and efficient.

Assessment of Clinical Learning Environment, Supervision (CLES) among Nursing Students, Hyderabad, Sindh, Pakistan

Background: In nursing education for better teaching and essential professional skills, the clinical practice plays a substantial role. Practice at clinical settings permits students to convert theoretic knowledge into the knowledge of the skills mandatory for the care of the patient. Clinical learning environment (CLE) is an important part in education of nursing and has a sizable influence on the students’ learning. Objective: The purpose of this study is to examine perception and satisfaction of nursing students with their CLEs in Hyderabad, Pakistan. Methods: This cross-sectional study was conducted at three nursing institutes of Hyderabad from December 2018 to January 2019 among 342 nursing students. Clinical Learning Environment, Supervision and Nurse Teacher (CLES + T) assessment tool was used as the instrument to identify the students’ perception about the learning environment in clinical setting. Results: The mean age of the participants was 25.6 ± 4.93 with majority of them male (70.7%). Three domains, pedagogical atmosphere, supervisory relationship and nurse teacher role in clinical practice showed good reliability of more than 70%. Highest domains vise mean score was obtained for nursing premises on the ward (3.315) whereas lowest for nurse teacher role in clinical practice (NT) (3.062). Analysis of variance revealed that three domains supervisory relationship, leadership style of the ward manager and premises of nursing showed significant mean score difference among supervisor title. Conclusion: It was found that students valued positive supervision, ward manager leadership style premises of nursing on the ward as positive CLE. Learning environment varies between gender, clinical settings and supervision. Medicine ward appeared to deliver the finest learning situations for the nursing program.

Frequency of Musculoskeletal Pain and Associated Factors among Undergraduate Students

Objective: To study and compare the prevalence of musculoskeletal pain in Medical and non-medical students and find out the specific factors associated with the occurrence of this pain. Methodology: This is a cross-sectional study from March-May 2017 where a total of 400 medical and 350 non-medical students were registered using a structured questionnaire made by modification of Nordic questionnaire. Characteristics of musculoskeletal pain were determined Pain was also graded by using a grading scale. Results: Mean age for medical and non-medical students was 21.36 and 20.97 respectively. The prevalence of musculoskeletal pain was higher among females. More data were collected from 2nd and 5th year of medical and 1st and 2nd year of non-medical students. High incidence was found in medical students with occurrence mostly in Neck. This frequency of musculoskeletal pain was quiet high during the last 7 days. The long study hours and use of computer/laptop were found to be greater among medical undergraduates but no significant association was found in medical unlike non-medical students. Majority of undergraduate students reported a normal BMI. Our study has found no co-relation of BMI with prevalence of pain. It was also observed that medical students with musculoskeletal pain spent more time on travelling when compared to non-medical. Association was found with the use of back packs. The study observed the level of many daily activities like exercise and outdoor sports etc. but no significant relation was found. Conclusion: Prevalence of musculoskeletal pain among undergraduate students is truly high, more so in medical students. Medical students have shown no association of studying for long hours and use of computer/laptop with musculoskeletal pain when compared to non-medical students. More studies should be done to know contributing factors of musculoskeletal pain among undergraduate students.

Combination of mesenchymal stem cells and three-dimensional collagen scaffold preserves ventricular remodeling in rat myocardial infarction model

BACKGROUND Cardiovascular diseases are the major cause of mortality worldwide.Regeneration of the damaged myocardium remains a challenge due to mechanical constraints and limited healing ability of the adult heart tissue.Cardiac tissue engineering using biomaterial scaffolds combined with stem cells and bioactive molecules could be a highly promising approach for cardiac repair.Use of biomaterials can provide suitable microenvironment to the cells and can solve cell engraftment problems associated with cell transplantation alone.Mesenchymal stem cells(MSCs)are potential candidates in cardiac tissue engineering because of their multilineage differentiation potential and ease of isolation.Use of DNA methyl transferase inhibitor,such as zebularine,in combination with three-dimensional(3D)scaffold can promote efficient MSC differentiation into cardiac lineage,as epigenetic modifications play a fundamental role in determining cell fate and lineage specific gene expression.AIM To investigate the role of collagen scaffold and zebularine in the differentiation of rat bone marrow(BM)-MSCs and their subsequent in vivo effects.METHODS MSCs were isolated from rat BM and characterized morphologically,immunophenotypically and by multilineage differentiation potential.MSCs were seeded in collagen scaffold and treated with 3μmol/L zebularine in three different ways.Cytotoxicity analysis was done and cardiac differentiation was analyzed at the gene and protein levels.Treated and untreated MSC-seeded scaffolds were transplanted in the rat myocardial infarction(MI)model and cardiac function was assessed by echocardiography.Cell tracking was performed by DiI dye labeling,while regeneration and neovascularization were evaluated by histological and immunohistochemical analysis,respectively.RESULTS MSCs were successfully isolated and seeded in collagen scaffold.Cytotoxicity analysis revealed that zebularine was not cytotoxic in any of the treatment groups.Cardiac differentiation analysis showed more pronounced results in the type 3 treatment group which was subsequently chosen for the transplantation in the in vivo MI model.Significant improvement in cardiac function was observed in the zebularine treated MSC-seeded scaffold group as compared to the MI control.Histological analysis also showed reduction in fibrotic scar,improvement in left ventricular wall thickness and preservation of ventricular remodeling in the zebularine treated MSC-seeded scaffold group.Immunohistochemical analysis revealed significant expression of cardiac proteins in DiI labeled transplanted cells and a significant increase in the number of blood vessels in the zebularine treated MSC-seeded collagen scaffold transplanted group.CONCLUSION Combination of 3D collagen scaffold and zebularine treatment enhances cardiac differentiation potential of MSCs,improves cell engraftment at the infarcted region,reduces infarct size and improves cardiac function.

Maternal Risk Factors and Short Term Outcome of Prematurity: A Descriptive Study at a Secondary Care Hospital

Background: Approximately 15 million babies are born premature (before 37 weeks of gestation) and 1 million babies die due to prematurity complications every year. Less is known about risk factors of prematurity in middle and low-income countries. The prevalence of prematurity ranges from 5% - 18%. Objective: To determine the prevalence of premature births and to assess the rate of survival, along with the morbidity, among preterm newborns. Furthermore, to document our experience with different gestational age groups of preterm births;and to analyze the association among these strata and their clinical outcomes. Study Design: A descriptive study. Place and Duration of Study: The Aga Khan Maternal and Childcare Centre Hyderabad, Pakistan, from 1st January 2017 to 31st December 2018. Methodology: All pregnant women registered at the obstetric clinic before 24 weeks of gestation having at least three subsequent visits at the same clinic were included in the study. The women who were lost to follow up before completing three visits were excluded from the study. All un-booked women were also excluded from the study. Demographic profile was recorded including maternal age, parity, no of visits at the clinic, gestational age, mode of delivery, birth weight and pregnancy outcome. Newborns were subsequently followed at nursery or well-baby till discharge. Further subgroups were made for gestational age to assess the frequency of various morbidities in each group. Results: One thousand and ninety-one (1091) women were included in the study period that fulfilled the inclusion criteria. Two pregnancies were terminated before 24 weeks due to major congenital malformations. The prevalence of prematurity was recorded as 13.4% (146/1089). Perinatal mortality rate (no of stillbirths plus the number of early neonatal death/1000 live birth) was 17 (15.6/1000 live births) out of them, 12 were still births and 5 were early neonatal death. Out of the total preterm babies born, 59.5% (87/146) were admitted to the nursery. In the study group (2%/3146) were extreme preterm, while 7.5% were severe preterm (11/146). Moderate preterm was 11.6% (17/146) and the majority were late preterm accounting for 78.7% (115/146). Though the incidence of birth asphyxia were noted more in late preterm babies i.e. 10 as the number of these babies are also high in our study but the overall percentage was low (8.7%) as compared with the babies of extreme prematurity (100%) and moderate late prematurity (23.5%) respectively. In pregnancy outcome, 12 were still births in which six (50%) were in the late preterm group. Total of 17 newborns suffered from birth asphyxia in which ten newborns (58.8%) were in late preterm group. Overall, it was noted that the decreasing gestational age was directly correlated to morbidity and mortality. Conclusion: Among the different strata, the late preterm group has been observed to be associated with greater morbidity and mortality. Prior awareness of the morbidities associated with late preterm babies is helpful for the health care providers to anticipate and manage potential complications in preterm infants.

A novel HPTLC method for quantitative estimation of biomarkers in polyherbal formulation

Objective: To explore the quantitative estimation of biomarkers gallic acid and berberine in polyherbal formulation Entoban syrup.Methods: High performance thin layer chromatography was performed to evaluate the presence of gallic acid and berberine employing toluene: ethyl acetate: formic acid:methanol 12:9:4:0.5(v/v/v/v) and ethanol: water: formic acid 90:9:1(v/v/v), as a mobile phase respectively.Results: The R f values(0.58) for gallic acid and(0.76) for berberine in both sample and reference standard were found comparable under UV light at 273 nm and 366 nm respectively. The high performance thin layer chromatography method developed for quantization was simple, accurate and specific.Conclusions: The present standardization provides specific and accurate tool to develop qualifications for identity, transparency and reproducibility of biomarkers in Entoban syrup.

Emerging role of biosimilars in the clinical care of inflammatory bowel disease patients

The increasing incidence of inflammatory bowel disease(IBD)globally has redirected the healthcare system's focus towards safe and affordable pharmacological interventions.The inception of anti-tumor necrosis factor-α(TNF-α)had resulted in a trend shift from surgical interventions.However,as the patents of approved anti-TNF-αdrugs expire,biological copies of the many approved products are in the pipeline.The most commonly used biosimilar for IBD has been infliximab,followed by Adalimumab biosimilars which have been approved in major countries across the world.Although biosimilars are approved on the basis of similarity of their reference product,the lack of real-world evidence of its safety in ulcerative colitis and Crohn’s disease patients has contributed to physicians’hesitancy.However,biosimilars are expected to reduce treatment costs and provide economic benefits.