Pharmacokinetics of vitamin dosage forms: A complete overview.

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier-based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency.

Outcomes associated with prolonged ECMO in COVID-19 associated ARDS: A single center experience.

PURPOSE OF STUDY: The COVID-19 pandemic has led to a significant increase in the use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a bridge to transplantation versus recovery. Unlike other etiologies of acute respiratory distress syndrome (ARDS), utilization of V-V ECMO in COVID-19 has been associated with longer duration of ECMO support requirements. Our team sought to evaluate outcomes associated with prolonged duration of ECMO support in this patient population. METHODS: Single-center retrospective review of patients who were placed on ECMO due to COVID-19 associated ARDS. Specifically examining outcomes-transplant free survival, mortality and discharge rates-of patients requiring V-V ECMO support for greater than 50 days. RESULTS: The median age of the cohort was 48 years and 13 patients (72%) were males. The median duration of ECMO support was 84 days (IQR 55-106). 11 patients (61%) had right ventricular dysfunction and 13 patients (72%) had pneumothoraces. There was a 33% percent (n = 6) mortality rate within cohort. One patient continues to require ECMO support at time of abstract submission. 11 patients (61%) patients were discharged, of which 3 patients required a lung transplant. SUMMARY: Prolonged V-V ECMO can be associated with comparable outcomes to conventional V-V ECMO runs that are relatively shorter in duration. With availability of device and staffing, prolonged ECMO runs can potentially be justified in a highly selected patient population.

Therapeutic drug monitoring in cystic fibrosis and associations with pulmonary exacerbations and lung function.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy have resulted in longer life expectancies, yet pulmonary exacerbations remain a leading cause of morbidity. Intravenous antibiotics is the mainstay treatment, however achieving adequate concentrations remains challenging. The effect of therapeutic drug monitoring (TDM) of beta-lactams on exacerbations and lung function has not been studied. METHODS: Patient demographics, antibiotic regimens, forced expiratory volume 1 s (FEV1), and exacerbation history was obtained from 32 patients with cystic fibrosis admitted for exacerbations. All patients were colonized with Pseudomonas aeruginosa, received CFTR therapy for at least one year, and had 3-month interval follow ups. Plasma concentrations, FEV1, and exacerbation history was obtained before and after therapeutic drug monitoring. This included peak and trough plasma concentrations of piperacillin-tazobactam and cefepime using liquid chromatography with mass spectrometry. T-test and Mann-Whitney U test were used to compare medians/means of FEV1 and pulmonary exacerbations pre and post-TDM as well as free trough-to-minimum inhibitory concentration ratio (fCmin/MIC) ≥1 and ≥ 4. RESULTS: TDM was associated with decreased exacerbations/year from 1.91 to 1.31 (p = 0.04) and among the cohort with >/ = 2 exacerbations per year, there was a longer exacerbation free interval after TDM (196.2 vs 103.7 days, p = 0.02). The decline in FEV1% predicted after therapeutic drug monitoring to the first exacerbation was -4.9 compared to -9.7 prior (p = 0.03). CONCLUSIONS: TDM for cystic fibrosis pulmonary exacerbations results in decreased pulmonary exacerbations, longer intervals to pulmonary exacerbation, and lower decline in FEV1% predicted.

Lung transplantation: candidate selection and timing of transplant.

PURPOSE OF REVIEW: Over the past two decades, lung transplant has become the mainstay of treatment for several end-stage lung diseases. As the field continues to evolve, the criteria for referral and listing have also changed. The last update to these guidelines was in 2014 and several studies since then have changed how patients are transplanted. Our article aims to briefly discuss these updates in lung transplantation. RECENT FINDINGS: This article discusses the importance of early referral of patients for lung transplantation and the concept of the 'transplant window'. We review the referral and listing criteria for some common pulmonary diseases and also cite the updated literature surrounding the absolute and relative contraindications keeping in mind that they are a constantly moving target. Frailty and psychosocial barriers are difficult to assess with the current assessment tools but continue to impact posttransplant outcomes. Finally, we discuss the limited data on transplantation in acute respiratory distress syndrome (ARDS) due to COVID19 as well as extracorporeal membrane oxygenation bridge to transplantation. SUMMARY: The findings discussed in this article will strongly impact, if not already, how we select candidates for lung transplantation. It also addresses some aspects of lung transplant such as frailty and ARDS, which need better assessment tools and clinical data.

Effects of deep sedation on sleep in critically ill medical patients on mechanical ventilation.

Atypical EEG patterns not consistent with standard sleep staging criteria have been observed in medical intensive care unit (ICU) patients. Our aim was to examine the relationship between sleep architecture and sedation in critically ill mechanically ventilated patients pre- and post-extubation. We performed a prospective observational repeated measures study where 50 mechanically ventilated patients with 31 paired analyses were examined at an academic medical centre. The sleep efficiency was 58.3 ± 25.4% for intubated patients and 45.6 ± 25.4% for extubated patients (p = .02). Intubated patients spent 76.33 ± 3.34% of time in non-rapid eye movement (NREM) sleep compared to 64.66 ± 4.06% of time for extubated patients (p = .02). REM sleep constituted 1.36 ± 0.67% of total sleep time in intubated patients and 2.06 ± 1.09% in extubated patients (p = .58). Relative sleep atypia was higher in intubated patients compared to extubated patients (3.38 ± 0.87 versus 2.79 ± 0.42; p < .001). Eleven patients were sedated with propofol only, 18 patients with fentanyl only, 11 patients with fentanyl and propofol, and 10 patients had no sedation. The mean sleep times on "propofol", "fentanyl", "propofol and fentanyl," and "no sedation" were 6.54 ± 0.64, 4.88 ± 0.75, 6.20 ± 0.75 and 4.02 ± 0.62 hr, respectively. The sigma/alpha values for patients on "propofol", "fentanyl", "propofol and fentanyl" and "no sedation" were 0.69 ± 0.04, 0.54 ± 0.01, 0.62 ± 0.02 and 0.57 ± 0.02, respectively. Sedated patients on mechanical ventilation had higher sleep efficiency and more atypia compared to the same patients following extubation. Propofol was associated with higher sleep duration and less disrupted sleep architecture compared to fentanyl, propofol and fentanyl, or no sedation.

Pulmonary artery sarcoma: Case report and review of the literature.

Pulmonary artery sarcoma is a rare malignancy with poor prognosis which can be misdiagnosed as pulmonary thromboembolism. We present a case of a middle age woman who initially diagnosed with presumptive pulmonary embolism that was later found to have pulmonary artery sarcoma. Symptoms, pathology, imaging characteristics and available treatments are discussed.

Short-term outcomes of pulmonary embolism: A National Perspective.

BACKGROUND: Pulmonary embolism (PE) is associated with significant morbidity and mortality in hospitalized patients. Real time data on 90-day mortality, bleeding, and readmission is sparse. METHODS: The study cohort was derived from the National Readmission Data (NRD) 2013 to 2014. PE was identified using International Classification of Diseases, ninth Revision (ICD-9-CM) code 415.11/3/9 in the primary diagnosis field. Any admission within 90 days of primary admission was considered a 90-day readmission. Readmission etiologies were identified by ICD-9 code in the primary diagnosis field. Co-primary outcomes were 90-day readmission and 90-day mortality. RESULTS: We identified 260 614 patients with primary admission PE, 55 659 (21.36%) patients were readmitted within 90 days. Most of them were of old age (age ≥ 65 years: 49.04%) and females (52.78%). Among the etiologies of readmission pulmonary disorders (22.94%) (Including recurrent PE 7.33%), malignancies (8.31%), and bleeding disorders (6.75%) were the most important causes of 90-day readmissions. On multivariate analysis, higher readmission rates and 90 days mortality were seen in patients with heart failure, chronic pulmonary disease, Anemia, malignancy, and with higher Charlson score. Patients with longer length of stay during primary admission and who discharged to short/long-term facility were more likely get readmitted and die in 90 days. Paradoxically, obese patients showed an inverse relationship with co-primary outcomes. CONCLUSIONS: Older female patients were more likely to have a pulmonary embolism. High-risk groups such as heart failure, chronic pulmonary disease, anemia, and malignancy need to be given extra attention to prevent worse outcomes.

Comparison of In-Hospital Outcomes and Readmission Rates in Acute Pulmonary Embolism Between Systemic and Catheter-Directed Thrombolysis (from the National Readmission Database).

There are sparse comparative data on in-hospital outcomes and readmission rates in patients with acute pulmonary embolism (PE) who receive systemic thrombolytics versus catheter-directed thrombolysis (CDT). The study cohort was derived from the National Readmission Database 2013 to 2014, subset of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. Systemic and CDT were identified using appropriate International Classification of Diseases, 9th Revision, Clinical Modification codes. The co-primary outcomes were in-hospital mortality and 30-day readmissions and secondary outcome was combined in-hospital mortality + gastrointestinal bleed + intracranial hemorrhage. We used propensity score match analysis without replacement using Greedy's algorithm to adjust for possible confounders. We identified a total of 4,426 patients (3,107: systemic thrombolysis and 1,319: CDT) with acute PE who were treated with thrombolysis. In our 2:1 propensity score algorithm, in-hospital mortality was lower in the CDT group (6.12%) versus systemic thrombolytics (14.94%) (odds ratio 0.37, 95% confidence interval 0.28 to 0.49, p <0.001). There was also a lower composite secondary outcome (in-hospital mortality + gastrointestinal bleed + intracranial hemorrhage) in patients who received CDT (8.42%) versus those who received systemic thrombolytics (18.13%) (odds ratio 0.41, 95% confidence interval 0.33 to 0.53, p <0.001). Thirty-day readmission was lower in patients with CDT group (7.65%) compared with systemic thrombolytics (10.58%, p = 0.009). In conclusion, in-hospital mortality, as well as bleeding during primary admission was significantly lower with CDT compared with systemic thrombolytics for patients with acute PE. There was also significant decrease in rate of readmissions among patients receiving CDT compared with systemic thrombolytics.

Challenges in the successful management of a case of acute intermittent porphyria in India.

Acute intermittent porphyria (AIP) is a rare metabolic disease involving a defect in haem biosynthesis resulting in the accumulation and excessive secretion of porphyrins and its precursors. Acute attacks present with episodes of severe abdominal pain, nausea, confusion and severe life-threatening seizures. A high index of suspicion is required for the initial diagnosis of AIP.

Cirrhosis: an unusual presentation of sickle cell disease.

Hepatobiliary complications of sickle cell disease are relatively rare but well recognised in literature. Clinical syndromes range from mild intrahepatic cholestasis and gallstones to life threatening sequestration crisis. Most patients, homozygous for sickle cell anaemia, present before adolescence. We report a case of an adult man with no prior symptoms who presented for the first time with decompensated cirrhosis, which was found to be due to underlying previously unrecognised sickle cell anaemia.

Non-Alcoholic Fatty Liver Disease (NAFLD) in Obesity.

BACKGROUND AND OBJECTIVES: Limited studies have been undertaken to characterize Non-Alcoholic Fatty Liver Disease (NAFLD) in the Indian population. The main objective of our study was to document the prevalence of NAFLD amongst a cohort of obese Indian patients and demonstrate its relationship with other components of the metabolic syndrome. METHODS: A total of 60 adult obese patients were subjected to a detailed history, clinical exam, anthropometric study and laboratory workup. Focus was on liver function and components of the metabolic syndrome like blood pressure, glycemic status and lipid profile. Subjects enrolled were divided into two groups Group A (n=48), with NAFLD and Group B (n=12) without NAFLD. The two groups were then compared amongst themselves as well as with data from previous similar studies. RESULTS: A comparison of the anthropometric measurements revealed a statistically significant difference between the Body mass index (BMI) and Waist Hip Ratio of the two groups and in the mean triglyceride values between the two groups. Although the mean bilirubin levels measured in the serum were not statistically different the mean levels of SGOT and SGPT in the two groups was found to be statistically significant. On the contrary no significant difference in the values of alkaline phosphatase and synthetic liver functions could be discerned. A statistically highly significant difference in the mean liver span is seen. INTERPRETATION AND CONCLUSIONS: NAFLD is common in Indian obese populations and is associated with significant differences in anthropometric, clinical, laboratory and ultrasonographic aspects as compared with obese individuals not affected with liver disease.

Impact of post-radiation biopsies on development of fistulae in patients with cervical cancer.

OBJECTIVE: In the post-radiation patient, late vascular sequelae and fibrosis predispose women to poor tissue healing, such that small tissue injuries could theoretically evolve into much larger ones such as fistulae. We sought to determine if a correlation exists between invasive procedures such as post-treatment biopsies and the subsequent development of gynecologic fistulae. METHODS: A retrospective review was performed evaluating all patients treated for cervical cancer at our institution between 1997 and 2010. Biopsies or pelvic surgeries were included if performed within the radiated field, and evaluated in a multivariate predictive model for development of gynecologic fistulae. RESULTS: Out of 325 total patients, 27 patients with fistulae were identified (8.2%). 14 fistulae (51.9%) were considered toxicity-related, 6 (22.2%) resulted from primary disease, and 7 (25.9%) were attributable to recurrent disease. Eighty-nine patients underwent an invasive procedure (55 biopsies and 34 pelvic surgeries). Recurrent and/or residual cancer was found in 28 (31.5%) specimens, and of the 61 patients who underwent an invasive procedure and were not found to have evidence of recurrent disease, 9 (14.8%) subsequently developed a fistula at a median 3.08 months. An elevated dose of radiation to the rectum (OR 1.001 for dose >72 Gy, p=0.0005), advancing tumor stage (OR 5.38 for stage III, OR 10.47 for stage IV, p=0.0288), and a post-radiation biopsy (OR 5.27, p=0.013) were significantly associated with fistula development. CONCLUSIONS: Performing a biopsy in an irradiated field is associated with a relatively low yield and significantly contributes to the risk for fistula development.

Widespread bullous fixed drug eruption.

A 53-year-old man developed a widespread erythematous eruption which rapidly evolved into fluid-filled bulla mostly involving the distal areas of all four limbs and erosions on the oral as well as anogenital mucosa. Based on clinical presentation, chronology of drug exposure, past events and histopathology as diagnosis of widespread bullous fixed drug eruption was made over Steven Johnson-toxic epidermal necrolysis syndrome. Steroids were deferred and the lesions healed with minimal pigmentation within a week. Differentiating between the two entities has been historically difficult, and yet can have significant therapeutic and prognostic implications.