Effect of cardiopulmonary bypass on cytochrome P450 enzyme activity: implications for pharmacotherapy

For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug–drug interactions. Clinically significant changes in drug PK during CPB are likely to be prominent for drugs where CYP metabolism is a major clearance (CL) mechanism. However, clinical data from patients undergoing CPB surgery in support of this hypothesis are lacking, leaving a significant knowledge gap. In this review, we address the effects of CPB on the release of pro-inflammatory cytokines, in surgeries with and without CPB, both pre and post initiation of surgery. We reviewed literature to explore the relationship between the release of pro-inflammatory cytokines, and the expression and activities of CYP enzymes. Through this approach, we provide new insight on the effects of CPB on the PK of drugs administered to patients in the clinical setting. Future research to address this knowledge gap will have considerable impact to assist clinicians with optimizing pharmacotherapy in this patient population.     

Pulmonary Function Testing in Patients with Tracheostomies: Feasibility and Technical Considerations

Purpose

Pulmonary function testing (PFT) in patients with tracheostomies has been perceived as difficult to perform and clinically unreliable. We studied the feasibility, quality, repeatability and clinical significance of PFT.

Methods

Patients with tracheostomies that underwent PFT from January 1, 2010 to February 29, 2012 were identified. Clinical history and PFT data were reviewed retrospectively.

Results

Fifty patients (88% men) were identified. Forty-seven (94%) patients were able to perform PFT. Acceptable repeatability was obtained for FVC in 39 (83%) and for FEV1 in 41 (87%). Patients with tracheostomies showed difficulty in meeting ATS end-of-test criteria; only 9 (19%) met plateau criteria and 25 (53%) had exhalation times of greater than 6 s. Obstructive pattern was observed in 30 (64%) and restrictive pattern in 9 (19%). DLCO measurements were attempted in 43 patients and satisfactorily obtained in 34 (79%).

Conclusions

PFT can be performed with reliability in patients with tracheostomies, and they are useful for detecting and classifying types of lung dysfunction.

     

Typhoid fever caused by a typical variants of Salmonella typhi--a preliminary report

In the study carried out from, February, 1996 to January, 1999. 42 (33.9%) a typical variants of S typhi which fermented sucrose were encountered. This variant was identified as of antigenic structure 9, 12, v1, d1 and typed as phage type E1 and Bio type I.     

Assessing Coronavirus Fear in Indian Population Using the Fear of COVID-19 Scale

International Journal of Mental Health and Addiction - The current study aimed to determine the level of fear of COVID-19 among Indian residents using the Fear of COVID-19 Scale (FCV-19S) and...     

What works? Interventions for maternal and child undernutrition and survival

We reviewed interventions that affect maternal and child undernutrition and nutrition-related outcomes. These interventions included promotion of breastfeeding; strategies to promote complementary feeding, with or without provision of food supplements; micronutrient interventions; general supportive strategies to improve family and community nutrition; and reduction of disease burden (promotion of handwashing and strategies to reduce the burden of malaria in pregnancy). We showed that although strategies for breastfeeding promotion have a large effect on survival, their effect on stunting is small. In populations with sufficient food, education about complementary feeding increased height-for-age Z score by 0.25 (95% CI 0.01-0.49), whereas provision of food supplements (with or without education) in populations with insufficient food increased the height-for-age Z score by 0.41 (0.05-0.76). Management of severe acute malnutrition according to WHO guidelines reduced the case-fatality rate by 55% (risk ratio 0.45, 0.32-0.62), and recent studies suggest that newer commodities, such as ready-to-use therapeutic foods, can be used to manage severe acute malnutrition in community settings. Effective micronutrient interventions for pregnant women included supplementation with iron folate (which increased haemoglobin at term by 12 g/L, 2.93-21.07) and micronutrients (which reduced the risk of low birthweight at term by 16% (relative risk 0.84, 0.74-0.95). Recommended micronutrient interventions for children included strategies for supplementation of vitamin A (in the neonatal period and late infancy), preventive zinc supplements, iron supplements for children in areas where malaria is not endemic, and universal promotion of iodised salt. We used a cohort model to assess the potential effect of these interventions on mothers and children in the 36 countries that have 90% of children with stunted linear growth. The model showed that existing interventions that were designed to improve nutrition and prevent related disease could reduce stunting at 36 months by 36%; mortality between birth and 36 months by about 25%; and disability-adjusted life-years associated with stunting, severe wasting, intrauterine growth restriction, and micronutrient deficiencies by about 25%. To eliminate stunting in the longer term, these interventions should be supplemented by improvements in the underlying determinants of undernutrition, such as poverty, poor education, disease burden, and lack of women's empowerment.     

Association of Karnofsky Performance Status with waitlist mortality among older and younger adults awaiting kidney transplantation

Patients with end-stage renal disease (ESRD) have impaired functional status compared with the general population. We sought to explore the association between Karnofsky Performance Status (KPS) and death/delisting from the kidney transplantation waitlist and whether this association differed by age. Patients listed for single-organ kidney transplantation in the United Network for Organ Sharing/Organ Procurement and Transplantation Network from January 1, 2015, to January 1, 2018, were included. We performed competing-risk regression analyses to determine the association between KPS (“Severely impaired”, “Moderately impaired”, “Non-impaired”) and death/delisting, with deceased-donor kidney transplantation as a competing risk. We tested for interactions between age and KPS on death/delisting. Of the 89,819 patients analyzed, 39% were impaired (KPS < 80) and 20% were aged ≥ 65 years. Older age and lower KPS were independently associated with higher risk of death/delisting (age 45-64 years, HR 1.97 [95% CI 1.73-2.24]; age ≥ 65 years, HR 3.62 [95% CI 3.33-3.92] compared with age < 45 years; moderately impaired, HR 1.68 [95% CI 1.45-1.95]; severely impaired, HR 4.80 [95% CI 3.71-6.21] compared with non-impaired). Lower KPS was associated with higher risk of death/delisting among all ages, but this effect was slightly less pronounced among individuals aged ≥ 65 years. Performance status should be used when counseling patients with ESRD on their risks for death/delisting.