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Objective: We assessed the effectiveness of oral Hydroxychloroquine (HC), Azithromycin (AZ) and Oseltamivir (OS), alone or combined, among patients hospitalized with mildly symptomatic coronavirus infectious disease (COVID-19). Methods: Following the approval of the National Bioethics Committee and prospective registration (clinicaltrials.gov NCT04338698), a multicenter randomized clinical trial of adaptive design was conducted at 10 multispecialty hospitals in Pakistan. Patients were randomized into seven treatment groups. Starting April 15, 2020, consenting, eligible, otherwise healthy adult patients or those with co-morbidities under control, were recruited if they presented with mildly symptomatic COVID-19 (scored 3 on a 7-point ordinal scale anchored between 1 = not hospitalized, able to undertake normal activities, to 7 = death) confirmed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Two primary outcomes were assessed by day seven: Turning qRT-PCR negative; and clinical improvement of two points from the baseline. Outcome rates were compared using a chi-square test. Multiple imputations were applied to handle missing data. An interim data analysis was carried out on July 19, 2020, following which the study continued without treatment group changes. Data Safety and Monitoring Board advised to stop recruitment due to its futility on January 18, 2021. Results: Of 471 patients randomized, a total of 426 (90.4%) completed the follow-up for primary outcomes. Based on imputed data analyses at day seven: Total qRT-PCR negative cases were 137/471 (29%, 95% CI 25.0 - 33.4). By day seven, a total of 111/471 (23.5%, 95% CI 19.8 - 27.6) showed clinical improvement. No serious or non-serious adverse event was reported. Conclusions: Among patients with mild COVID-19, there was no statistically significant difference in the effectiveness of oral antimalarial, antiviral, or antibiotic treatments. [ABSTRACT FROM AUTHOR]

Objective: To compare the neuro-radiologic findings in Systemic lupus erythematosus (SLE) patients with and without antiphospholipid antibodies (aPL) in different neuro-psychiatric manifestations. Methods: This cross-sectional comparative study was carried out at King Khalid University Hospital, a tertiary care teaching hospital, Riyadh, Saudi Arabia from June 2012 to January 2015. Ninety seven SLE patients with neuro-psychiatric manifestations were included in the study and divided into two groups. Group I (50 patients) SLE with aPL and group II (47 patients) SLE without aPL. We compared Demographic features, clinical manifestations and magnetic resonance imaging (MRI) brain findings. Results: Demographic and clinical characteristics of two groups were similar. In Group-I, anticardiolipin antibodies (aCL) were most common (86%). In patients with headache, most of the patients in Group-I had white matter hyperintensities (WMHIs) (50% vs 27%) while most of the patients in Group-II had normal MRI brain (38% vs 73%). Similarly WMHIs were found more in Group-I patients with seizures (60% vs 21%), while ischemia/infarction, atrophy and normal MRI were found in Group-II. MRI brain in patients with neurological deficit and psychiatric disorder were not much different in both the groups. Conclusion: We found no statistically significant differences in frequencies of MRI brain abnormalities in SLE patients with and without aPL antibodies. Each of the three aPL may have a variable effect on the brain. [ABSTRACT FROM AUTHOR]

Some cases of psoriatic arthritis (PsA) cannot be explicitly diagnosed, especially when the skin and nail lesions present years after the joint disease or are absent. Autoimmunity may also play a role in the development of Dupuytren's disease. However, the simultaneous presence of PsA and Dupuytren's disease is very rare. We present a patient displaying arthritis in multiple small joints, with bone erosions and bony fusions in all four extremities, combined with Dupuytren's disease. Because of the atypical clinical manifestation, the diagnosis perplexed doctors for decades. Without formal treatment, the disease followed a natural course over time. Reviewing the patient's data, a potential diagnosis of PsA, combined with Dupuytren's disease, was eventually made. After surgery, contractures of palmar and plantar fascia as well the thumb web were released, and the hallux valgus was corrected. [ABSTRACT FROM AUTHOR]

Objective: To screen Haemophilia-A patients for five known recurrent F8 gene variants and to analyze CA repeats in intron 13 of F8 gene in the mother and the affected child pairs., Methods: In this descriptive cross sectional study, 80 unrelated pairs of "mother and son" affected by Haemophilia-A were recruited as subjects. After collection of samples DNA was extracted using the Chelex (Bio-Rad, USA) method. Five known F8 gene variants were screened in the mothers and the affected sons by the allele specific PCR. The amplified products were separated on 2% agarose gels.CA repeats in intron 13 of the F8 gene in the mother and the affected child pairs were analyzed by Sanger sequencing method. The CA repeat alleles were used to look for the feasibility of linkage based diagnosis of Haemophilia-A in the affected families. The data were analyzed using Statistical Package for Social Sciences (SPSS) version 22.0., Results: In the 80 subject "mother and son" pairs a recurrent F8 gene variant was found in 32 pairs (40%). The most recurrent variant c.6869G>A was seen in 12 (15%). Linkage based analysis of the CA repeats in intron 13 was found to be informative in 29 (36.2%) mother-son pairs., Conclusion: The five known Haemophilia-A disease causing variants were found in 40% of the Pakistani Haemophilia-A patients. The five recurrent F8 gene variants and the CA repeats in intron 13 of F8 gene can provide a comprehensive basis for carrying out prenatal diagnosis and carrier screening in majority of the Pakistani Haemophilia-A families., Competing Interests: Conflict of interest: This study has no conflict of interest to declare by any author., (Copyright: © Pakistan Journal of Medical Sciences.)

Objectives: To determine differential expression of microRNAs (miRNAs) in plasma of 2, 4, 6-Trinitrotoluene (TNT) exposed ordnance factory workers., Methods: A case control study was conducted at the Department of Toxicology, Armed Forces Institute of Pathology, Rawalpindi from July to December 2020. A total 30 subjects were recruited from an ordnance factory that were directly exposed to TNT and 120 non-exposed individuals from non-factory healthy population. Plasma levels of five miRNAs including miRNA-let-7a-2, miRNA-34a-1, miRNA-21-2, miRNA-106b-1, miRNA-122a-1 were measured by quantitative real-time polymerase chain reaction (RT-PCR)., Results: Micro RNAs showed a wide range of Ct (cycle threshold) values ranging from 23.48 to 41.94. Among the five miRNAs let-7a-2 and miRNA-122a-1 displayed relatively high expression with Ct values ranging from 26.58 ± 2.25 to 27.18 ± 0.80 respectively. Relative fold change expression for all five miRNAs of exposed individuals were found high ( p <0.0001) vs non-exposed. Dividing fold change expression of exposed individuals into two groups as ≤ 10 and > 10, the individuals having ≤ 10-fold change expression were19 (63.3%) in miRNA-let-7a-2, 30 (100%) in miRNA-34a-1 and 23 (76.7%) in miRNA-122a-1 while in miRNA-21-2 and miR-106b-1, 23 (76.7%) and 18(60%) individuals had > 10-fold change expression respectively. Among the five miRNAs in exposed individuals, miRNA-let-7a-2, miR-21-2, miR-106b-1 and miR-122a-1 were found highly expressed with fold change expression > 10 ( p <0.0001). No significant association was found between miRNAs expression levels with age and working duration., Conclusion: The study shows upregulation of all five miRNAs in TNT exposed subjects with no significant association of expression levels with age and working duration ., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Objectives: to determine the relationship of 374T/A (rs1800624) polymorphism in the gene encoding RAGE with Type-2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and serum soluble RAGE (sRAGE) level in Pakistani patients., Methods: A case-control study, conducted from January 2017 to December 2018, involving 150 healthy controls (HC), 150 T2DM patients with no retinopathy (DNR) and 150 DR patients diagnosed by coloured fundus photography. Tetra-primer amplification refractory mutation system - polymerase chain reaction (T-ARMS-PCR) was used for genotyping. Serum sRAGE levels were measured by enzyme-linked immunosorbent assays (ELIZA)., Results: The frequency of TT, TA and AA genotypes of rs1800624 polymorphism were: 92.7%, 6%, 1.3% in HC, 80%, 17.3%, 2.7% in DNR and 76.7%, 19.3%, 4.3% in DR groups. Heterozygous TA genotype and mutant A allele showed significant association with diabetes and DR vs HC. In dominant model, mutant allele showed significant association with DNR and DR vs HC. No significant association of rs1800624 was detected with DR and its sub-groups, non-proliferative DR (NPDR) and proliferative DR (PDR) vs DNR. Dividing NPDR into mild, moderate and severe, heterozygous TA genotype showed significant association with moderate and severe NPDR vs DNR. In DNR and DR groups, TA genotype was significantly associated with raised sRAGE., Conclusion: rs1800624 RAGE gene polymorphism might be a risk factor for T2DM and NPDR in Pakistani patients. Raised sRAGE levels have a positive correlation with PDR and are associated with heterozygosity of rs1800624 polymorphism in DNR and DR groups., (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: To evaluate the association of miR-196a rs11614913 C/T genetic variation and its target gene annexin A 1 mRNA expression with breast cancer risk in Pakistani female ethnicities., Methods: This case control study, conducted from March 2017 to November 2018 included 295 breast cancer patients, 295 controls of three Pakistani ethnicities and archived 100 samples of cohort group for genotyping and expression profiling. Genotyping of miR-196a (rs11614913 C/T) was done by ARMS PCR technique. Annexin-A1 ( ANXA1) mRNA expression was measured with qRT-PCR and detection of protein expression of ANXA1 was done by immunohistochemistry., Results: CC homozygous genotype of miR-196a rs11614913 was present in 81.4% of cases and 73.9% controls. C/T polymorphism was found to be significantly associated with decrease risk of breast cancer (OR=0.25 (0.11- 0.58, p <0.05). Similar trend was seen with the minor T allele (OR=0.55 (0.39-0.77, p <0.05, and both dominant and recessive models (OR=0.64; p =0.02 and OR=0.26, p =0.00). In the KPK ethnic group significant decrease association with breast cancer risk was observed (OR= 0.22 (0.09-0.53, p < 0.05). Immunohistochemical staining showed loss of ANXA1 protein expression in 72 samples, and significant association was observed with pathological type p =0. 00 and triple negative receptor status p =0.03 and with genotypes of miR-196a p =0.00. Increase relative expression of 2.81± .88 by qPCR analysis of ANXA1 mRNA was noted with TT genotype., Conclusions: Our results demonstrate that miR-196a rs11614913 C/T polymorphism is associated with a decreased risk and loss of protein expression in breast cancer in the Pakistani population., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background and Objective: The use of over the counter medications (OTCMs) is a common practice globally. OTCMs are of special concern among pregnant women as they pose risk to the mother and fetus. The objective was to assess the use of OTCMs by pregnant woman, and factors associated with it., Methods: A cross-sectional study, using a structured self-administrated questionnaire was conducted at the obstetric and antenatal clinics at King Khalid University hospital, Riyadh. 354 pregnant women were surveyed., Result: About 32% of the study participants used OTCMs without prescription at least once during their last pregnancy. The most commonly used OTCM was Paracetamol (22%). Pharmacists were the main source of knowledge (53%) for the participants. Correct knowledge regarding the drugs was associated with the usage of OTCM drug., Conclusion: Use of OTCMs and antibiotics during pregnancy is a common practice among Saudi pregnant women. General awareness regarding OTCMs use during pregnancy without prescription needs to be raised in the community. Pharmacists and media can help in providing accurate knowledge., Competing Interests: Declaration of interest: The authors have no conflict of interest.

Objective: To uncover the pulmonary manifestations of Systemic Lupus Erythematosus (SLE) patients alone and to compare findings with antiphospholipid syndrome (APS) associated with SLE., Methods: This cross sectional comparative study was carried out at King Khalid University Hospital (KKUH)/King Saud University (KSU), a tertiary care hospital, Riyadh, Kingdom of Saudi Arabia. From June 2012 to March 2014, 96 diagnosed SLE patients with respiratory symptoms were included in the study and divided into two groups. Group one included SLE without antiphospholipid syndrome (APS) and group two SLE with APS. We compared Demographic features, clinical manifestations and findings of chest X-Ray, Arterial Blood Gases, Pulmonary function tests, six minute walk test, ventilation perfusion scan, echocardiography and chest high resolution computed tomography., Results: Demographic and clinical characteristics of two groups were similar. Previous history of deep venous thrombosis (3% vs 27.6%, p=0.001), pulmonary embolism (3% vs34.5%, p<0.0001) and abortions (7.5% vs 27.6%, p=0.019) were significantly more in group two. Levels of Anticardiolipin antibody (0% vs 100%, p<0.0001) and lupus anticoagulant (1.5% vs 79.3%, p<0.0001) were also significantly higher in group two. Hypoxemia measured by pulse oximetry (43.3% vs 65.5% p=0.045, pulmonary Arterial Hypertension (15.5% vs 39.3% p=0.014)), and pulmonary embolism (3.4% vs 21.4% p=0.013) and ventilation perfusion mismatch on V/Q scan (1.5% vs 24.1% p=0.001) were more frequent in group two., Conclusion: Hypoxemia, pulmonary embolism and pulmonary arterial hypertension were significantly high in SLE patients with APS, requiring long term anticoagulation and treatment and close follow-up.