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BackgroundLung transplantation can provide quality of life and survival benefits for patients with coronavirus disease 2019 (COVID-19)–associated end-stage lung disease. Characteristics and outcomes of these lung transplant recipients are limited to mostly single-center experiences or provide a short-term follow-up.MethodsCharacteristics of deceased donors and adult lung transplant recipients for COVID-19–associated end-stage lung disease between August-2020 and June-2022 were analyzed using deidentified United Network for Organ Sharing database. Post-transplant patient survival of COVID-19 recipients was analyzed and compared with non–COVID-19 recipients. Secondary outcomes were length of hospitalization, post-transplant complications, and rates of organ rejection.ResultsDuring the study period, 400 lung transplants for COVID-associated end-stage lung disease comprised 8.7% of all lung transplants performed in United States. In the COVID-19 group, Hispanic males received lung transplants at significantly higher rates. The COVID-19 group was younger and had greater need for intensive care unit stay, mechanical ventilation, hemodialysis, extracorporeal membrane oxygenation support, and receipt of antibiotics pre-lung transplant. They had higher lung allocation score, with a shorter wait-list time and received more double lung transplants compared with non–COVID-19 recipients. Post-transplant, the COVID-19 cohort had longer hospital stays, with similar 1-year patient survival (COVID, 86.6% vs non–COVID, 86.3%). Post-transplant, COVID-19–associated deaths were 9.2% of all deaths among lung transplant recipients.ConclusionsLung transplantation offers a effective option for carefully selected patients with end-stage lung disease from prior COVID-19, with short-term and long-term outcomes similar to those for lung transplant recipients of non–COVID-19 etiology.

Extracorporeal Membrane Oxygenation (ECMO) has revolutionized the treatment of refractory cardiac and respiratory failure, and its use continues to increase, particularly in adults. However, ECMO-related morbidity and mortality remain high.In this review, we investigate and expand upon the current state of the art in thoracic transplant and extracorporeal life support (ELS). In particular, we examine recent increase in incidence of heart transplant in patients supported by ECMO; the potential changes in patient care and selection for transplant in the years prior to updated United Network for Organ Sharing (UNOS) organ allocation guidelines versus those in the years following, particularly where these guidelines pertain to ECMO; and the newly revived practice of heart-lung block transplants (HLT) and the prevalence and utility of ECMO support in patients listed for HLT.Our findings highlight encouraging outcomes in patients bridged to transplant with ECMO, considerable changes in treatment surrounding the updated UNOS guidelines, and complex, diverse outcomes among different centers in their care for increasingly ill patients listed for thoracic transplant. This article is protected by copyright. All rights reserved.

We conducted public health investigations of 8 organ transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 infection. Findings suggest the most likely source of transmission was community or healthcare exposure, not the organ donor. Transplant centers should educate transplant candidates and recipients about infection prevention recommendations.

Highlights • Ocimum sanctum hydroalcoholic extract (OSHE) potential as an adjuvant to antiepileptic drugs (AEDs) carbamazepine and phenytoin is studied in maximal electroshock seizure (MES) model in male Wistar rats. • OSHE per se showed 50% seizure protection and its combination enhanced potential of AEDs’ sub-maximal dose. • Neuroprotection was evident after combination of OSHE with AEDs as per Morris water maze and elevated plus maze test. • OSHE treatment has minimal pharmacokinetic interaction with carbamazepine and phenytoin., Purpose This study assessed adjuvant potential of Ocimum sanctum hydroalcoholic extract (OSHE) with antiepileptic drugs (AEDs) carbamazepine (CBZ) and phenytoin (PHT) in maximal electroshock seizure (MES) model in male Wistar rats. Material and Methods Pharmacodynamic effect of OSHE (1000 mg/kg) was assessed through seizure protection potential, neurobehavioral tests and oxidative stress estimation in MES model after 14 days administration of OSHE alone or combination with maximal (M) and sub-maximal (SM) dose of CBZ or PHT. Pharmacokinetic interaction of OSHE with AEDs was also assessed after 14 days of drug treatment. Results OSHE per se showed 50% protection against MES-induced seizures. Combination of OSHE with AEDs’ SM dose enhanced its seizure protection potential. Significant reduction in duration of tonic hind limb extension was observed in CBZ-SM + OSHE as compared to control group (p = 0.006). Among neurobehavioral tests in Morris water maze test rats of CBZ-M + OSHE took significantly less time to reach the platform (p = 0.022) and spent more time in target quadrant (p = 0.016) as compared to other groups. Similarly, rats of PHT-SM + OSHE group spent significantly more time in the target quadrant (p = 0.013). In elevated plus maze test, CBZ-M + OSHE had significantly decreased transfer latency compared to other groups (p = 0.013). OSHE alone treated group had significantly lower oxidative stress as compared to other groups. No significant pharmacokinetic interaction was observed between OSHE and AEDs (CBZ, PHT). Conclusion Ocimum’s potential of enhanced seizure protection and neuroprotection along with minimal drug interaction with AEDs substantiate its adjuvant role in the management of epilepsy.

Centella asiatica (CA) is commonly used herbal medicine for treatment of epilepsy. CA has CYP2C9, CYP2D6 and CYP3A4 enzymes inhibition property and used as an adjuvant therapy with conventional antiepileptic drugs (AEDs). That may be responsible for herb-drug interaction.The present study was planned to evaluate interactions profile of hydroalcoholic extract Centella asiatica (HECA) with antiepileptic drugs in experimental models of epilepsy in rats.Wistar rats (175-200 g) were used. In the pharmacodynamic interaction study, seizures were induced using pentylenetetrazole (PTZ) (60 mg/kg, i.p.) and maximal electroshock seizure (MES) (70 mA for 0.2 s). The therapeutic and sub-therapeutic doses of valproate (VPA) and phenytoin (PHT) were co-administrated with HECA in PTZ and MES model of seizures respectively. Behavioural parameters were assessed using elevated plus maze test and passive avoidance paradigm. Rat brain oxidative stress parameters were also assessed. In the pharmacokinetic interaction study, the serum levels of the VPA and PHT were estimated at different time intervals by HPLC and pharmacokinetic parameters were analyzed by WinNonlin software.The VPA and PHT produced complete protection against seizures in their therapeutic doses but not with sub-therapeutic doses. However, co-administration of HECA with a sub-therapeutic dose of VPA and PHT enhanced the protection of seizures and significantly (p 0.001) attenuated the seizure induced oxidative stress and cognitive impairment. It also significantly increased (p 0.001) serum levels of VPA and PHT. The alterations in pharmacokinetic parameters (maximum serum concentration, area under the curve, clearance) of AEDs were also found with co-administration of HECA.The results suggested that co-administration of HECA could improve the therapeutic efficacy of VPA and PHT. But, alteration in pharmacokinetic parameters revel that needs critical medical supervision to avoid any toxic reactions.

For effective control of seizures, antiepileptic drugs (AEDs) are administered at higher dose which is associated with several adverse effects. This study envisaged antiepileptic and neuroprotective potential of Tulsi, a commonly used herb for its immunomodulatory property. The optimal dose of Ocimum sanctum hydroalcoholic extract (OSHE) was determined using maximal electroshock seizure (MES)- and pentylenetetrazol (PTZ)-induced seizure models in Wistar rats (200-250g) after administering OSHE (200-1000mg/kg) orally for 14days. For interaction study, OSHE optimal dose in combination with maximum and submaximal therapeutic doses of valproate was administered for 14days. Serum levels of valproate were estimated using HPLC for pharmacokinetic study. For pharmacodynamic interaction, antiepileptic effect on above seizure models, neurobehavioral effect using Morris water maze, passive avoidance and elevated plus maze tests, and antioxidant capacity were assessed. Ocimum sanctum hydroalcoholic extract 1000mg/kg was found to be optimal providing 50% protection against both MES- and PTZ-induced seizures. Combination of OSHE with valproate did not alter antiepileptic efficacy of valproate significantly. However, the combination showed better memory retention potential in neurobehavioral tests and protection against oxidative stress compared with valproate-alone-treated groups. Pharmacokinetic parameters did not reveal any significant change in combination group compared with valproate alone. Ocimum, although having per se antiepileptic action, did not affect antiepileptic action of valproate in combination. However, combination treatment has an edge over valproate alone-better neurobehavioral function and reduced oxidative stress-predicting adjuvant potential of Ocimum in epilepsy treatment.

Ethnopharmacological relevance Ocimum sanctum L. commonly known as tulsi (synonym of Ocimum tenuiflorum L.) is widely used in Ayurveda medicine and is having multitude neuromodulatory effect including the anticonvulsant effect in acute seizure models as per previous studies. In India, it is used for the treatment of epilepsy as traditional medicine. However, its role in chronic seizure model and interaction with newer antiepileptic drugs has not been investigated, which will enhance its translational value. Aim of the study Current study investigated the effect of Ocimum on chronic seizure model and its interaction with levetiracetam (LEV), a newer antiepileptic drug. Materials and methods The adjuvant role of Ocimum sanctum hydroalcoholic extracts (OSHE) 1000 mg/kg along with LEV 300 mg/kg was studied in adult male Wistar rats with mean weight of 227.84 ± 21.68 g using pentylenetetrazole (30 mg/kg, i.p.) kindling (K) (with maximum 24 injections on alternate days and challenge on 7th-day). Along with seizure score, neurobehavioral, brain tissue oxidative stress and histopathology status were assessed. Pharmacokinetic interaction was assessed between LEV and OSHE after 14 days of drug treatment. Results K-LEV + OSHE had least seizure score during kindling and on the pentylenetetrazole-challenge test (p=0.031) than other kindling groups. Seizure protection was more in K-LEV + OSHE (85.72%) than others (K-LEV-42.86%, K-OSHE-42.86%, and K-Control-28.58%). Ocimum treated groups had better memory retention potential as evident from Morris water maze (MWM), passive avoidance test but not in an elevated plus maze test. Oxidative-stress was lower in Ocimum treated groups than K-Control group. As per histopathology, K-LEV + OSHE group had the least neuronal degeneration among kindling groups. There was no significant pharmacokinetic interaction between LEV and OSHE, except increased Tmax in LEV + OSHE group than LEV alone (p=0.009). Conclusions Ocimum per se and combination with levetiracetam treatment exerted better seizure control, memory retention, oxidative stress reduction, and neuronal structure preservation than kindling control group. There was a very minimal drug interaction between Ocimum and LEV. So, Ocimum as an adjuvant to LEV may be shelpful in enhancing the antiepileptic effect and also in minimizing the adverse effects.

PurposeTherapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) in serum is frequently used in clinical settings however saliva could be an alternative to measure free concentration of drugs. In the present study, we observed the possible correlation of VPA concentration between serum and saliva in persons with epilepsy (PWE).MethodsA total of 59 paired serum and saliva samples were assayed from 65 consecutive PWE (51 males and 14 females; age range 9–65 years). Patients were subjected to either VPA monotherapy or its combination with other AEDs for at least three months. Steady state trough concentration of unbound VPA drug was quantified using HPLC. The correlation between serum and saliva free VPA concentration was evaluated.ResultsOut of 65 patients, 27 were on monotherapy of VPA and 38 were on VPA with other antiepileptic drugs. Saliva VPA concentration significantly correlated with serum free VPA concentration (p0.05) respectively.ConclusionsOur study reveals that serum and saliva VPA concentrations are significantly associated in PWE. These associations may facilitate monitoring and evaluation of VPA levels non-invasively for PWE.

Patients on dialysis have an increased incidence of tuberculosis (TB). Rifampicin, a first-line antitubercular therapy (ATT) drug, is a potent inducer of hepatic cytochrome P450 (CYP). There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP) was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP 50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001). Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46%) patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation.

There are conflicting reports in the literature about the influence of valproate on thyroid function. A cross-sectional study was performed to determine the prevalence of subclinical hypothyroidism in ambulatory children aged 3 to 15 years with controlled epilepsy receiving valproate monotherapy for at least 6 months. Fifty-seven consecutive children with controlled epilepsy on valproate monotherapy and 52 healthy age- and sex-matched control children were studied. Thyroid-stimulating hormone, free thyroxine, antithyroid peroxidase antibodies, and serum valproic acid levels were measured. There was a significantly high ( P = .012) prevalence of subclinical hypothyroidism (26%) in those receiving valproate monotherapy compared with healthy controls (7.7%). Median duration of valproate therapy was significantly higher ( P = .039) in the subclinical hypothyroidism group (21 months, range 6-36) compared with those without subclinical hypothyroidism (14 months, range 6-25). Results of the present study suggest higher prevalence of subclinical hypothyroidism in children with controlled epilepsy on long-term valproate monotherapy.

The monitoring of antiepileptic drugs (AEDs) in clinical setting is important for measuring the efficacy of drugs and their safety and in personalizing drug therapy. We investigated the levels of AED, carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PHB), to understand their association in saliva compared with those in serum during the therapy.In this study, we performed a prospective study of 116 persons with epilepsy (PWE; mean age 26.90 ± 11.83 years). Serum and saliva samples were collected at trough levels from the patients, who were under the treatment of CBZ, PHT and PHB either alone or in combination of these drugs for at least three months. The drug levels were assessed by high-performance liquid chromatography.The number of males (n = 88; 75.86%) was higher than females (n = 28; 24.14%) among the recruited patients. The intake of CBZ, PHT and PHB was observed in 49.14%, 68.10% and 38.79% of PWE, respectively. The levels of these AEDs showed a significant correlation (p0.05) between serum and saliva. Interestingly, the levels of mono-therapy or bi-therapy showed a significant association (p0.05) between serum and saliva, however, there was no significant association in case of poly-therapy. This is the first report in the Indian population on simultaneous estimation of the three commonly used AEDs, such as CBZ, PHT and PHB in serum and saliva implicating their associations, either in mono-therapy or bi-therapy in PWE.

A retrospective analysis of the poisoning calls received by the National Poisons Information Centre (NPIC) showed a total of 2,720 calls during a period of three years (April 1999-March 2002). Poisoning in children was reported in 995 calls (36.6%). The age ranged from less than 1 yr to 18 yr and the age groups involved were divided into four categories (0-6 yr, >6-12 yr, >12-16 yr, >16-18 yr). The most vulnerable age group included children from less than one year to 6 yr old. Males outnumbered females (M=628, F=367). Although the accidental mode was the commonest (79.7%), intentional attempts were also noticed (20.2%) in the >12-16 yr and >16-18 yr age groups. In the majority of cases, the route was oral (96.8%) followed by dermal exposure (3.2%) comprising bites and stings. Various types of agents belonged to classes of household products (47.0%), drugs (21.8%), industrial chemicals (7.9%), agricultural pesticides (9.1%), bites and stings (3.2%), plants (1.5%), miscellaneous products (5.3%) and unknown products (4.0%). The incidence of poisoning was highest due to household products comprising mainly pyrethroids, parad/thermometer mercury, rodenticides, phenyl, detergents and corrosives, etc. Poisoning due to drugs mainly included anticonvulsants, thyroid hormones, benzodiazepines, analgesics and oral contraceptives. Among the agricultural pesticides aluminium phosphide was the most commonly consumed, followed by organochlorines and organophosphates, etc. Paint thinners were common among industrial chemicals. Bites and stings were mainly snake bites and scorpion stings. Poisoning due to plants was low and Datura was commonly ingested. Although these data may not give an exact picture of the incidence rate in our country, due to underreporting of calls to the Centre and because the actual incidence might be higher or even variable, but they do give the trend in India, indicating that a strong emphasis should be placed on a prevention campaign which can at least reduce the occurrence of accidental pediatric poisoning.

Screening for corticosteroids carried out on 120 samples of alternative medicines which were dispensed to patients suffering mainly from asthma, arthritis, etc., showed that 38.32% of them were adulterated with steroids. Most of these samples were submitted for screening by either a medical practitioner or the patients themselves, who suspected effects of steroids from these drugs. The percentage of steroid positivity was determined in ayurvedic drugs, homeopathic drugs, and unknown or other category of drugs. The presence of steroids in these drugs given for different ailments such as asthma, arthritis, and unknown/other ailments was also tabulated. The results show that a high percentage of these samples contained corticosteroids, however, the distribution of positivity amongst groups was not statistically significant. The lack of proper quality control mechanisms to verify ingredients or efficacy of 'alternative medicines' has led to the proliferation of the practice of dispensing spurious drugs containing corticosteroids as alternative medicines. This study aims to highlight the existence of 'quick fix' remedies dispensed as 'alternative medicines' which not only cause extensive adverse health effects to the patients but also bring alternative systems of medicines into disrepute. The deliberate contamination of corticosteroids with alternative systems of medicine by some practitioners is a cause of great concern. Such practices may not only disgrace alternative systems of medicine but may also lead to adverse side-effects on chronic exposure.

Severe sepsis is common and often fatal. The expanding armamentarium of evidence-based therapies has improved the outcomes of persons with this disease. However, the existing national estimates of the frequency and outcomes of severe sepsis were made before many of the recent therapeutic advances. Therefore, it is important to study the outcomes of this disease in an aging US population with rising comorbidities.We used the Healthcare Costs and Utilization Project's Nationwide Inpatient Sample (NIS) to estimate the frequency and outcomes of severe sepsis hospitalizations between 2000 and 2007. We identified hospitalizations for severe sepsis using International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating the presence of sepsis and organ system failure. Using weights from NIS, we estimated the number of hospitalizations for severe sepsis in each year. We combined these with census data to determine the number of severe sepsis hospitalizations per 100,000 persons. We used discharge status to identify in-hospital mortality and compared mortality rates in 2000 with those in 2007 after adjusting for demographics, number of organ systems failing, and presence of comorbid conditions.The number of severe sepsis hospitalizations per 100,000 persons increased from 143 in 2000 to 343 in 2007. The mean number of organ system failures during admission increased from 1.6 to 1.9 (P.001). The mean length of hospital stay decreased from 17.3 to 14.9 days. The mortality rate decreased from 39% to 27%. However, more admissions ended with discharge to a long-term care facility in 2007 than in 2000 (35% vs 27%, P.001).An increasing number of admissions for severe sepsis combined with declining mortality rates contribute to more individuals surviving to hospital discharge. Importantly, this leads to more survivors being discharged to skilled nursing facilities and home with in-home care. Increased attention to this phenomenon is warranted.

Chronic obstructive pulmonary disease (COPD) is a prevalent progressive condition that adversely affects quality of life and sleep. Patients with COPD suffer from variety of sleep disorders including insomnia, sleep disordered breathing and restless leg syndrome. The sleep disorders in COPD patients may stem from poor control of primary disease or due to side effects of pharmacotherapy. Thus, optimization of COPD therapy is the main step in treating insomnia in these patients. Further, pharmacotherapy of sleep disorders may result in respiratory depression and related complications. Therefore, clear understanding of respiratory physiology during transition from wakefulness to sleep and during various stages of sleep plays an important role in therapies that are recommended in patients with significant airway obstruction. In this publication, we review respiratory physiology as it relates to sleep and discuss sleep disorders and their management in patients with COPD.

Background: Valproate is a commonly used anticonvulsant drug. Uridine 5΄-diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of valproate metabolism and its polymorphisms may be important for explaining the considerable variation in valproate levels in patients with epilepsy. Aim: This study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and their potential influence on the pharmacokinetics of valproate. Setting and Design: This cross-sectional study was carried out in the Department of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi, between March 2011 and July 2012. Materials and Methods: Children aged 3-12 years diagnosed with epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination. The UGT1A6 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Random samples were checked by genetic sequencing. The steady-state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms. Results: A total of 80 children were studied. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes could not be studied reliably in this small study population. Conclusions: The frequencies of UGT1A6 geneotypes and alleles were reported in the study population.

A retrospective analysis of poisoning calls received by the National Poisons Information Centre showed a total of 2719 calls over a period of three years (April 1999-March 2002). The queries were made on poisoning management (92%) and information (8%) about various products and functioning of the centre. The data were analysed with respect to age, sex, mode and type of poisoning. The agents belonged to various groups: household products, agricultural pesticides, industrial chemicals, drugs, plants, animal bites and stings, miscellaneous and unknown groups respectively. The age ranged from less than 1 to 70 years, with the highest incidence in the range of 14-40 years, with males (57%) outnumbering females (43%). The most common mode of poisoning was suicidal (53%), followed by accidental (47%). The route of exposure was mainly oral (88%). Dermal (5%), inhalation and ocular exposure contributed 7% to the total. The highest incidence of poisoning was due to household agents (44.1%) followed by drugs (18.8%), agricultural pesticides (12.8%), industrial chemicals (8.9%), animals bites and stings (4.7%), plants (1.7%), unknown (2.9%) and miscellaneous groups (5.6%). Household products mainly comprised of pyrethroids, rodenticides, carbamates, phenyl, detergents, corrosives etc. Drugs implicated included benzodiazepines, anticonvulsants, analgesics, antihistamines, tricyclic antidepressants, thyroid hormones and oral contraceptives. Among the agricultural pesticides, aluminium phosphide was the most commonly consumed followed by organochlorines, organophosphates, ethylene dibromide, herbicides and fungicides. Copper sulphate and nitrobenzene were common among industrial chemicals. The bites and stings group comprised of snake bites, scorpion, wasp and bee stings. Poisoning due to plants was low, but datura was the most commonly ingested. An alarming feature of the study was the high incidence of poisoning in children (36.5%). The age ranged from less than 1 to 18 years and the most vulnerable age group included children from less than 1 year to 6 years. Accidental mode was the most common (79.7%). Intentional attempts were also noticed (20.2%) in the age group above 12 years. The present data may not give an exact picture of the incidence of poisoning in India, but represents a trend in our country. The Poisons Information Centre plays a vital role in providing timely management guidelines including the supply of necessary antidotes from the recently established National Antidote Bank, thereby helping to save precious lives.