SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.

Analytical assessment of clinical sensitivity and specificities of pharmaceutical rapid SARS-CoV-2 detection nasopharyngeal swab testing kits in Pakistan.

Despite of the global unity against COVID-19 pandemic, the threat of SARS-CoV-2 variants on the lives of human being is still not over. SARS-CoV-2 pandemic has urged the need of rapid viral detection at earliest. To cope with gradually expanding scenario of SARS-CoV-2, accurate diagnosis is extremely crucial factor which should be noticed by international health organizations. Limited research followed by sporadic marketing of SARS-CoV-2 rapid pharmaceutical detection kits raises critical questions against quality assurance and quality control measures. Herein we aimed to interrogate effectivity and specificity analysis of SARS-CoV-2 pharmaceutical rapid detection kits (nasopharyngeal swab based) using conventional gold standard triple target real-time polymerase chain reaction (USFDA approved). A cross-sectional study was conducted over 1500 suspected SARS-CoV-2 patients. 100 real time-PCR confirmed patients were evaluated for pharmaceutical RDT kits based upon nasopharyngeal swab based kits. The SARS-CoV-2 nasopharyngeal swab based rapid diagnostic kit (NSP RDTs) analysis showed 78% reactivity. Among real time PCR confirmed negative subjects, 49.3% represented false positivity. The positive predictive analysis revealed 67.82%, while negative predictive values were 64.40%. The NSP RDTs showed limited sensitivities and specificities as compared to gold standard real time PCR. Valid and authentic detection of SARS-CoV-2 is deemed necessary for accurate COVID-19 surveillance across the globe. Current study highlights the potential consequences of inadequate detection of SARS-CoV-2 and emerging novel mutants, compromising vaccine preventable diseases. Current study emphasizes need to wake higher authorities including strategic organizations for designing adequate measures to prevent future SARS-CoV-2 epidemics.

Hepatitis C virus associated ALT, AST, GGT, Bili T, HB, HBA1C, CREAT, PT, aPPT, AFP, CEA, CA 125, CA 19-9, iPTH biomarkers, computed tomography and HCV burden of disease during pre COVID-19 era (2018-2019) and post COVID-19 era (2020-2022) in Pakistan.

The national burden of HCV has significantly mounted over the period of last few decades placing Pakistan at the worst placement of second largest burden of HCV globally. Herein for the first time from Pakistan, we examined clinical correlation of potential biomarkers with HCV. Nation-wide study was conducted on 13,348 suspected HCV patients during 2018-2022. During pre-COVID-19 era of 2018-2019, prevalence of HCV remained 30%. During 2018, among HCV positive patients, 91% of ALT, 63% of AST, 67% of GGT, 28% of Bili T, 62% of HB, 15% of HBA1C, 25% of CREAT, 15% of PT, 15% of aPTT and 64% of AFP were abnormal. During 2019, among HCV infected 74.47% of ALT, 63.54% of AST, 70.24% of GGT, 24.71% of Bili T, 8.77% of HB and 75% of AFP were raised. CT/CAT scan revealed 4.65% liver complications (mild 13.04%, moderate 30.43% and severe 56.52%). During 2020, HCV prevalence remained 25%. 65.17% of ALT, 64.20% of AST, 68.75% of GGT, 31.25% of Bili T, 20.97% of HB, 4.65% of CREAT and 73.68% of AFP levels were raised. CAT analysis revealed liver complications among 4.41% (14.81% mild, 40.74% moderate, and 44.44% sever). 85.71% of participants diabetes was out of control. During 2021, HCV prevalence remained 27.1%. ALT (73.86%), AST (50.6%), GGT (67.95%), Bili T (28.21%), HB (20%), CREAT (5.8%) and AFP (82.14%) levels were abnormal. During 2022, the levels of ALT (56.06%), AST (56.36%), GGT (56.6%), Bili T (19.23%), HB (43.48%), HBA1C (14.81), CREAT (18.92%), AFP (93.75%) were abnormal. CAT analysis revealed 7.46% liver complications (25% mild, 30.36% moderate, and 42.86% sever). During 2021-2022, 83.33% of subject's diabetes was not controlled.

Revised guidelines on management of antenatal hydronephrosis.

Widespread antenatal screening has resulted in increased detection of anomalies of the kidneys and urinary tract. The present guidelines update the recommendations published in 2000. Antenatal hydronephrosis (ANH) is transient and resolves by the third trimester in almost one-half cases. The presence of oligohydramnios and additional renal or extrarenal anomalies suggests significant pathology. All patients with ANH should undergo postnatal ultrasonography; the intensity of subsequent evaluation depends on anteroposterior diameter (APD) of the renal pelvis and/or Society for Fetal Urology (SFU) grading. Patients with postnatal APD exceeding 10 mm and/or SFU grade 3-4 should be screened for upper or lower urinary tract obstruction and vesicoureteric reflux (VUR). Infants with VUR should receive antibiotic prophylaxis through the first year of life, and their parents counseled regarding the risk of urinary tract infections. The management of patients with pelviureteric junction or vesicoureteric junction obstruction depends on clinical features and results of sequential ultrasonography and radionuclide renography. Surgery is considered in patients with increasing renal pelvic APD and/or an obstructed renogram with differential renal function <35-40% or its subsequent decline. Further studies are necessary to clarify the role of prenatal intervention, frequency of follow-up investigations and indications for surgery in these patients.

Clinical and biomarker profile of trauma-induced secondary cardiac injury.

BACKGROUND: Secondary cardiac injury has been demonstrated in critical illness and is associated with worse outcomes. The aim of this study was to establish the existence of trauma-induced secondary cardiac injury, and investigate its impact on outcomes in injured patients. METHODS: Injured adult patients eligible for enrolment in the Activation of Coagulation and Inflammation in Trauma 2 study, and admitted to the intensive care unit between January 2008 and January 2010, were selected retrospectively for the study. Markers of cardiac injury (brain natriuretic peptide (BNP), heart-type fatty acid binding protein (H-FABP) and troponin I) were measured on admission, and after 24 and 72 h in blood samples from injured patients. Individual records were reviewed for adverse cardiac events and death. RESULTS: During the study period, 135 patients were enrolled (106 male, 78·5 per cent) with a median age of 40 (range 16-89) years. Eighteen patients (13·3 per cent) had an adverse cardiac event during admission and these events were not associated with direct thoracic injury. The in-hospital mortality rate was higher among the adverse cardiac event cohort: 44 per cent (8 of 18) versus 17·1 per cent (20 of 117) (P = 0·008). Raised levels of H-FABP and BNP at 0, 24 and 72 h, and troponin I at 24 and 72 h, were associated with increased adverse cardiac events. BNP levels were higher in non-survivors on admission (median 550 versus 403 fmol/ml; P = 0·022), after 24 h (794 versus 567 fmol/ml; P = 0·033) and after 72 h (1043 versus 753 fmol/ml; P = 0·036), as were admission troponin I levels. CONCLUSION: Clinical and cardiac biomarker characteristics support the existence of trauma-induced secondary cardiac injury, which is associated with death, and unrelated to direct thoracic injury.

Case fatality rates for South Asian and Caucasian patients show no difference 2.5 years after percutaneous coronary intervention.

OBJECTIVE: To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates. DESIGN: Retrospective cohort study. SETTING: A cardiology referral centre in east London. PATIENTS: 9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian. MAIN OUTCOME MEASURES: In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5 years (range 1.5-3.6 years). RESULTS: South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13 years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan-Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23). CONCLUSION: In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.

Telemedicine for multidisciplinary lung cancer meetings.

According to recent UK guidelines on the management of lung cancer, all cases should be reviewed prospectively by a lung cancer multidisciplinary team (MDT) and a thoracic surgeon should be readily available to liaise with the MDT. However, there is a shortage of thoracic surgeons in the UK. Over a one-year period, 28 MDT meetings were held at a district general hospital in Southend, at which 62 patients were presented to a tertiary cardiothoracic centre in London, 80 km away, via ISDN videoconferencing at 384 kbit/s. The annual resection rate increased by 30% following the introduction of the telemedicine MDTmeetings, and the mean time from first being seen in the clinic to surgery was reduced from 69 to 54 days.We estimate that the telemedicine meetings saved over three working weeks of thoracic surgical time during the year.

The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision.

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared. Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction. All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity. This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.

Do oral flora colonize the nasal floor of patients with oronasal fistulae?

OBJECTIVE: To determine if oral bacteria colonize the cleft nasal floor in patients with unilateral oronasal fistula when compared with the unaffected nasal floor and whether the results obtained would be of benefit in assessing oronasal fistulae in the clinic. DESIGN: Prospective study of 26 patients with cleft palate and unilateral oronasal fistula. Microbiological culture swabs were taken from the mouth and nasal floors of patients. The unaffected nasal floor was used as a control. Bacterial isolates were identified and compared in the laboratory by a senior microbiologist. MAIN OUTCOMES MEASURE: A significant growth of oral bacteria from the cleft nasal floor when compared with the unaffected nasal floor. RESULTS: Four patients were excluded because no growth was found on any culture plate. In the remaining 22 cases, a light growth of oral flora was found in the cleft nasal floor in only 3 patients. No statistical correlation between culture of oral bacteria and the cleft nasal floor could be found (p =.12). CONCLUSIONS: The relative lack of colonization of the cleft nasal floor by oral bacteria may reflect poor transmission of bacteria through the fistula, competition with commensal nasal flora, or an inability of oral bacteria to survive in a saliva-depleted area. The investigation is not helpful in the assessment of oronasal fistulae in the clinic.

Cleft lip and palate management by U.K. consultant oral and maxillofacial surgeons: a national survey.

OBJECTIVE: Following the report of the Clinical Standards Advisory Group (CSAG), a national survey of U.K. consultant oral and maxillofacial surgeons was performed to determine the current cleft lip and palate practice of this group prior to the implementation of proposed radical changes in the delivery of cleft services. The views of these surgeons regarding the proposed changes was also sought. DESIGN: An anonymous postal questionnaire sent to all 266 consultants in the U.K., which requested information on the practice of cleft surgery during a defined 1-year period (March 1997 through February 1998). It included the numbers and types of procedures performed, the involvement of multidisciplinary care, research and audit activity, and questions regarding the implementation of CSAG. RESULTS: One hundred ninety-one replies (72% response rate). Seventy-three surgeons were actively involved with mainly secondary cleft surgery. A varied number and range of procedures were undertaken, with most surgeons performing less than five of each procedure per year. Audit and research activity was 26%. The majority of both noncleft and cleft surgeons agreed with proposals made by CSAG (except for cleft osteotomy procedures). CONCLUSIONS: In the U.K. at present, there are many oral and maxillofacial surgeons performing mainly secondary cleft surgery; overall, the number of procedures performed by these surgeons per year is small. Intraspecialty referral is suggested to further improve patient outcome.

Use of cold medications for upper respiratory tract infections in children.

Prescribing practices in the treatment of upper respiratory tract infections (URTI) in children were studied, with particular emphasis on overuse of antibiotics, combination cold medications, and off-label use of medicines in children. Prescriptions with the diagnosis of URTI were studied over a period of 5 months in a general pediatric clinic. Out of 224 prescriptions scrutinized, a cold medication was prescribed in 88.4% of cases and 50.9% prescriptions contained a combination preparation. Antihistamines (50.9%), alpha-adrenoceptor agonist decongestants (50.0%) and opioid anti-tussives (24.5%) were the common ingredients of cold medications. Antihistamines (35.7%) were also used alone. Of the children 18.2% were receiving a drug contraindicated or not recommended in their age group. Antibiotics were prescribed in only 8.5% of cases, and for appropriate indications, reflecting a more restrained use of antibiotics.

Concomitant off-pump myocardial revascularization and pheochromocytoma resection.

Surgical management of patients with coexisting ischemic heart disease and pheochromocytoma remains challenging. We present one such case in which hybrid myocardial revascularization (angioplasty with stenting and off-pump coronary artery bypass grafting) and resection of pheochromocytoma were undertaken. Unusual features included simultaneous coronary artery surgery and tumor resection and, in particular, coronary artery surgery being performed without cardiopulmonary bypass.

Effect of oral magnesium supplementation on blood pressure, platelet aggregation and calcium handling in deoxycorticosterone acetate induced hypertension in rats.

OBJECTIVE: To study the effect of oral magnesium supplementation on blood pressure, platelet aggregation and platelet calcium handling in deoxycorticosterone acetate (DOCA)-induced hypertension in rats. DESIGN AND METHODS: Rats were divided into four groups of 20 each. Drug treatments were given for a 6-week period. Control rats were vehicle treated. In the second group, DOCA, 15 mg/kg, was injected subcutaneously twice weekly with 1% NaCl used instead of drinking water. The third group was given magnesium oxide (MgO), 1 g/kg daily, orally by gavage. The fourth group was given MgO along with DOCA and 1% NaCl. Blood pressure and heart rate were measured weekly. Platelet aggregation, intracellular calcium, calcium uptake and calcium efflux studies were performed at the end of sixth week. Serum magnesium concentration, plasma levels of reactive nitrogen intermediates (RNI) and citrulline were also measured RESULTS: There was a significant rise in blood pressure in the DOCA-treated rats. Magnesium prevented the gradual rise in blood pressure when given along with DOCA, but had no effect in normotensive rats. Heart rate did not show any significant change. Platelet aggregation was significantly reduced in all the treatment groups compared to the control group. DOCA treatment produced a significant increase in the intracellular calcium concentration as well as the calcium uptake compared to the control group. Magnesium supplementation inhibited the increased intracellular calcium concentration and calcium uptake in DOCA-treated rats. RNI and citrulline levels were elevated in all the treatment groups. Serum magnesium levels were significantly higher in the magnesium-treated and DOCA plus magnesium-treated rats. CONCLUSIONS: Magnesium supplementation prevents blood pressure elevation in DOCA hypertensive rats. These effects are associated with inhibition of platelet calcium uptake and decreased intracellular free calcium concentration.

Aplasia cutis congenita associated with a lipoma.

Aplasia cutis congenita is a condition that can present with a wide variety of symptoms and many attempts have been made to classify it comprehensively. This report presents the first case of a child with aplasia cutis congenita confirmed on histology with an associated lipoma or lipomatosis directly underlying it. It exemplifies the difficulty in diagnosing and treating this rare condition.

Adverse drug reactions among inpatients in a north Indian referral hospital.

BACKGROUND: Monitoring spontaneous adverse drug reactions is one of the epidemiological methods for assessing the safety of drugs in a hospital setting. METHODS: Data on adverse drug reactions (ADRs) were collected over a 3-year period among inpatients in a north Indian referral hospital using the spontaneous ADR monitoring system. RESULTS: A total of 317 ADRs were reported. Cutaneous reactions (38.8%) and gastrointestinal disturbances (28.4%) made up a large proportion of reported ADRs. Antimicrobial agents, including those used for antituberculosis therapy, were responsible for 47.3% of the events. Radiocontrast dyes, and antineoplastic and psychoactive agents were the other important drugs causing ADRs. No age- or sex-related differences were found in the overall rate of ADRs, though toxic epidermal necrolysis was more frequent in the elderly. CONCLUSION: The pattern of ADRs and drugs involved were largely similar to those reported in the western literature.