Target Trial Emulation Using Hospital-Based Observational Data: Demonstration and Application in COVID-19.

Methodological biases are common in observational studies evaluating treatment effectiveness. The objective of this study is to emulate a target trial in a competing risks setting using hospital-based observational data. We extend established methodology accounting for immortal time bias and time-fixed confounding biases to a setting where no survival information beyond hospital discharge is available: a condition common to coronavirus disease 2019 (COVID-19) research data. This exemplary study includes a cohort of 618 hospitalized patients with COVID-19. We describe methodological opportunities and challenges that cannot be overcome applying traditional statistical methods. We demonstrate the practical implementation of this trial emulation approach via clone-censor-weight techniques. We undertake a competing risk analysis, reporting the cause-specific cumulative hazards and cumulative incidence probabilities. Our analysis demonstrates that a target trial emulation framework can be extended to account for competing risks in COVID-19 hospital studies. In our analysis, we avoid immortal time bias, time-fixed confounding bias, and competing risks bias simultaneously. Choosing the length of the grace period is justified from a clinical perspective and has an important advantage in ensuring reliable results. This extended trial emulation with the competing risk analysis enables an unbiased estimation of treatment effects, along with the ability to interpret the effectiveness of treatment on all clinically important outcomes.

Hypothyroidism is prevalent among adult women with chronic lower urinary tract symptoms.

OBJECTIVE: To define the prevalence of hypothyroidism in women with chronic lower urinary tract symptoms (LUTS) and to compare the severity of each symptom between patients with hypothyroidism and controls. SUBJECTS AND METHODS: In this prospective observational study, we screened all adult women who came to the urology clinic between March 2017 and September 2020, and enrolled patients with chronic LUTS in the study. We assessed thyroid function. We evaluated the severity of voiding and storage urinary symptoms by the International Prostate Symptom Score. We also assessed the severity of urge urinary incontinence (UUI) and stress urinary incontinence (SUI). For between-group analysis, we selected age-matched cases and controls and compared them regarding the distribution and severity of urinary symptoms. RESULTS: Seven hundred and twenty-five women with a mean age of 51.7 ± 14.0 years were included in the final analysis. Two hundred fifty-eight patients (35.6%) had hypothyroidism. Age-matched case and control groups consisting of 210 patients each were selected. There was no significant difference in the severity and distribution of voiding LUTS and UUI between the study groups (P values >0.05). The severity of storage symptoms was lower in patients with hypothyroidism (P = 0.04). Sixty-seven patients with hypothyroidism (31.9%) had SUI, which was significantly higher than controls (23.3%) (P = 0.03). CONCLUSION: More than one-third of women with chronic LUTS have hypothyroidism which is much more frequent than in the general population. We also suggest a possible relationship between hypothyroidism and the severity of SUI and an inverse relationship between hypothyroidism and storage symptoms.

Risk Factors for the Mortality in Hospitalized Patients with COVID-19: A Brief Report.

The cumulative rate of death of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated better recognizing the risk factors of the disease and the COVID-19-induced mortality. This cross-sectional study aimed to determine the potential risk factors that predict COVID-19-related mortality concentrating on the initial recorded laboratory tests. We extracted admission's medical records of a total of 136 deaths related to COVID-19 and 272 discharged adult inpatients (≥18 years old) related to four referral centers from February 24th to April 12th, 2020, in Isfahan, Iran, to figure out the relationship between the laboratory findings and mortality beyond demographic and clinical findings. We applied the independent sample t test and a chichi square test with SPSS software to compare the differences between the survivor and non-survivor patients. A P value of less than 0.05 was considered significant. Our results showed that greater length of hospitalization (P≤0.001), pre-existing chronic obstructive pulmonary disease (P≤0.001), high pulse rate, hypoxia (P≤0.001), and high computed tomography scan score (P<0.001), in addition to high values of some laboratory parameters, increase the risk of mortality. Moreover, high neutrophil/lymphocyte ratio (OR, 1.890; 95% CI, 1.074-3.325, P=0.027), increased creatinine levels (OR, 15.488; 95% CI, 0.801-299.479, P=0.07), and elevated potassium levels (OR, 13.400; 95% CI, 1.084-165.618, P=0.043) independently predicted in-hospital death related to COVID-19 infection. These results emphasized the potential role of impaired laboratory parameters for the prognosis of fatal outcomes in adult inpatients.

Hemoperfusion in patients with severe COVID-19 respiratory failure, lifesaving or not?

BACKGROUND: The new coronavirus outbreak quickly filled hospital beds and stunned the world. Intensive care is required for 5% of patients, and the mortality rate for critically ill patients is 49%. The "cytokine storm" is considered as the main cause of pathogenesis for coronavirus disease-19 (COVID-19)-related respiratory failure, hemoperfusion may be a modality for treatment of disease. MATERIALS AND METHODS: Thirty-seven an patients with positive real-time polymerase chain reaction for SARStions2 in an upper respiratory tract sample or typical chest computed tomography lesion were eligible for this case-control study. Patients meeting the criteria for hemoperfusion including clinical and laboratory indices, were evaluated for outcomes such as hospitalization length and mortality. Patients were divided into three groups, i.e., patients who received hemoperfusion without a need for mechanical ventilation (MV), patients who received hemoperfusion before MV, and patients who received hemoperfusion after MV. RESULTS: Among 37 patients with COVID-19 respiratory failure, 32% were female with a mean age of 55.54 (standard deviation 14.1) years. There was no statistically significant difference between the three groups in terms of length of hospital stay and intensive care unit (ICU) stay (P-tayns: 0.593 and 0.243, respectively, confidence interval [CI]: 95%). Heart rate, respiratory rate, PaO2/FIO2, high-sensitivity C-reactive protein, and ferritin significantly improved after the application of hemoperfusion in all groups (P < 0.05, CI: 95%). CONCLUSION: It seems that applying hemoperfusion in the inflammatory phase of the disease, especially before the intubation, reduce the need for MV. However, hemoperfusion does not have any impacts on the duration of hospital and ICU stay.

Testosterone and Zinc Supplementations on Renal Ischemia-Reperfusion Injury in Orchiectomized Rats.

BACKGROUND: Renal ischemia-reperfusion (IR) injury has numerous deleterious effects on the kidney function. An experimental investigation was conducted to determine the possible protective role of testosterone (TES) and zinc (Zn) supplementations on the kidney function after IR injury in orchiectomized rats. METHODS: Orchiectomized rats (n = 32) were divided into the five groups as sham operated (Group 1), IR (Group 2), IR pretreatment with TES (IR + TES, Group 3), Zn (IR + Zn, Group 4), and TES + Zn (IR + TES + Zn, Group 5). Twenty-four hours' post-IR injury, the animals were sacrificed and the required parameters were measured. RESULTS: The results revealed that there were not any significant difference in serum levels of creatinine (Cr), nitrite and malondialdehyde (MDA), Cr clearance (ClCr), renal sodium (Na) load, and percentage of Na excretion (ENa%) between sham and IR groups. The pretreatment with TES and Zn either alone or combine did not alter the serum levels of Cr, nitrite and MDA, and ClCr, Na load, and ENa%. However, pretreatment with Zn, TES, or combined altered kidney weight, kidney tissue levels of nitrite and MDA, and urine flow in IR groups. CONCLUSIONS: The orchiectomy itself performed protective effect against renal IR injury. However, pretreatment with Zn or TES may not alter kidney function against renal IR in orchiectomized rats.