79 research outputs found

    Does Voracious Behavior favor Efficient Market Hypothesis? Role of Performance Measures

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    Greed plays an important in the fluctuations of stock prices because investors want profits irrespective of the risk taken by them. This study aims to determine, whether, in times of rising trends in the market, greediness is good for the investor or not. Secondly, investors can get high profits by beating the market or not. The already formed deciles portfolios of listed companies on NYSE, AMEX, and NASDAQ based on size and book to market value are taken from the Kenneth R. French data library from Dec 1994 to Dec 2021. Sharpe, Treynor, and Sortino ratios are used as the measure of the performance of portfolios. Ordinal logistic regression is used to calculate the probability at different benchmark levels to determine, whether the investor gets the profit by beating the market or not. The results show that the investor who used the Sharpe ratio has an average 85% probability of getting a profit of more than 75% of the benchmark of S&P-500 in all periods. Thus, the investors’ greediness is good in the long run if the investor considers total risk and can beat the market. By using the Sortino and Treynor ratio, there is an average 50% probability of achieving the profit up to the benchmark which is S&P-500. This means that the investors are not able to beat the market thus, support the efficient market hypothesis by considering the downside and market risk

    Clinico-pathological profile and outcomes of patients with polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis: a tertiary care center experience from southern Pakistan

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    Background: The “Philadelphia Negative Classic Myeloproliferative Neoplasms” include polycythaemia vera (PV), essential thrombocythaemia (ET) andidiopathic myelofibrosis (IMF). These three disorders share several clinical and laboratory features including JAK2 V617F mutation. Our objectives were to determine the clinicoat hological profile and outcomes of Pakistani patients with polycythaemia vera (PV), essential thrombocythaemia (ET) and idiopathic myelofibrosis (IMF) in order to have an insight regarding behaviour of these conditions. Methods: A retrospective analysis of all the cases of PV, ET and IMF diagnosed at our institute from January 1995 to December 2013 was performed.Age, gender, clinical presentation, laboratory investigations, treatment provided and duration of follow up were included for analysis. Appropriatestatistics were utilized for calculation of data. Results: A total of 58 patients were diagnosed as PV, ET or IMF during the study period. Male to female ratio was 1.1:1Forty five percent (n=2) patients came to medical attention due to abnormal laboratory results, 3 had cerebrovascular events, 3 had pruritus, and 1 patient each with gangrene and BuddChiari syndrome. Haemorrhag was not seen in any patient. Sixty percent (n=35) patients were treated with phlebotomy, hydroxyurea and aspirin alone or in combination. None of the patients transformed to myelofibrosis (MF) ormyelodysplasia (MDS) during the mean (±SD) followupperiod of 57.2±50 months.One patient with ET transformed to acute myeloid leukaemia9 yearsafter the diagnosis. Conclusions: This study demonstrated a relatively more benign form of PV, ET and IMF with lesser frequency of symptoms, good response to treatment andless likelihood of transformation to MF, MDS or AM

    COVID-19 and liver injury: A systematic review and meta-analysis

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    Background and Aims: The prevalence and extent of liver damage in coronavirus disease 2019 (COVID-19) patients remain poorly understood, primarily due to small-sized epidemiological studies with varying definitions of “liver injury”. We conducted a meta-analysis to derive generalizable, well-powered estimates of liver injury prevalence in COVID-19 patients. We also aimed to assess whether liver injury prevalence is significantly greater than the baseline prevalence of chronic liver disease (CLD). Our secondary aim was to study whether the degree of liver injury was associated with the severity of COVID-19.Materials and Methods: Electronic databases (PubMed and Scopus) were systematically searched in June 2020 for studies reporting the prevalence of baseline CLD and current liver injury in hospitalized COVID-19 patients. Liver injury was defined as an elevation in transaminases \u3e3 times above the upper limit of normal. For the secondary analysis, all studies reporting mean liver enzyme levels in severe versus non-severe COVID-19 patients were included. A random-effects model was used for meta-analysis. Proportions were subjected to arcsine transformation and pooled to derive pooled proportions and corresponding 95% confidence intervals (CIs). Subgroup differences were tested for using the chi-square test and associated p-value. Means and their standard errors were pooled to derive weighted mean differences (WMDs) and corresponding 95% CIs.Results: Electronic search yielded a total of 521 articles. After removal of duplicates and reviewing the full-texts of potential studies, a total of 27 studies met the inclusion criteria. Among a cohort of 8,817 patients, the prevalence of current liver injury was 15.7% (9.5%-23.0%), and this was significantly higher than the proportion of patients with a history of CLD (4.9% [2.2%-8.6%]; p \u3c 0.001). A total of 2,900 patients in our population had severe COVID-19, and 7,184 patients had non-severe COVID-19. Serum ALT (WMD: 7.19 [4.90, 9.48]; p \u3c 0.001; I2 = 69%), AST (WMD: 9.02 [6.89, 11.15]; p \u3c 0.001; I2 = 73%) and bilirubin levels (WMD: 1.78 [0.86, 2.70]; p \u3c 0.001; I2 = 82%) were significantly higher in patients with severe COVID-19 when compared to patients with non-severe disease. Albumin levels were significantly lower in patients with severe COVID-19 (WMD: -4.16 [-5.97, -2.35]; p \u3c 0.001; I2 = 95%).Conclusions: Patients with COVID-19 have a higher than expected prevalence of liver injury, and the extent of the injury is associated with the severity of the disease. Further studies are required to assess whether hepatic damage is caused by the virus, medications, or both

    Performance of the TIMI risk score in predicting mortality after primary percutaneous coronary intervention in elderly women: Results from a developing country

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    Background: Despite women undergoing primary percutaneous coronary intervention (PPCI) having a higher rate of adverse outcomes than men, data evaluating prognostic risk scores, especially in elderly women, remains scarce. This study was conducted to validate the predictive value of Thrombolysis in Myocardial Infarction (TIMI) risk score in elderly female patients. Materials and Methods: This was a retrospective analysis of elderly (\u3e65 years) female patients who underwent PPCI for ST-elevated myocardial infarction (STEMI) from October 2016 to September 2018. Patients\u27 demographic details and elements of TIMI risk score including age, co-morbidities, Killip classification; weight, anterior MI and total ischemic time were extracted from hospital records. The primary outcome was in-hospital mortality and post-discharge mortality reported on telephonic follow-up. Results: A total of 404 elderly women with a median age of 70 years were included. The mean TIMI score was 5.25±1.45 with 40.3% (163) patients of TIMI score \u3e 5. In-hospital mortality rate was 6.4% (26) and was found to be associated with TIMI score (p\u3c0.001). The in-hospital mortality rate increased from 3.1% at TIMI score of 0-4 to 34.6% at the score of 8. On follow-up (16.43±7.40 months) of 211 (55.8%) patients, the overall mortality rate was 20.3%, and this was also associated with TIMI score (p\u3c0.001). The mortality rate increased from 5.6% at the score of 0-4 to 54.5% at the score of 8. The predictive values (area under the curve) of TIMI risk score for in-hospital and post-discharge mortality were 0.709 (95% CI 0.591-0.827; p \u3c0.001) and 0.689 (95% CI 0.608-0.770; p \u3c0.001), respectively. Conclusion: Increased adverse outcomes were observed with higher TIMI risk score for in hospital and post-discharge follow-up. Therefore, the prognostic TIMI risk score is a robust tool in predicting both in-hospital as well as post-discharge mortality in elderly females

    Utility of the CHA2DS2-VASc score for predicting ischaemic stroke in patients with or without atrial fibrillation: a systematic review and meta-analysis

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    AIMS: Anticoagulants are the mainstay treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), and the CHA2DS2-VASc score is widely used to guide anticoagulation therapy in this cohort. However, utility of CHA2DS2-VASc in NVAF patients is debated, primarily because it is a vascular scoring system, which does not incorporate atrial fibrillation related parameters. Therefore, we conducted a meta-analysis to estimate the discrimination ability of CHA2DS2-VASc in predicting ischaemic stroke overall, and in subgroups of patients with or without NVAF. METHODS AND RESULTS: PubMed and Embase databases were searched till June 2020 for published articles that assessed the discrimination ability of CHA2DS2-VASc, as measured by C-statistics, during mid-term (2-5 years) and long-term (\u3e5 years) follow-up. Summary estimates were reported as random effects C-statistics with 95% confidence intervals (CIs). Seventeen articles were included in the analysis. Nine studies (n = 453 747 patients) reported the discrimination ability of CHA2DS2-VASc in NVAF patients, and 10 studies (n = 138 262 patients) in patients without NVAF. During mid-term follow-up, CHA2DS2-VASc predicted stroke with modest discrimination in the overall cohort [0.67 (0.65-0.69)], with similar discrimination ability in patients with NVAF [0.65 (0.63-0.68)] and in those without NVAF [0.69 (0.68-0.71)] (P-interaction = 0.08). Similarly, at long-term follow-up, CHA2DS2-VASc had modest discrimination [0.66 (0.63-0.69)], which was consistent among patients with NVAF [0.63 (0.54-0.71)] and those without NVAF [0.67 (0.64-0.70)] (P-interaction = 0.39). CONCLUSION: This meta-analysis suggests that the discrimination power of the CHA2DS2-VASc score in predicting ischaemic stroke is modest, and is similar in the presence or absence of NVAF. More accurate stroke prediction models are thus needed for the NVAF population

    Distribution of chromosomal abnormalities commonly observed in adult acute myeloid leukemia in Pakistan as predictors of prognosis

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    Objective: The heterogenous response to treatment in acute myeloid leukemia (AML) can be attributed largely to the difference in cytogenetic features identified in between cases. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of these patients. The study was conducted to determine the distribution of cytogenetic abnormalities in Pakistani adult patients with AML in order to have insights regarding behavior of the. method: A retrospective analysis of all the cases of AML (≥15years old) diagnosed at Aga Khan University from January 2011 to December 2016 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Result: A total of 321 patients were diagnosed with AML during the study period, of which 288 samples successfully yielded metaphase chromosomes. The male to female ratio was 1.7:1. A normal karyotype was present in 61% (n=176) of the cases whereas, 39% (n=112) had an abnormal karyotype. Of the abnormal cases, t (8;21) (q22;q22) and t (15;17) (q22;q12) were identified in 8.3% and 4.9% cases respectively. Adverse prognostic cytogenetic subgroups including complex karyotype, monosomy 7 and t(6;9)(p23;q34) were identified in 9%, 1% and 0.7% patients respectively. Conclusion: This largest cytogenetic data in adult AML from Pakistan showed comparable prevalence of favorable prognostic karyotype to international data. The prevalence of specific adverse prognostic karyotype was low

    Robustness of outcomes in trials evaluating sodium–glucose co‐transporter 2 inhibitors for heart failure

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    Aims: Recent trials have evaluated sodium–glucose co‐transporter 2 inhibitors in patients with heart failure (HF). We sought to assess the robustness of findings from these trials using the fragility index (FI). Methods and results: Fragility index is defined as the minimum number of patients that must be moved from the ‘non‐event’ to the ‘event’ group to turn a statistically significant result to non‐significant. In addition to FI, fragility quotient [(FQ); FI divided by the sample size] was calculated to assess the proportion of events that must be moved to change the significance. For statistically non‐significant outcomes, reverse fragility index (RFI) and reverse fragility quotient (RFQ) were calculated. Robustness of findings after pooling data from all three trials was also assessed. A robust reduction in first HF hospitalization or cardiovascular mortality was seen with dapagliflozin (FI = 62 and FQ = 0.013), empagliflozin (FI = 50 and FQ = 0.013), and sotagliflozin (FI = 60 and FQ = 0.049). Dapagliflozin nominally improved all‐cause and cardiovascular mortality, with modest FI (n = 8 and 5) and FQ (0.002 and 0.001). Empagliflozin and sotagliflozin did not demonstrate statistically significant reductions in all‐cause mortality, with modest RFI (empagliflozin: RFI = 26 and RFQ = 0.007; sotagliflozin: RFI = 6 and RFQ = 0.005). A similar trend was seen with cardiovascular mortality (empagliflozin: RFI = 24 and RFQ = 0.006; sotagliflozin: RFI = 7 and RFQ = 0.006). Upon meta‐analysis, the result for first HF hospitalization or cardiovascular mortality was robust (FI = 95 and FQ = 0.010). The reductions in all‐cause (FI = 12 and FQ = 0.001) and cardiovascular mortality (FI = 9 and FQ = 0.001), while statistically significant, were fragile. Conclusion: Improvement in the composite outcome of first HF hospitalization or cardiovascular death was highly concordant and robust across sodium–glucose co‐transporter 2 inhibitor trials. In contrast, secondary endpoints of all‐cause and cardiovascular mortality were statistically fragile, underscoring the need to power trials for mortality to fully understand the benefit of therapies on fatal events

    Blinded Withdrawal of Long-Term Randomized Treatment With Empagliflozin or Placebo in Patients With Heart Failure.

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    BACKGROUND: It is not known whether the benefits of sodium-glucose cotransporter 2 inhibitors in heart failure persist after years of therapy. METHODS: In the EMPEROR-Reduced (Empagliflozin Outcome Trials in Chronic Heart Failure With Reduced Ejection Fraction) and EMPEROR-Preserved (Empagliflozin Outcome Trials in Chronic Heart Failure With Preserved Ejection Fraction) trials, patients with heart failure were randomly assigned (double-blind) to placebo or empagliflozin 10 mg/day for a median of 16 and 26 months, respectively. At the end of the trials, 6799 patients (placebo 3381, empagliflozin 3418) were prospectively withdrawn from treatment in a blinded manner, and, of these, 3981 patients (placebo 2020, empagliflozin 1961) underwent prespecified in-person assessments after ≈30 days off treatment. RESULTS: From 90 days from the start of closeout to the end of double-blind treatment, the annualized risk of cardiovascular death or hospitalization for heart failure was lower in empagliflozin-treated patients than in placebo-treated patients (10.7 [95% CI, 9.0-12.6] versus 13.5 [95% CI, 11.5-15.6] events per 100 patient-years, respectively; hazard ratio 0.76 [95% CI, 0.60-0.96]). When the study drugs were withdrawn for ≈30 days, the annualized risk of cardiovascular death or hospitalization for heart failure increased in patients withdrawn from empagliflozin but not in those withdrawn from placebo (17.0 [95% CI, 12.6-22.1] versus 14.1 [95% CI, 10.1-18.8] events per 100 patient-years for empagliflozin and placebo, respectively). The hazard ratio for the change in risk in the patients withdrawn from empagliflozin was 1.75 (95% CI, 1.20-2.54), P=0.0034, whereas the change in the risk in patients withdrawn from placebo was not significant (hazard ratio 1.12 [95% CI, 0.76-1.66]); time period-by-treatment interaction, P=0.068. After withdrawal, the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score declined by 1.6±0.4 in patients withdrawn from empagliflozin versus placebo (P<0.0001). Furthermore, withdrawal of empagliflozin was accompanied by increases in fasting glucose, body weight, systolic blood pressure, estimated glomerular filtration rate, N-terminal pro-hormone B-type natriuretic peptide, uric acid, and serum bicarbonate and decreases in hemoglobin and hematocrit (all P<0.01). These physiological and laboratory changes were the inverse of the effects of the drug seen at the start of the trials during the initiation of treatment (≈1-3 years earlier) in the same cohort of patients. CONCLUSIONS: These observations demonstrate a persistent effect of empagliflozin in patients with heart failure even after years of treatment, which dissipated rapidly after withdrawal of the drug. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT03057977 and NCT03057951

    Soluble guanylate cyclase stimulators in patients with heart failure with reduced ejection fraction across the risk spectrum

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    Patients with heart failure with reduced ejection fraction (HFrEF) have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Soluble guanylate cyclase (sGC) stimulators have the potential to lower this risk by modifying the nitric oxide–sGC–cyclic guanosine monophosphate cascade – a pathophysiological pathway that has been targeted with limited success in HFrEF previously. Vericiguat, an sGC stimulator, was shown to improve outcomes in patients with HFrEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. However, this trial included patients with recently worsening disease. In this brief review, we discuss the rationale of evaluating sGC stimulators in lower-risk HFrEF patients. First, all key HFrEF medications have been evaluated in both higher- and lower-risk populations, and the treatment effect is not always consistent across the risk spectrum. Second, pre-clinical studies and post-hoc studies of the VICTORIA trial have suggested that sGC stimulators may have cardioprotective effects – these effects may be more apparent when the medication is initiated earlier in the disease process. Third, the effect of vericiguat on cardiovascular mortality remains uncertain and a trial with a longer follow-up in a lower-risk population may allow better assessment of its effect on cardiovascular mortality. Therefore, there is a pertinent need to investigate the effects of vericiguat in optimally treated, low-risk HFrEF patients (i.e. those without recently worsening heart failure).</p

    Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

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    Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations
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