Covid-19 related isolation and risk of post-traumatic stress disorder in patients presenting to tele-clinics at a private tertiary care hospital in Karachi.

The objective of this study was to assess the psychological impact of isolation on individuals with Covid-19 and determine the experiences of people in isolation. All adults with Covid-19 who reported to the infectious disease tele-clinic were included in the study; participants were sent the survey form via email. The email was sent to 146 people and 47 responses were received. IES-R questionnaire was submitted to all individuals on Day 7 of quarantine, along with a qualitative questionnaire. The mean score on IES-R for all the respondents was 18.77. Out of 47 participants, for 6 (12.8%) PTSD was a clinical concern, 3 (6.4%) participants had a probable diagnosis of PTSD, and 6 (12.8%) participants scored high enough to suppress immune function. The majority of participants reported stress due to confinement in an isolated space and interruption in daily routine, specifically work-related routine. Praying, meditation, and having social support helped the participants cope with the isolation.

Advancing Cardiovascular Risk Assessment with Artificial Intelligence: Opportunities and Implications in North Carolina.

Cardiovascular disease mortality is increasing in North Carolina with persistent inequality by race, income, and location. Artificial intelligence (AI) can repurpose the widely available electrocardiogram (ECG) for enhanced assessment of cardiac dysfunction. By identifying accelerated cardiac aging from the ECG, AI offers novel insights into risk assessment and prevention.

A large abdominal cyst as a manifestation of pelviureteric junction obstruction in a neonate.

Intraabdominal cystic lesions diagnosed during antenatal period are uncommon. They are found to have varying origins, with renal tract being the most common site. Rarely, a large unilateral cystic lesion of renal origin is caused by Pelviureteric junction obstruction, crossing the midline, leading to compression of the contralateral kidney. We present a case of a neonate who was diagnosed with a large abdominal cyst in the antenatal period. The cyst persisted and crossed the midline causing hydronephrosis on the contralateral side. This is an unusual presentation of a commonly occurring condition, usually such large cyst at birth origins from alimentary tract rather renal system. It is important to understand unusual presentations of intraabdominal lesions and the associated pathology. It is mandatory to rule out renal obstruction, if there is any decompression of renal function, it is mandatory to save renal function till the time of definitive surgery.

Impact of Postoperative Antibiotic Prophylaxis on Surgical Site Infections Rates After Mastectomy with Drains but Without Immediate Reconstruction: A Multicenter, Double-Blinded, Randomized Control Superiority Trial.

BACKGROUND: There is no consensus on the use of postoperative antibiotic prophylaxis (PAP) after mastectomy with indwelling drains. We explored the utility of continued PAP in reducing surgical site infection (SSI) rates after mastectomy without immediate reconstruction and with indwelling drains. PATIENTS AND METHODS: A multicenter, two-armed, randomized control superiority trial was conducted in Pakistan. We enrolled all consenting adult patients undergoing mastectomy without immediate reconstruction. All patients received a single preoperative dose of cephalexin within 60 min of incision, and postoperatively were randomized to receive either continued PAP using cephalexin (intervention) or a placebo (control) for the duration of indwelling, closed-suction drains. The primary outcome was the development of SSI within 30 days and 90 days postoperatively. Secondary outcomes included study-drug-associated adverse events. Intention-to-treat analysis was performed using multivariable Cox regression. RESULTS: A total of 369 patients, 180 (48.8%) in the intervention group and 189 (51.2%) in the control group, were included in the final analysis. Overall cumulative SSI rates were 3.5% at 30 days and 4.6% at 90 days postoperatively. PAP was not associated with SSI reduction at 30 (hazard ratio, HR 1.666 [95% confidence interval CI 0.515-5.385]) or 90 (1.575 [0.558-4.448]) days postoperatively, or with study-drug-associated adverse effects (0.529 [0.196-1.428]). CONCLUSIONS: Continuing antibiotic prophylaxis for the duration of indwelling drains after mastectomy without immediate reconstruction offers no additional benefit in terms of SSI reduction. There is a need to update existing guidelines to provide clearer recommendations regarding use of postoperative antibiotic prophylaxis after mastectomy in the setting of indwelling drains.

Humoral and T cell responses to SARS-CoV-2 reveal insights into immunity during the early pandemic period in Pakistan.

BACKGROUND: Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a healthy control group (HG) as compared with COVID-19 cases and individuals from the pre-pandemic period (PP). METHODS: HG and COVID-19 participants were recruited between October 2020 and May 2021. Pre-pandemic sera was collected before 2018. IgG antibodies against Spike and its Receptor Binding Domain (RBD) were determined by ELISA. Virus neutralization activity was determined using a PCR-based micro-neutralization assay. T cell - IFN-γ activation was assessed by ELISpot. RESULTS: Overall, the magnitude of anti-Spike IgG antibody levels as well as seropositivity was greatest in COVID-19 cases (90%) as compared with HG (39.8%) and PP (12.2%). During the study period, Pakistan experienced three COVID-19 waves. We observed that IgG seropositivity to Spike in HG increased from 10.3 to 83.5% during the study, whilst seropositivity to RBD increased from 7.5 to 33.3%. IgG antibodies to Spike and RBD were correlated positively in all three study groups. Virus neutralizing activity was identified in sera of COVID-19, HG and PP. Spike reactive T cells were present in COVID-19, HG and PP groups. Individuals with reactive T cells included those with and without IgG antibodies to Spike. CONCLUSIONS: Antibody and T cell responses to Spike protein in individuals from the pre-pandemic period suggest prior immunity against SARS-CoV-2, most likely from cross-reactive responses. The rising seroprevalence observed in healthy individuals through the pandemic without known COVID-19 may be due to the activation of adaptive immunity from cross-reactive memory B and T cells. This may explain the more favourable COVID-19 outcomes observed in this population.

Comparison of risk factors and outcome of patients with and without COVID-19-associated pulmonary aspergillosis from Pakistan: A case-control study.

BACKGROUND: Early identification of COVID-19-associated pulmonary aspergillosis (CAPA) is particularly challenging in low- middle-income countries where diagnostic capabilities are limited, and risk factors for CAPA have not been identified. It is also essential to recognise CAPA patients who are likely to have a poorer outcome to decide on aggressive management approaches. Therefore, this study aimed to identify risk factors and outcomes for CAPA among admitted moderate to critical COVID-19 patients at our centre in Pakistan. METHODS: An unmatched case-control study with ratio of 1:2 was conducted on hospitalised adult patients with COVID-19 from March 2020-July 2021. Cases were defined according to European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Controls were defined as patients hospitalised with moderate, severe or critical COVID-19 without CAPA. RESULTS: A total of 100 CAPA cases (27 probable CAPA; 73 possible CAPA) were compared with 237 controls. Critical disease at presentation (aOR 5.04; 95% CI 2.18-11.63), age ≥ 60 years (aOR 2.00; 95% CI 1.20-3.35) and underlying co-morbid of chronic kidney disease (CKD) (aOR 3.78; 95% CI 1.57-9.08) were identified as risk factors for CAPA. Patients with CAPA had a significantly greater proportion of complications and longer length of hospital stay (p-value < .001). Mortality was higher in patients with CAPA (48%) as compared to those without CAPA (13.5%) [OR = 6.36(95% CI 3.6-11)]. CONCLUSIONS: CAPA was significantly associated with advanced age, CKD and critical illness at presentation, along with a greater frequency of complications and higher mortality.

Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study.

OBJECTIVE: Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac. METHODS: Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N'-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits. RESULTS: Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends. CONCLUSION: The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.

Synthesis of novel combinatorial drug delivery system (nCDDS) for co-delivery of 5-fluorouracil and leucovorin calcium for colon targeting and controlled drug release.

OBJECTIVE: Purpose of the current study was to improve the oral effectiveness of 5-fluorouracil (5-FU) by developing novel controlled, combinatorial drug delivery system (nCDDS) for co-delivery of 5-FU and leucovorin calcium (LC) for colon targeting. SIGNIFICANCE: On the basis of results obtained, novel controlled, combinatorial drug delivery system could be an effective strategy for the colon targeting of 5-FU and LC. METHODS: Free radical polymerization method was tuned and used to fabricate this nCDDS. The nCDDS is synthesized in two steps, first synthesis of 5-FU/LC calcium loaded nanogels and second, pre-synthesized 5-FU and LC loaded nanogels were dispersed in pectin based polymerized matrix hard gel. The nanogels and nCDDS gels were characterized for network structure, thermal stability, and surface morphology. Swelling and in vitro release studies were carried out at different pH 1.2 and 7.4 both for naive nanogels and combined matrix gels. In vivo study of combinatorial gel was performed on rabbits by using HPLC method to estimate plasma drug concentration and pharmacokinetics parameters. RESULTS: Structure and thermal analysis confirmed the formation of stable polymeric network. SEM of nanogels and combinatorial gels showed that the spongy and rough edges particles and uniformly distributed in the combinatorial gel. The prepared nCDDS showed excellent water loving capacity and pH responsiveness. Combinatorial gel showed excellent characteristic for colonic delivery of drugs, which were confirmed by various in vitro and in vivo characterizations. Acute oral toxicity study of combinatorial gel confirmed the biocompatible and nontoxic characteristics of developed formulation. CONCLUSION: Conclusively, it can be found that nCDDS showed excellent properties regarding drug targeting in a controllable manner as compared to naive PEGylated nanogels.

Synthesis of PEG-4000-co-poly (AMPS) nanogels by cross-linking polymerization as highly responsive networks for enhancement in meloxicam solubility.

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and in vitro dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic®). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system.

Comparison of risk factors and outcomes of Candida auris candidemia with non-Candida auris candidemia: A retrospective study from Pakistan.

Candida auris has emerged as a nosocomial multi-drug resistant pathogen. This study aimed to compare the risk factors and outcomes of C. auris candidemia patients with non-C. auris candidemia, at a single center in Pakistan. A retrospective study compared 38 C. auris with 101 non-C. auris (36 C. albicans, 38 C. tropicalis, and 27 C. parapsilosis) candidemia patients between September 2014 and March 2017 at the Aga Khan University Hospital, Pakistan. Demographics, clinical history, management and outcomes were studied. Prior history of surgery (adjusted odds ratio [aOR] 4.9, 95% confidence interval [CI]: 1.4-17.5), antifungals exposure (aOR 38.3, 95% CI: 4.1-356) and prior MDR bacteria isolation (aOR 5.09, 95% CI: 1.6-15.9) were associated with C. auris candidemia. On survival analysis both groups of patients had similar outcome in terms of mortality (62.6% vs. 52.54%, hazard ratio [HR] 1.45, 95% CI: 0.84-2.4, P-value = .17) and microbiological failure rates (42.3% vs. 32.2%, HR 0.65, 95% CI: 0.35-1.2, P-value = .17) however, C. auris patients had a higher mean hospital stay (36.32 days vs. 14.8 days, P-value = <.001) and higher >15-day in-hospital stay from positive culture (HR 2.68, 95% CI: 1.1-6.3, P-value = .025). Antifungal susceptibility was different, with C. auris more often resistant to voriconazole (29.6% vs. 0%) and amphotericin (3.7 vs. 0%); though no echinocandin resistance was detected in either group. As opposed to other Candida species, C. auris candidemia occurred after nosocomial exposure, and its source was most commonly an indwelling line. Although these patients had a higher in-hospital stay, but there was no excess mortality when compared to other Candida species.

The emergence of an unassigned complex recombinant form in a Pakistani HIV-infected individual.

In Pakistan, the HIV situation has gone from an outbreak to a concentrated epidemic, and the virus has now crossed into the low-risk population. In addition, several new HIV outbreaks have occurred in different parts of the country. HIV-1 subtype A has been the major epidemic subtype in Pakistan; however, as the epidemic has grown, the emergence of several new subtypes and recombinant forms has been observed. Here, we present the first case and genetic analysis of an unassigned, complex recombinant form in a Pakistani HIV-infected individual with virological failure. Genetic analysis of the sequence indicated that this recombinant form is multi-drug resistant, harboring drug resistance mutations against more than one class of antiretroviral drugs.

COVID-19-associated pulmonary aspergillosis (CAPA) in patients admitted with severe COVID-19 pneumonia: An observational study from Pakistan.

BACKGROUND: Invasive aspergillosis is a well-known complication of severe influenza pneumonia with acute respiratory distress syndrome (ARDS). However, recent studies are reporting emergence of aspergillosis in severe COVID-19 pneumonia, named as COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: A retrospective observational study was conducted in patients with severe COVID-19 pneumonia from February 2020 to April 2020. Patients ≥18 years of age with clinical features and abnormal chest imaging with confirmed COVID-19 by RT-PCR for SARS-CoV-2 were included. CAPA was diagnosed based on clinical parameters, radiological findings and mycological data. Data were recorded on a structured proforma, and descriptive analysis was performed using Stata ver 12.1. RESULTS: A total of 147 patients with confirmed COVID-19 and 23 (15.6%) patients requiring ICU admission were identified. Aspergillus species were isolated from tracheal aspirates of nine (39.1%) patients, and of these, five patients (21.7%) were diagnosed with CAPA and four (17.4%) had Aspergillus colonisation. The mean age of patients with CAPA was 69 years (Median age: 71, IQR: 24, Range: 51-85), and 3/5 patients were male. The most frequent co-morbid was diabetes mellitus (4/5). The overall fatality rate of COVID-19 patients with aspergillosis was 44% (4/9). The cause of death was ARDS in all three patients with CAPA, and the median length of stay was 16 days (IQR: 10; Range 6-35 days). CONCLUSION: This study highlights the need for comparative studies to establish whether there is an association of aspergillosis and COVID-19 and the need for screening for fungal infections in severe COVID-19 patients with certain risk factors.

Hyperthermia and protein homeostasis: Cytoprotection and cell death.

Protein homeostasis or proteostasis, the correct balance between production and degradation of proteins, is an essential pillar for proper cellular function. Among the several cellular mechanisms that disrupt homeostatic conditions in cancer cells, hyperthermia (HT) has shown promising anti-tumor effects. However, cancer cells are also capable of thermoresistance. Indeed, HT-induced protein denaturation and aggregation results in the up regulation of heat shock proteins, a group of molecular chaperones with cytoprotective and anti-apoptotic properties via stress-inducible transcription factor, heat shock factor 1(HSF1). Heat shock proteins assist in the refolding of misfolded proteins and aids in their elimination if they become irreversibly damaged by various stressors. Furthermore, HSF1 also initiates the unfolded protein response in the endoplasmic reticulum (ER) to assist in the protein folding capacity of ER and also promotes the translation of pro-survival proteins' mRNA such as activating transcription factor 4 (ATF 4). Moreover, HT associated induction of microRNAs is also involved in thermal resistance of cancer cells via up-regulation of anti-apoptotic Bcl-2 proteins and down regulation of pro-apoptotic Bax and caspase 3 activities. Another cellular protection in response to stressors is Autophagy, which is regulated by the Mammalian target of rapamycin (mTOR) protein. Kinase activity in mTOR phosphorylates HSF1 and promotes its nuclear translocation for heat shock protein synthesis. Over-expression of heat shock proteins are reported to up-regulate Beclin-1, an autophagy initiator. Moreover, HT-induced reactive oxygen species (ROS) generation is sensitized by transcription factor NF-E2 related factor 2 (Nrf2) and activates the cellular expression of antioxidants and autophagy gene. Furthermore, ROS also potentiates autophagy via activation of Beclin-1. Inhibition of thermotolerance can potentiate HT-induced apoptosis. Here, we outlined that heat stress alters cellular proteins which activates cellular homeostatic processes to promote cell survival and make cancer cells thermotolerant.

In vitro and in vivo anti-Helicobacter pylori activity of selected medicinal plants employed for the management of gastrointestinal disorders.

Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria chamomilla L. and Foeniculum vulgare Mill. were selected for their in vitro and in vivo evaluation of anti-Helicobacter pylori activity. In vitro evaluation was performed by using disk diffusion method and minimum inhibitory concentrations were noted while rat models were selected for in vivo activity against four Helicobacter pylori strains isolated form gastric mucosa. Mentha piperita showed largest zone of inhibition with 9 mm diameter among all other extracts. All the plants showed promising anti-Helicobacter pylori activity against four isolates and a reference strain at concentrations of 125, 250, 500 and 1000 µg/ml in comparison with Amoxicillin 1 µg/ml but least MIC was exhibited by Mentha piperita followed by in vivo testing where it competed Amoxicillin at 1000 mg/kg by achieving 80% eradication of Helicobacter pylori in mucosa of infected rats justified by histological examination of stomach. It was concluded that medicinal plants possess strong anti-Helicobacter pylori activity and can be considered a potential source of safe and effective alternative regimens for the eradication of Helicobacter pylori.

Clinical spectrum and factors impacting outcome of Candida auris: a single center study from Pakistan.

BACKGROUND: An outbreak of Candida auris began globally in 2014 including Pakistan and since then it has emerged as a nosocomial multi-drug resistant pathogen. The aim of this study was to assess the clinical spectrum and outcome of patients, from a single center in Pakistan, in whom C. auris was isolated. METHODS: A retrospective study was conducted on 92 patients; ≥16 years with at least one culture positive for C. auris, at the Aga Khan University Hospital Karachi, Pakistan from Sept 2014-Mar 2017.Demographics, clinical history, management and outcome were studied. A logistic regression model was used to identify the risk factors for mortality. RESULTS: We identified 92 patients with C. auris (193 isolates), of whom 52.2% were males. Mean age was 54.14 ± 20.4 years. Positive cultures were obtained after a median hospital stay of 14 days. Most patients had a history of surgery (57.6%), antibiotic use (95.6%), ICU stay (44.6%), indwelling lines (88.04%) and isolation of another multi-resistant organism (52.2%).Most patients were symptomatic (70.7%). Amongst these, 38 had candidemia while 27 had non-candidemia infections. Sites of infection included central lines (35), urinary tract (19), peritonitis (4), nosocomial ventriculitis (1), empyema (1), fungal keratitis (1) otitis externa (1) and surgical site (1). Fluconazole resistance was 100% while 28.5 and 7.9% were Voriconazole and Amphotericin resistant respectively. Overall crude mortality was 42.4% while 14-day mortality was 31.5%. Both infected and colonized cases shared similar mortality (46.2% vs 33.3%; p-value = 0.25). Among infected cases mortality was high in candidemia compared to non-candidemia (60.5% vs 25.9%) in which deaths related to C. auris were 34.2% vs 22.2% respectively. On multivariate analysis candidemia (AOR 4.2, 95% CI: 1.09-16.49; p-value = 0.037) was associated with greater mortality with source control being the only protective factor for mortality (AOR 0.22, 95% CI: 0.05-0.92; p-value0.038] while ICU stay, rapidity of blood culture clearance, DM, malignancy and MDR co-infection had no impact. CONCLUSION: Patients with C.auris from a single center in Pakistan have a wide clinical spectrum with line associated infection being the predominant site of infection. Candidemia leads to high mortality while source control improves outcome.

Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy.

We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA. Thirty boys with DMD (median age 10.0 years (6.1, 16.8)) were compared with 30 controls. SH in DMD was 3.3 cm lower (95% CI - 6.1, - 0.66; p = 0.016). LL in DMD was 7.3 cm lower (95% CI - 11.2, - 3.4; p < 0.0001). SH:LL of boys with DMD was higher by 0.08 (95% CI 0.04, 0.12; p < 0.0001). Femur length in DMD was 2.4 cm lower (95% CI - 4.6, - 0.12; p = 0.04), whereas tibial length in DMD was 4.8 cm lower (95% CI - 6.7, - 2.9; p < 0.0001). SH:LL was not associated with duration of glucocorticoid use (SH:LL ß = 0.003, 95% CI - 0.01 to 0.002, p = 0.72).Conclusion: Glucocorticoid-treated boys with DMD exhibit skeletal disproportion with relatively shorter leg length and more marked reduction of distal long bones. As glucocorticoid excess is not associated with such disproportion, our findings raise the possibility of an intrinsic disorder of growth in DMD. What is Known • Severe growth impairment and short stature are commonly observed in boys with Duchenne muscular dystrophy (DMD), especially those treated with long-term glucocorticoids (GC). • In other groups of children with chronic conditions and/or disorders of puberty, skeletal disproportion with lower spinal length has been reported. What is New • Growth impairment in GC-treated boys with DMD was associated with skeletal disproportion in relation to age, with lower limbs and distal long bones affected to a greater degree.

The Role of International Databases in Understanding the Aetiology and Consequences of Differences/Disorders of Sex Development.

The International Disorders of Sex Development (I-DSD) and International Congenital AdrenalHyperplasia registry (I-CAH) Registries were originally developed over 10 years ago and have since supported several strands of research and led to approximately 20 peer-reviewed publications. In addition to acting as an indispensable tool for monitoring clinical and patient-centered outcomes for improving clinical practice, the registries can support a wide nature of primary and secondary research and can also act as a platform for pharmacovigilance, given their ability to collect real world patient data within a secure, ethics approved virtual research environment. The challenge for the future is to ensure that the research community continues to use the registries to improve our understanding of Disorders of Sex Development (DSD).

pH/Thermo-Dual Responsive Tunable In Situ Cross-Linkable Depot Injectable Hydrogels Based on Poly(N-Isopropylacrylamide)/Carboxymethyl Chitosan with Potential of Controlled Localized and Systemic Drug Delivery.

In the current study, cytocompatible in situ cross-linkable pH/thermo-dual responsive injectable hydrogels were prepared based on poly(N-isopropylacrylamide) and carboxymethyl chitosan, i.e., poly(CMCS-g-NIPAAm). The prepared formulations were aimed to be used as drug depot of 5-fluorouracil (5-FU) after subcutaneous administration in vivo. The phase transition from sol-gel state under physiologic temperature range was analyzed and confirmed by tube titling and optical transmittance measurements. The viscoelastic properties of gel formulations were confirmed by rheology determination via time sweep, temperature, and continuous ramp test. Oscillatory swelling cycles confirmed temperature effect and structural changes. pH and temperature sensitivity of dual responsive gels were analyzed at different pH and temperature programs. In vitro drug release profile displayed that developed formulations have the highest release in acidic pH at 25°C. The safety of blank gel formulations was evaluated against L929 cell lines via MTT assay and confirmed cytocompatibility with no detectable toxicity. In vitro cytotoxic potential of drug-loaded gels against HeLa and MCF-7 cancer cell lines confirmed that 5-FU has controlled cytotoxic potential in depot form in comparison to free 5-FU solution. The IC50 values for free 5-FU (21 ± 05 µg/ml and 18 ± 66 µg/ml) were found higher in comparison to the loaded form. The copolymer structure formation was confirmed by NMR and FTIR spectroscopic analysis. TG and DSC analysis proved the thermal stability and phase transition temperatures of pure and copolymer samples, while SEM analysis showed the porous nature of in situ formed hydrogels. It was concluded from the results that the developed formulations have pH/temperature sensitivity with potential of systemic and intratumoral controlled drug delivery properties.

Need of statins among un-diagnosed unaware Pakistanis via revised pool cohort equation by American heart association.

National diseases burden of Cardiovascular diseases is the top leading cause of death in Pakistan. In this study, Pakistani has been assessed for Atherosclerotic Cardiovascular Disease (ASCVD) on the basis of American Herat Association (AHA) guidelines. The aim of the study is to assess and inform about 10-year risk and life time risk in people residing in the largest metropolis city Karachi and aware about the use of statins as per revised Pooled Cohort Equation guidelines. The study sample size was 1760 with the age of 39 to >80 years with non-atherosclerotic diseases. Both genders without language barrier with or without elevated lipid were included. Clinical investigations including HDL, B.P and serum TG were included for calculating the ten year and life time risks on the basis of <5%, 5-7% and >7.5%. Results shows that the Odd ratio >1 found between age and TC however significant relationship (p<0.05) between gender, diabetes, hypertension and smokers were established. >50% study population required moderate and high intensity statin however <30% needed life style modification for reducing cardiac on risk. It is concluded that current recommendations are not for South Asians and may under or overlook the risks of individuals living in this continent. This study estimates the cardiovascular risk burden in the population of Karachi, Pakistan who were non-atherosclerotic undiagnosed and un-treated. This risk assessment may modify the algorithm and successfully identify the risk burden in present study groups.

Chewable cough tablets with improved palatability: A comparative phase II clinical trial.

Cough is the common disease condition which affects patients of every age. Numerous OTC medications available in community pharmacies however no antiviral treatment and even antibiotics has been shown to be effective without pre-existing lung infection. The treatment approach of medicinal herbs has been recognized for many decades and even longer for the treatment and prevention of cough. The aim of this study was to evaluate the safety and efficacy of Mukalbion poly herbal chewable tablets for the treatment of cough with improved palatability against a marketed brand (Poly herbal). For the formulation development of test group, the herbs were supplied by the Procurement department of Herbion Pakistan Pvt. Ltd. Althea officinalis (roots), Hedera helix (leaves) and Sisymbrium irio (seeds) were used for the manufacturing of Mukalbion (poly herbal, test group) chewable tablet. The comparative control clinical trial was carried out during a time frame of 07 months with sample size of 70 patients as per epidemiological software for sample size and each group contained 35 (±5) patients. Chewable tablets were administered and evaluated for effectiveness after 15 days of treatment. The data were collected by the patients through clinical trial questionnaire. The validated quality of life questionnaire (LCQ) was also used for assessment. The results were analyzed by applying paired sample T test by using IBM SPSS version 20.00. The p value was <0.005 at 95% confidence interval for cough variables including cough bouts, viscosity of sputum, chest congestion, sore throat and shortness of breath. The LCQ cough scale score was higher in test group as compared to control group. The test group also showed well tolerated in term of palatability. None of the patient claimed any of the side effects and no compliance were observed against the marketed brand.