From Molecular Pathology of COVID 19 to Nigella Sativum as a Treatment Option: Scientific Based Evidence of Its Myth or Reality / 中国结合医学杂志

COVID-19 virus is a causative agent of viral pandemic in human beings which specifically targets respiratory system of humans and causes viral pneumonia. This unusual viral pneumonia is rapidly spreading to all parts of the world, currently affecting about 105 million people with 2.3 million deaths. Current review described history, genomic characteristics, replication, and pathogenesis of COVID-19 with special emphasis on Nigella sativum (N. sativum) as a treatment option. N. sativum seeds are historically and religiously used over the centuries, both for prevention and treatment of different diseases. This review summarizes the potential role of N. sativum seeds against COVID-19 infection at levels of in silico, cell lines and animal models.

Lack of uniformity in screening, diagnosis and management of gestational diabetes mellitus among health practitioners across major cities of Pakistan

Objective: To determine knowledge, attitude and practice [KAP] regarding management of Gestational Diabetes Mellitus [GDM] among Health Care Providers in major cities of Pakistan

Methods: A knowledge, attitude and practice [KAP] questionnaire based study was conducted in major cities in Pakistan from health care providers in public and private hospitals and clinics. Questionnaires were provided to the health care providers regarding screening, diagnosis and management of patients with GDM. Data analysis was done using IBM SPSS 20

Results: A total of 210 doctors took part in the study. 55[26%] reported using fasting blood glucose as screening test for GDM whereas 129[61.4%] respondents used Oral Glucose Tolerance based WHO criteria for diagnosing GDM. Thirty six [17%] and 98[46.7%] doctors referred their patients to Gynecologists. For treating GDM, 64[30.5%] doctors prescribed insulin [NPH/Regular, 70/30 Mix]. 112[53.5] doctors used combination of capillary glucose by glucometer and plasma blood glucose tests for monitoring of glycemic control of patients with GDM

Conclusion: There is lack of agreed screening tests and criteria for diagnosis and management of GDM patients. Doctors need to be educated to follow evidence based diagnostic and management guidelines so that GDM patients can be effectively managed. Recently released South Asian Federation Societies and Pakistan Endocrine Society guidelines could be much needed consensus guidelines for doctors to apply in their daily practice to improve GDM diagnosis and treatment

simple integrated primary health care based model for detection of diabetic retinopathy in resource-limited settings in Pakistani population

Objective: To find out prevalence of Diabetic Retinopathy in general population of three districts in Pakistan

Methods:A community based cross-sectional survey was conducted in three large districts of Pakistan namely Rawalpindi in Punjab, Peshawar in Khyber Pakhtoonkhwa and Hyderabad in Sindh between January 2013 and August 2015. Lady Health Workers identified individuals at high risk for diabetes based on predefined criteria. High risk population was tested for dysglycemia. Fundoscopic evaluation for evidence of DR was performed in all individuals with a random blood glucose >190mg/dl. Individuals with the evidence of DR were referred to affiliated tertiary care ophthalmology departments

Results:A total of 42,629 individuals reported at the project sites and 63% [n=26,859] were female. Fifty one percent [n=21,989] individuals met high risk criteria. Out of these 21,989 individuals, dysglycemia was found in 3,869 [17.6%]. Fundoscopy showed evidence of DR in 1,042 [27%] individuals. Amongst high risk population, dysglycemia was significantly more common in females as compared to males. The frequency of DR in dysglycemic patients was comparable across both gender groups

Conclusion:The prevalence of DR in Pakistani population is alarmingly high. This preventable cause of blindness is largely undiagnosed in our population and a simple integrated model based on primary health care facilities can help identify and treat a large population of DR patients

Causes of short stature in Pakistani children found at an Endocrine Center

Background and Objective: Short stature is defined as height below 3[rd] centile. Causes of short stature can range from familial, endocrine disorders, chronic diseases to chromosomal disorders. Most common cause in literature being idiopathic short stature. Early detection and management of remedial disorders like malnutrition and vitamin D deficiency, Endocrine disorders like growth hormone deficiency and hypothyroidism can lead to attainment of expected height. Pakistani data shows idiopathic short stature as the most common cause of short stature. Our study aimed at detecting causes of short stature in children/adolescents at an Endocrine referral center

Methods: A retrospective study was conducted at WILCARE Center for Diabetes, Endocrinology and Metabolism, Lahore on 70 well-nourished children/adolescents. The patients had been evaluated clinically, biochemically and radiologically as needed. Biochemical testing included hormonal testing as well to detect endocrine causes. Data was entered and analyzed in SPSS 20.0

Results: Leading cause of short stature in our population was Growth Hormone [GH] deficiency seen in 48 out of 70 [69%] patients. Second most common endocrine abnormality seen in these patients was Vitamin D deficiency [44 out of 70 patients [63%]]. Primary hypothyroidism; pan-hypopituitarism and adrenal insufficiency were other endocrine causes. The weight for age was below 3rd percentile in 57 [81%] patients, with no association with other major causes

Conclusion: Growth hormone and Vitamin D deficiency constitute one of the major causes of short stature among well-nourished children with short stature in Pakistan

Effect of long standing time on bone mineral density in middle aged males

Background: Bone mineral density [BMD] is an important tool for assessing the risk of an individual for acquiring fractures. The determinants of bone mineral density are not well defined in men. The study aims at assessing the bone mass in middle aged men having occupations which required prolonged standing

Methods: Across sectional study was carried out comparing the T-score values of BMD of 100 men having a daily standing time of more than 8 hours to 100 men having a daily standing time of less than 3 hours

Results: The results showed increased bone mass in men with jobs requiring prolonged standing as compared to men, which had a sedentary life style

Conclusion: Middle aged men leading an active life style, having no other established risk factor for osteoporosis, have a less chance of developing decreased bone mass in future compared to men having jobs which require a lot of sitting, so that the lack of baseline physical activity predisposes them for an osteoporotic fracture in later life

Alternative tool to bone densitometry in ruling out osteoporosis in postmenopausal women between the age of 50 and 65 years

To devise an alternate tool to bone densitometry in ruling out osteoporosis in postmenopausal women between the age of 50 and 65. A descriptive cross-sectional study was conducted on a sample of 200 females aged between 50 and 65, from 1st November 2002 to 15th January 2003. North Medical Ward, Unit-4 and Out Patient Clinics, Mayo Hospital, and Akram Medical Complex, Lahore. Main outcome measures: Application of a tool based on the risk factor assessment in postmenopausal women as an alternative to bone densitometry in ruling out osteoporosis. The study results showed that in postmenopausal women between the ages of 50 and 65 years without any major risk factors as assessed by using the questionnaire, the occurrence of osteoporosis was not evident although bone weakness of varying degrees was observed in 30.5% of the study sample. This tool thus provides us with an inexpensive and efficient way of ruling out osteoporosis in postmenopausal women between the ages of 50 and 65 years without assessing their BMD values

COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data

COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.

Aprepitant as a combinant with Dexamethasone reduces the inflammation via Neurokinin 1 Receptor Antagonism in severe to critical Covid-19 patients and potentiates respiratory recovery: A novel therapeutic approach

BackgroundCorona virus infection is a respiratory infection, compromising the normal breathing in critical patients by damaging the lungs. Researches are ongoing to find an efficient treatment strategy for this disease by either inactivating the virus or boosting the immune system of patient or by managing the cytokine storm. AimTo evaluate the clinical outcomes of Substance P receptor Neurokinin 1 antagonist in Covid-19 patients against the usual treatments as controls. Patients and MethodsIt is a randomized clinical trial, open label, having two arms, one receiving normal management and care while other receiving Neurokinin-1 Receptor antagonist, Aprepitant, in addition. Dexamethasone, a corticosteroid is also administered orally to both the groups. PCR positive, hospitalized patients with more than 18 years of age, both genders, moderate to critical phase were included. 18 patients were randomly allocated in both arms, having 10 in group A and 8 in group B. Lab investigations were performed in both the groups before and after the intervention. We report preliminary results for the comparison of Aprepitant 80 mg given once daily for 3-5 days vs routine management. The primary outcome was total in hospital days and duration of disease. ResultsMean age of patients in group A was 47.63 {+/-}12.07years while 60.90{+/-} 9.75 years in group B. There were 3/8 males in group A and 8/10 in group B. There were 2 critical patients in group A and 5 in group B. Biochemical and hematological parameters in both groups didnt show much difference except the C-reactive protein reduction in the intervention group, indicative of a reduced inflammation. Oxygen saturation also improved but more patients should be enrolled to get a statistically significant data. One patient was discharged from each group within 5 days and one patient expired in each. ConclusionsIt is a pilot study but the findings give a strong clue for the therapeutic potential of Aprepitant. Patients who received a combination therapy of Aprepitant and Dexamethasone were recovered earlier and showed improved clinical outcomes, laboratory findings and reduced C-reactive protein which is an inflammatory marker. We suggest here a study on larger sample size to get a deeper insight of its potential and efficacy. It may be more effective in severe to critical patients having respiratory difficulties.

Epidemiology, Clinico-Pathological Characteristics, and Comorbidities of SARS-CoV-2 infected Pakistani Patients

SARS-CoV-2 is a causative agent for COVI-19 disease, initially reported from Wuhan, China. Infected Patients experienced mild to severe symptoms, resulting in several fatalities due to a weak understanding of its pathogenesis, which is the same even to date. This cross-sectional study has been designed on four hundred and fifty-two symptomatic, mild-to-moderate, and severe/critical patients to understand the epidemiology and clinical characteristics of COVID-19 patients with their comorbidities and response to treatment. The mean age of studied patients was (58{+/-}14.42) years, and the overall male to female ratio was 61.7 to 38.2%, respectively. 27.3% of the patients had a history of exposure, 11.9% travel history, while for 60% of patients, the source of infection was unknown. The most prevalent signs and symptoms in ICU patients were dry coughs, myalgias, shortness of breath, gastrointestinal discomfort, and abnormal Chest X-ray (p<0.001), along with the high percentage of hypertension (p=0.007) and COPD (p=0.029) as leading comorbidities. Complete Blood Counts indicators were significantly increased in severe patients, while the Coagulation Profile and D-dimer values were significantly higher in mild-to-moderate (non-ICU) patients (p < 0.001). Serum Creatinine (1.22 umole L-1; p = 0.016) and LDH (619 umol L-1; p < 0.001) indicators were significantly high in non-ICU patients while, raised values of Total Bilirubin (0.91 umol L-1; p = 0.054), CRP (84.68 mg L-1; p = 0.001) and Ferritin (996.81 mg L-1; p < 0.001) were found in ICU patients. Drug Dexamethasone was the leading prescribed and administrated medicine to the COVID-19 patients, followed by Remdesivir, Meropenem, Heparin, and Tocilizumab, respectively. A characteristic pattern of Ground glass opacities (GGO), consolidation, and interlobular septal thickening were prominent in severely infected patients. These findings could be used for future research, control, and prevention of SARS-CoV-2 infected patients.

SARS-CoV-2 variants of concern dominate in Lahore, Pakistan in April 2021

BackgroundThe SARS-CoV-2 pandemic continues to expand globally, with case numbers rising in many areas of the world, including the Indian sub-continent. Pakistan has one of the world s largest population, of over 200 million people and is experiencing a severe third wave of infections caused by SARS-CoV-2 that begun in March 2021.In Pakistan, during third wave until now only 12 SARS-CoV-2 genomes have been collected and among these 9 are from Islamabad. This highlights the need for more genome sequencing to allow surveillance of variants in circulation. In fact more genomes are available among travellers with a travel history from Pakistan, than from within the country itself. MethodsFor a better understanding of the circulating variants in Lahore and surrounding areas with a combined population of 11.1 million, within a week of April 2021, 102 samples were sequenced. The samples were randomly collected from 2 hospitals with a diagnostic polymerase chain reaction (PCR) cutoff value of less than 25 cycles. ResultsAnalysis of the lineages shows that B.1.1.7 (first identified in the UK, Alpha variant) dominates, accounting for 97.9% (97/99) of cases, with B.1.351 (first identified in South Africa, Beta variant) accounting for 2.0% (2/99) of cases. No other lineages were observed. DiscussionIn depth analysis of the B.1.1.7 lineages indicates multiple separate introductions and subsequent establishment within the region. Eight samples were identical to genomes observed in Europe (7 UK, 1 Switzerland), indicating recent transmission. Genomes of other samples show evidence that these have evolved, indicating sustained transmission over a period of time either within Pakistan or other countries with low density genome sequencing. Vaccines remain effective against B.1.1.7, however the low level of B.1.351 against which some vaccines are less effective demonstrates the requirement for continued prospective genomic surveillance.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We conducted a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine was 1.11 (95% CI: 1.02, 1.20; I2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine was associated with increased mortality in COVID-19 patients, and there was no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.