Short-term adverse effects of COVID-19 vaccines after the first, second, and booster doses: a cross-sectional survey from Punjab, Pakistan, and the implications

ABSTRACT Background: Safety and efficacy concerns regarding coronavirus disease 2019 (COVID-19) vaccines are common among the public and have a negative impact on their uptake. We aimed to report the adverse effects currently associated with the vaccine in Pakistan to build confidence among the population for its adoption. Methods: A cross-sectional study was conducted in five districts of the Punjab province of Pakistan between January and March 2022. The participants were recruited using convenience sampling. All data were analyzed using SPSS 22. Results: We recruited 1622 people with the majority aged between 25-45 years. Of these, 51% were female, including 27 pregnant women and 42 lactating mothers. Most participants had received the Sinopharm (62.6%) or Sinovac (17.8%) vaccines. The incidences of at least one side effect after the first (N = 1622), second (N = 1484), and booster doses (N = 219) of the COVID-19 vaccine were 16.5%, 20.1%, and 32%, respectively. Inflammation/erythema at the injection site, pain at the injection site, fever, and bone/muscle pain were common side effects of vaccination. No significant differences were observed in the adverse effect scores between all demographic variables except for pregnancy (P = 0.012) after the initial dose. No significant association was observed between any variable and the side effect scores of the second and booster doses of the vaccine. Conclusions: Our study showed a 16-32% prevalence of self-reported side effects after the first, second, and booster COVID-19 vaccinations. Most adverse effects were mild and transient, indicating the safety of different COVID-19 vaccines.

Therapeutic potential and bioactive phenolics of locally grown Pakistani and Chinese varieties of ginger in relation to extraction solvents

Abstract Current study compares the Therapeutic/nutra-pharmaceuticals potential and phenolics profile of Pakistani grown Pakistani and Chinese varieties of ginger. Crude yield of bioactive components from the varieties tested, using different extraction solvents including chloroform, ethyl acetate, ether, methanol, ethanol and distilled water. The crude bioactives varied from 14.1-82.5%. The highest extraction yield was noted for Pakistani species. The HPLC analysis revalued significant amounts of phenolics including vanillin, protocatechuic, vanillic, ferulic, sinapinic and cinnamic acids. The highest anti-inflammatory activity was shown by ethanolic extract of Pakistani variety (IC50: 26.5±1.8) whereas Chinese variety exhibited potent anticancer potential against MCF-7 cell line (Inhibition: 91.38 %). The Chinese variety in general showed higher phenolics and anticancer, while the Pakistani exhibited higher anti-inflammatory activity. Pakistani grown ginger and ethanolic extract of Chinese ginger showed highest antimicrobial activity against Pseudomonas aeruginosa 18.0±0.02 & 15.00±0.02 mm respectively. Minimum results obtained with water for both varieties of ginger with range of 7.2±0.22 and 6±0.07 respectively. Moreover, the phenolics composition, anti-inflammatory, antibacterial and anticancer activities of both tested varieties of ginger were notably affected as a function of extraction solvents. Our findings advocate selection of appropriate solvent for recovery of effective phenolic bioactive compounds from ginger verities to support the Nutra-pharmaceutical formulation.

A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

Chemical characterization, docking studies, anti-arthritic activity and acute oral toxicity of Convolvulus arvensis L. leaves

Objective: To evaluate acute oral toxicity and anti-arthritic activity of the methanolic extract of Convolvulus arvensis L. leaves. Methods: Safety was assessed by acute oral toxicity (OECD 425) study. Anti-arthritic activity was explored by in vitro (inhibition of protein denaturation) and in vivo (Complete Freund's adjuvant-induced arthritis and carrageenan-induced inflammation) methods. Antioxidant potential was determined by assessing ferric reducing power, DPPH inhibition, and H

Chemical characterization, docking studies, anti-arthritic activity and acute oral toxicity of Convolvulus arvensis L. leaves

Objective: To evaluate acute oral toxicity and anti-arthritic activity of the methanolic extract of Convolvulus arvensis L. leaves. Methods: Safety was assessed by acute oral toxicity (OECD 425) study. Anti-arthritic activity was explored by in vitro (inhibition of protein denaturation) and in vivo (Complete Freund's adjuvant-induced arthritis and carrageenan-induced inflammation) methods. Antioxidant potential was determined by assessing ferric reducing power, DPPH inhibition, and H2O2 scavenging assays. Furthermore, molecular docking was done to check interactions between the plant constituents and cyclooxygenases (COX-1 and COX-2). Quercetin, gallic acid, caffeic acid, syringic acid, sinapic acid, and vanillic acid were quantified by HPLC and eight compounds were identified by GC-MS analysis. Results: No mortality and abnormality in biochemical parameters were observed in the toxicity study. Histological analysis of vital organs also supported these biochemical results. The in vitro and in vivo studies showed that the methanolic extract of leaves of Convolvulus arvensis exhibited dose-dependent anti-arthritic and anti-oxidant potential. Molecular docking showed better interactions of plant compounds with cyclooxygenases as compared to standard ibuprofen. Conclusions: Convolvulus arvensis exhibits strong anti-arthritic activity, justifying the traditional use of the herbal drug.

Influence of Ozagrel Sodium along Atypical Anti-psychotic Drug on Red Blood Cell Distribution Width in Rats with Minimum and Maximum Dose Comparison

Objective: To study the activity of ozagrel sodium alone and in combination with the atypical antipsychotic drug on Red blood cell distribution width (RDW-CV) along with different doses and their comparison in rats. Method: This experimental study consisted of 120 albino rats of both gender, they were of 310-350 g, there were 10 groups which consists of each of 12 rats (n=12). Rats were treated with an accurate dose of ozagrel and atypical antipsychotic (Zuclopenthixol cis isomer of clopenthixol) alone and in combination for 3-weeks (21 days). We obtained blood sample at 0, 7th, 14th and last day of the study. Red blood distribution widths were measured from blood tests by utilizing standard medical laboratory technique. Red blood cell distribution width (RDW-CV) was measured by using the coefficient of variation indicator. Results were gathered and summarized by applying statistics. The comparison was formed between all days value to zero-day. Results: Minimum dose treated groups by both medications showed an increase and RDW-CV, but maximum dose showed p<0.001 decreases in RDW-CV in individual groups of drugs treatment and in case of RDW-CV maximum dose showed an increasing trend with p<0.001 in the combination groups. Conclusion: Maximum dose of ozagrel may cause a decrease in RDW-CV alone and it may cause an increase in (RDW-CV) with a combination of atypical antipsychotic drug.

Role of 5% Imiquimod Cream in the Prevention of Recurrence of Keloids Post Shave Excision

Introduction: Keloids represent an excessive connective tissueresponse to injury, which may be trivial. Despite numeroussmall case series advocating a wide range of therapies, there isno level one evidence for any single treatment. This study wasdone to know the role of 5% imiquimod cream in preventingrecurrence of excised keloids.Material and methods: Study was done on 30 Cases ofkeloids attending the Department of DVL, Osmania generalhospital for a duration of 6 months from December 2017 toMay 2018.Results: It was observed that after 6 months, 7 of 8 keloidson the trunk and 4 of the 6 keloids on the extremities hadevidence of recurrence while of 14 auricular keloids, only2 had evidence of recurrence and none of the keloids in thesuprapubic region had evidence of recurrence.Conclusion: According to the present study the use ofpostoperative, topically applied imiquimod following shaveexcision is a more effective intervention compared to thestandard, complete excision of keloids.

Pathologic complete response in HER2-positive breast cancer patients receiving trastuzumab in neoadjuvant setting

Objective: To compare the pathological complete response in human epidermal growth factor receptor type 2 [HER-2] positive breast cancer patients getting neoadjuvant chemotherapy with or without trastuzumab

Study Design: Retrospective randomised double-arm observational study

Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2008 to 2016

Methodology: HER2-positive, lymph node positive, breast cancer patients receiving neoadjuvant chemotherapy [NACT] were retrospectively observed. Patients getting neoadjuvant trastuzumab, fulfilling the inclusion criteria were studied. The comparison group included randomly selected equal number of HER2-positive breast cancer patients having similar tumor characteristics, getting NACT only. Pathological complete response [pCR] was defined as no residual invasive or in situ residual tumor in breast tissue, or in the lymph nodes. One hundred and fifty-six patients were studied. Eighty-nine patients with HER2-positive disease received trastuzumab preoperatively. Sixty-four [n=64] patients received the complete standard dose of neoadjuvant trastuzumab along with chemotherapy. Almost equal number of patients [n=67] with HER2- positive disease were selected by random assortment for the reference group who did not receive trastuzumab before surgery

Results: The pathological complete response of study group was [n=32] 50%, which was 26.1% higher than the reference group [n=16] 23.9%; and this difference was statistically significant with a p-value of 0.002 [<0.05]. The overall pCR was 36.6% [n=48]

Conclusion: Addition of trastuzumab to neoadjuvant chemotherapy doubled the pCR in HER2-positive breast cancer. Targeted therapy should be offered to all eligible patients with HER2-overexpressing breast cancer

Plasmid-mediated mcr-1 gene in acinetobacter baumannii and pseudomonas aeruginosa: first report from pakistan

Abstract INTRODUCTION: The increased use of colistin against infections caused by Acinetobacter baumannii and Pseudomonas aeruginosa has resulted in colistin resistance. The purpose of this study was to detect plasmid-mediated mcr-1 gene in colistin-resistant A. baumannii and P. aeruginosa isolates. METHODS: A total of 146 clinical isolates of A. baumannii (n = 62) and P. aeruginosa (n = 84) were collected from the four largest tertiary care hospitals in Peshawar, Pakistan. All bacterial isolates were phenotypically screened for multidrug resistance using the Kirby-Baur disc diffusion method. The minimum inhibitory concentration (MIC) of colistin in all isolates was phenotypically performed using dilution methods. mcr-1 gene was detected through polymerase chain reaction and the nucleotide sequence of amplicon was determined using Sanger sequencing. RESULTS: Approximately 96.7% A. baumannii and 83.3% P. aeruginosa isolates were resistant to multiple antibiotics. Colistin resistance was found in 9.6% (6/62) of A. baumannii and 11.9% (10/84) of P. aeruginosa isolates. Among 16 colistin resistant isolates, the mcr-1 gene was detected in one A. baumannii (1.61% of total isolates; 16.6% of colistin resistant isolates) and one P. aeruginosa strain (1.19% of total isolates; 10% of colistin resistant isolates). Nucleotide BLAST showed 98-99% sequence similarity to sequences of the mcr-1 gene in GenBank. CONCLUSIONS: Our study reports, for the first time, the emergence of plasmid-mediated mcr-1-encoded colistin resistance in multidrug resistant strains of A. baumannii and P. aeruginosa. Further large scales studies are recommended to investigate the prevalence of this mode of resistance in these highly pathogenic bacteria.

Implications of early pregnancy obesity on maternal, fetal and neonatal health: retrospective cohort study from Oman

Objectives: This study aimed to determine the prevalence of early pregnancy obesity among Omani women and to review maternal antenatal complications, intrapartum and postpartum events and neonatal complications among such women in comparison to women of normal weight

Methods: This retrospective cohort study included 2,652 pregnant Omani women who delivered at the Royal Hospital, Muscat, Oman, between November 2011 and April 2012. The patients' electronic medical records were reviewed for antenatal, intrapartum and postpartum data. Body mass index was measured during the first trimester [

Results: In the study cohort, there were 901 [34%] obese women and 912 [34.4%] women of normal weight; of these, 440 [48.8%] and 672 [73.7%] had uncomplicated pregnancies, respectively. Obese women had a significantly increased incidence of gestational diabetes [relative risk [RR]: 2.23; 95% confidence interval [CI]: 1.70-2.92; P <0.01], gestational hypertension [RR: 3.04; 95% CI: 1.63-5.65; P <0.01], Caesarean delivery [RR: 1.48; 95% CI: 1.08-2.03; P <0.01], postpartum haemorrhage [RR: 2.10; 95% CI: 1.11-4.10; P = 0.01] and fetal macrosomia [RR: 2.71; 95% CI: 1.21-6.09; P <0.01]

Conclusion: Approximately one-third of the studied Omani women were obese. These women had a significantly increased risk of various maternal antenatal complications, intrapartum and postpartum events and neonatal complications

Borderline tumors of the ovary: a clinicopathological study

Objective: To report experience with borderline ovarian tumors [BOTs] in a developing country like Pakistan with limited resources and weak database of health system

Methods: Patients with BOTs managed at Shaukat Khanum Cancer hospital, Lahore, Pakistan from 2004 to 2014 were included and reviewed retrospectively. Data was recorded on histopathological types, age, CA-125, stage of disease, treatment modalities and outcomes

Results: Eighty-six patients with BOT were included with a median age of 35 years. Forty-two [49%] patients had serous BOTs and 43 [50%] had mucinous BOTs, while one [1%] had mixed type. Using FIGO staging, 80 patients had stage I; two patients had IIA, IIB and stage III each. Median follow-up time was 31.5 months. All patients had primary surgery. Seventy [81%] patients underwent complete surgical resection of tumor. Forty-three [50%] patients had fertility preserving surgery. Seventy-three [85%] patients remained in remission. Recurrent disease was observed in 13 [15%] patients. Median time to recurrence was 22 months. On further analysis, age above forty years, late stage at diagnosis and incomplete surgery were significantly associated with invasive recurrence

Conclusion: Despite a low malignant potential, relapses may occur in patients above forty years of age, incomplete surgery and staging information and advanced stage at presentation. Fertility sparing surgery should be considered in young patients. Complete excision of tumor and prolonged follow-up are advised because recurrence and transformation to invasive carcinoma may occur

Thinking out of the box: alternative career choices for young doctors in Pakistan

The number of young medical graduates in Pakistan is increasing every year. Most of whom wish to specialize in a particular clinical field. Considering the competition faced for specialty training selection and later on for job placement, it is suggested that these young graduates should explore some alternative careers as well. Opportunities can be availed and decision made based on graduates' personal interest, preference to work in Pakistan or abroad, and availability of suitable employment in local and international hospitals among other factors. Careers in the basic medical sciences, medical education, medical research, medical writing and bioethics can be considered, too. There are very few trained professionals in these fields in Pakistan and once trained, these young doctors will hopefully find rewarding employment

Surgical and visual outcomes of retinal detachment surgery in eyes with chorio-retinal coloboma

Objective: To evaluate the anatomical and visual outcome of surgical management of retinal detachment associated with chorio-retinal coloboma

Study Design: Prospective interventional case series

Place and Duration of Study: This study was conducted at Al-Shifa Trust Eye Hospital Rawalpindi from Jan 2012 to Dec 2013

Material and Methods: Twenty one eyes [21 patients] that underwent surgery for retinal detachment associated with chorio-retinal colobomas were selected. Evaluation was done on the basis of type of intervention, final visual acuity and anatomical outcome and complications. Out of 21, 19[90.47%] eyes underwent pars plana vitrectomy with silicone oil [SO] and 2[9.52%] underwent primary scleral buckling surgery. SO was removed in 9 [47.36%] eyes at final follow up. Encircling band was placed in 12 [63.15%] eyes based on peroperative judgment of surgeon. Intra-operative lensectomy was performed in 6 [28.57%] eyes. The main outcome measures were retinal re-attachment and visual recovery. Statistical analysis was performed using "IBM statistical package for social sciences [SPSS] Statistics" [version 17.0, Chicago, Illinois, USA]. Qualitative variables were described using percentage; quantitative data were defined using mean +/- standard deviation. The pre op and post op frequency of best corrected visual acuity [BCVA] was compared using Wilcoxan Signed Ranks Test. Confidence interval was 95% [level of significance p<0.05]

Results: The mean number of operations per eye were 1.57 +/- 0.74; mean follow-up was 13.1 months [range 12-18]. The retina remained attached in 18 eyes [85.71%] at final follow-up. The post op BCVA improved significantly as compared to pre op BCVA [p< 0.01]. Mean pre op BCVA was counting fingers [CF] and mean post op value of BCVA was 3/60

Conclusion: Pars plana vitrectomy along with silicon oil tamponade for retinal detachment related to choroiretinal coloboma improves the long-term anatomical outcome however no significant improvement in visual acuity was observed

Role of uterine artery doppler ultrasound in predicting preeclampsia in primigravida

Objective: To find the accuracy of uterine artery diastolic notching during the second trimester of pregnancy in predicting pre-eclampsia in primigravida patients

Study Design: Descriptive cross sectional study

Place and Duration of Study: Armed Forces Institute of Radiology and Imaging [AFIRI] Rawalpindi; six months duration from 30 Nov 2012 to 31 May 2013

Material and Methods: This study included 199 primigravida women with singleton pregnancy having diastolic notch in uterine arteries between 20 to 23 weeks of gestation. All patients were examined by both grey scale and doppler ultrasonography. Uterine arteries were evaluated with doppler near the point where they crossed the external iliac arteries. The patient was included in study if the presence of diastolic notch was demonstrated. Clinical follow up in gynae and obs department continued throughout the pregnancy to see if they developed preeclampsia. The data were recorded on a previously prepared proforma and analyzed with SPSS 21

Results: The accuracy of uterine artery doppler ultrasound in identifying women who later developed preeclampsia was 48.24%. The frequency of pre-eclampsia with bilateral notch was significantly high in the primigravid of younger age as compare to the primigravid of the older group [p=0.001]. The difference in frequency of developing pre-eclampsia with bilateral notch when compared among 20 to 21 week gestational age and 22 to 23 weeks gestational age was statistically insignificant

Conclusion: Uterine artery diastolic notching between 20 and 23 weeks of gestation is an important risk factor for developing pre-eclampsia. This doppler parameter should, therefore, be included in the risk evaluation for gestational hypertension

To compare the effectiveness of constraint induced movement therapy versus motor relearning programme to improve motor function of hemiplegic upper extremity after stroke

To compare the effectiveness of constraint induced movement therapy versus motor relearning programme to improve motor function of hemiplegic upper extremity after stroke. A sample of 42 patients was recruited from the Physiotherapy Department of IPM and R and Neurology OPD of Civil Hospital Karachi through non probability purposive sampling technique. Twenty one patients were placed to each experimental and control groups. Experimental group was treated with Constraint Induced Movement Therapy [CIMT] and control group was treated with motor relearning programme [MRP] for three consecutive weeks. Pre and post treatment measurements were determined by upper arm section of Motor Assessment Scale [MAS] and Self Care item of Functional Independence Measure [FIM] Scale. Intra group analysis showed statistically significant results [p-value<0.05] in all items of MAS in both groups. However, advanced hand activities item of MAS in MRP group showed insignificant result [p-value=0.059]. Self-care items of FIM Scale also showed significant result [p-value< 0.05] in both groups except dressing upper body item [p-value=0.059] in CIMT group and grooming and dressing upper body items [p-value=0.059 and 0.063] in MRP group showed insignificant p-values. CIMT group showed more significant improvement in motor function and self-care performance of hemiplegic upper extremity as compared to MRP group in patients with sub-acute stroke assessed by the MAS and FIM scales. Thus CIMT is proved to be more statistically significant and clinically effective intervention in comparison to motor relearning programme among the patients aged between 35-60 years. Further studies are needed to evaluate CIMT effects in acute and chronic post stroke population

Long term follow up of interferon treated chronic HCV patients in responders and non-responders

Interferon with ribavirin is the recommended treatment for chronic hepatitis C with a response rate ranging from 50-80% in different countries. Although sustained response is comparable to clinical cure, but whether interferon therapy slows down the disease process in non-responders and relapsers is not known. To determine the long term outcome of chronic HCV patients who have completed the interferon therapy and compare results between responders, relapsers and non-responders. Retrospective case record analysis of chronic hepatitis C patients who were treated with conventional interferon and ribavirin for 6 months during 1998 to 2002 and their follow up till 2011 were included. Depending upon the response they were divided into three groups i.e. responders, non responders and relapsers. A total of 175 patients were included. There were 126 [72%] males and 49 [28%] females, whose ages ranged from 11 to 70 years [mean 35.8 +/- 10.3]. After interferon therapy, 109 were sustained responders, 33 were relapsers and 33 non responders. Mean age of the responders [32.4 +/- 8.8 years] was significantly less as compared to non responders [40.4 +/- 12.0 years] and relapsers [42.4 +/- 8.0 years], [p < 0.05]. Responders had a much better follow up i.e four years as compared to non responders which was statistically significant[p <0.05]. During 10 years follow up, cirrhosis developed in 3 [2.8%] sustained responders, 6 [18.2%] non responders and 8 [24.2%] relapsers. During yearly followup, sustained responders had significantly lower mean ALT and AFP levels as compared to non responders and relapsers [p < 0.05] while non responders and relapsers had lower albumin levels as compared to the responders [p < 0.05]. Majority of the sustained responders had disease eradication, but non responders and relapsers should be followed for any evidence of cirrhosis

Isolation and Characterization of Halophilic Bacterial Strains from Saline Waters of Khewra Salt Mines on the Basis of 16S rRNA Gene Sequence.

Halophiles are salt loving microbes optimally growing at high concentrations of salt. Khewra salt mines of Pakistan provide extreme saline conditions where enormous halophilic microbial biota thrives. The present study aimed at isolation and molecular identification of bacterial strains from saline waters of Khewra salt mines. Using halophilic media, nine halophilic bacterial strains from saline water bodies were cultured and studied under optimized growth conditions (NaCl, pH and temperature). Bacterial growth at different NaCl concentrations was measured at 600nm wavelength, showing optimal growth at 1.5M NaCl. 769bp size 16S rRNA gene was amplified for molecular identification of bacterial strains. The amplified genes of the strains FA2.2 and FA3.3 were sequenced and their homology with other bacterial strains was analyzed. The results showed FA2.2 shared maximum homology with Bacillus anthracis strain while FA3.3 showed close resemblance with Staphylococcus saprophyticus subsp. bovis. Isolated halophilic bacterial strains possess potential for various biotechnological applications. They could be manipulated for synthesizing transgenic crops tolerating high salinity boosting the agricultural yield. Moreover extremozymes of these bacteria holds great industrial importance.

Changes in macular thickness and visual acuity after intravitreal bevacizumab injfection in patients with retinal vein occlusion

To evaluate the effect of singel Intravitreal Bevacizumab [Avastin] injection on visual acuity [VA] and central retinal thickness [CRT] in patients with macular edema secondary to branch retinal vein occlusion [BRVO] or central retinal vein occlusion [CRVO]. Prospective, non-randomized, interventional case series. This study was conducted at Al-Shifa Trust Eye Hospital Rawalpindi from March 2012 to February 2013. Twenty three patients with macular edema attributable to vein occlusion received intravitreal injection of Bevacizumab 1.25 mg. Nine patients had central retinal vein occlusion [CRVO] and 14 patients had branch retinal vein occlusion [BRVO]. Complete ophthalmic examination including best corrected visual acuity [BCVA] and optical coherence tomography [OCT] was done at base line and follow up visits. At base line mean visual acuity was Log MAR 0.73 and showed improvement to mean Log MAR 0.39 at 12 weeks after intravitreal Bevacizumab [IVB] injection. Mean CRT was 527 micro m at baseline that decreased to 274 micro m after 12 weeks of IVB treatment. Intravitreal Bevacizumab appears to result in significant short term improvement of VA and macular edema secondary to vein occlusion