The placenta as a target of opioid drugs

Opioid drugs are analgesics increasingly being prescribed to control pain associated with a wide range of causes. Usage of pregnant women has dramatically increased in the past decades. Neonates born to these women are at risk for neonatal abstinence syndrome (NAS, also referred termed neonatal opioid withdrawal syndrome, NOWS). Negative birth outcomes linked with maternal opioid use disorder include compromised fetal growth, premature birth, reduced birthweight, and congenital defects. Such infants require lengthier hospital stays necessitating rising health care costs, and they are at greater risk for neurobehavioral and other diseases. Thus, it is essential to understand the genesis of such disorders. As the primary communication organ between mother and conceptus, the placenta itself is susceptible to opioid effects but may be key to understanding how these drugs affect long-term offspring health and how poor health outcomes may be ameliorated in utero. In this review, we will consider the evidence that placental responses are regulated through an endogenous opioid system. However, maternal consumption of opioid drugs can also bind and act through opioid receptors express by trophoblast (TB) cells of the placenta. Thus, we will also discuss the current human and rodent studies that have examined the effects of opioids on the placenta. These drugs might affect placental hormones associated with maternal recognition of pregnancy, including placental lactogens and human chorionic gonadotropin (hCG) in rodents and humans, respectively. A further understanding of how such drugs affect the placenta may open up new avenues for early diagnosis and remediation approaches.

Remdesivir and dexamethasone as tools to relieve hospital care systems stressed by COVID-19: A modelling study on bed resources and budget impact

Remdesivir and dexamethasone are the only drugs providing reductions in the lengths of hospital stays for COVID-19 patients. We assessed the impacts of remdesivir on hospital-bed resources and budgets affected by the COVID-19 outbreak. A stochastic agent-based model was combined with epidemiological data available on the COVID-19 outbreak in France and data from two randomized control trials. Strategies involving treating with remdesivir only patients with low-flow oxygen and patients with low-flow and high-flow oxygen were examined. Treating all eligible low-flow oxygen patients during the entirety of the second wave would have decreased hospital-bed occupancy in conventional wards by 4% [2%; 7%] and intensive care unit (ICU)-bed occupancy by 9% [6%; 13%]. Extending remdesivir use to high-flow-oxygen patients would have amplified reductions in ICU-bed occupancy by up to 14% [18%; 11%]. A minimum remdesivir uptake of 20% was required to observe decreases in bed occupancy. Dexamethasone had effects of similar amplitude. Depending on the treatment strategy, using remdesivir would, in most cases, generate savings (up to 722€) or at least be cost neutral (an extra cost of 34€). Treating eligible patients could significantly limit the saturation of hospital capacities, particularly in ICUs. The generated savings would exceed the costs of medications.

Bacterial and fungal co-infections among ICU COVID-19 hospitalized patients in a Palestinian hospital: a retrospective cross-sectional study

Background: Diagnosis of co-infections with multiple pathogens among hospitalized coronavirus disease 2019 (COVID-19) patients can be jointly challenging and essential for appropriate treatment, shortening hospital stays and preventing antimicrobial resistance. This study proposes to investigate the burden of bacterial and fungal co-infections outcomes on COVID-19 patients. It is a single center cross-sectional study of hospitalized COVID-19 patients at Beit-Jala hospital in Palestine. Methods: The study included 321 hospitalized patients admitted to the ICU between June 2020 and March 2021 aged ≥20 years, with a confirmed diagnosis of COVID-19 via reverse transcriptase-polymerase chain reaction assay conducted on a nasopharyngeal swab. The patient's information was gathered using graded data forms from electronic medical reports. Results: The diagnosis of bacterial and fungal infection was proved through the patient’s clinical presentation and positive blood or sputum culture results. All cases had received empirical antimicrobial therapy before the intensive care unit (ICU) admission, and different regimens during the ICU stay. The rate of bacterial co-infection was 51.1%, mainly from gram-negative isolates (Enterobacter species and K.pneumoniae). The rate of fungal co-infection caused by A.fumigatus was 48.9%, and the mortality rate was 8.1%. However, it is unclear if it had been attributed to SARS-CoV-2 or coincidental. Conclusions: Bacterial and fungal co-infection is common among COVID-19 patients at the ICU in Palestine, but it is not obvious if these cases are attributed to SARS-CoV-2 or coincidental, because little data is available to compare it with the rates of secondary infection in local ICU departments before the pandemic. Comprehensively, those conclusions present data supporting a conservative antibiotic administration for severely unwell COVID-19 infected patients. Our examination regarding the impacts of employing antifungals to manage COVID-19 patients can work as a successful reference for future COVID-19 therapy.

The Effectiveness of a Diverse COVID-19 Vaccine Portfolio and Its Impact on the Persistence of Positivity and Length of Hospital Stays: The Veneto Region’s Experience

The vaccination campaign for the Veneto region (northeastern Italy) started on 27 December 2020. As of early December 2021, 75.1% of the whole Veneto population has been fully vaccinated. Vaccine efficacy has been demonstrated in many clinical trials, but reports on real-world contexts are still necessary. We conducted a retrospective cohort study on 2,233,399 residents in the Veneto region to assess the reduction in the COVID-19 burden, taking different outcomes into consideration. First, we adopted a non-brand-specific approach borrowed from survival analysis to estimate the effectiveness of vaccination against SARS-CoV-2 in preventing infections, hospitalizations, and deaths. We used t-tests and multivariate regressions to examine vaccine impact on breakthrough infections, in terms of the persistence of positivity and the length of hospital stays. Evidence emerging from this study suggests that unvaccinated individuals are significantly more likely to become infected, need hospitalization, and are at a higher risk of death from COVID-19 than those given at least one dose of vaccine. Cox models indicate that the effectiveness of full vaccination is 88% against infection, 94% against hospitalization, and 95% against death. Multivariate regressions suggest that vaccination is significantly correlated with a shorter period of positivity and shorter hospital stays, with each step toward completion of the vaccination cycle coinciding with a reduction of 3.3 days in the persistence of positivity and 2.3 days in the length of hospital stay.

Functional outcomes in children related to self-care, mobility, and social function after stroke in early childhood: a cohort study

ABSTRACT Background: Stroke has been increasingly recognized as an important morbidity and mortality factor in neonates and children. Children have different and more diverse risk factors than adults, commonly related to an underlying disease. Stroke may compromise functional capacity in children. Few studies have focused on functional outcomes related to activities and participation. Objectives: To investigate post-stroke functionality of children related to self-care, mobility, and social function. Methods: We assessed the functional outcome of 14 children younger than 7.5 years who suffered a stroke in early childhood through the use of the Pediatric Evaluation of Disability Inventory (PEDI). Results: The average age of the sample at assessment was 3.6 ± 1.4 years (2 - 6 years). The average scores in the PEDI functional domains of self-care, mobility, and social function were, respectively, 37.6 ± 15.4, 36.2 ± 15.4, and 48.7 ± 11.1. Children showed age-appropriate functional outcomes in the PEDI functional domains: 71.4% of them in self-care and mobility and 92.9% in social function. Children with bilateral injuries (p = 0.05) and longer hospital stays (r = -0.79, p = 0.001) showed the worst scores in PEDI's social function domains. Conclusions: Overall, our sample of preschool children showed age-appropriate functional outcomes on self-care, mobility, and social function domains after stroke. However, children with bilateral injuries and longer hospital stays showed the worst scores in social function domains. We recommend focusing on functional rehabilitation to promote activities and participation and to monitor the development of children's social skills after stroke.

Intentional Fallers with Complex Pelvic and Acetabular Fractures Do Not Have worse Radiological and Functional Outcomes than Accidental Fallers

Individuals who fall from heights of ≥6 m can suffer from complex pelvic and acetabular fractures. The extent to which an intentional fall correlates with prognosis and outcome after osteosynthesis is unclear. Therefore, we aimed to investigate the clinical outcomes of fallers with pelvic and acetabular fractures after osteosynthesis and compare the radiological and functional outcomes between intentional and accidental fallers. We retrospectively reviewed 49 fallers who fell from heights of ≥6 m, developed pelvic and acetabular fractures, survived after resuscitation, and completed surgical treatment between 2014 and 2017. Fallers were divided into intentional and accidental fallers. Sixteen patients were intentional fallers, whereas the rest of the patients were accidental fallers. Psychiatric counseling was provided to each of the intentional fallers during follow-up. All intentional fallers had preexisting mental disorders, and the most common diagnosis was adjustment disorder. The group of intentional fallers predominantly comprised females that had a higher injury and new injury severity scores and longer hospital stays. However, early loss of fixation (<3 months) and functional outcomes (Merle d’Aubigné and Majeed hip scores at 6- and 12-month follow-ups) did not significantly differ between intentional and accidental fallers. We found that intentional fallers with pelvic and acetabular fractures may have more severe combined injuries compared to accidental fallers. However, the radiological and functional outcomes of the intentional fallers after osteosynthesis were not inferior to those of the accidental fallers with the implementation of well-designed surgical protocols and individualized physical and mental rehabilitation programs.

U-Shape Relationship between Plasma Leucine Level and Mortality in the Intensive Care Unit

Patients in the intensive care unit (ICU) are at high risk of mortality which is not well predicted. Previous studies noted that leucine has prognostic value in a variety of diseases. This study investigated whether leucine concentration was a useful biomarker of metabolic and nutritional status and 6-month mortality in ICU. We recruited 454 subjects admitted to ICU (348 and 106 in the initiation and validation cohorts, respectively) with an acute physiology and chronic health evaluation (APACHE II) score ≥ 15 . We measured plasma leucine concentrations, traditional biomarkers, and calculated APACHE II and sequential organ failure assessment (SOFA) scores. Leucine levels were weakly correlated with albumin, prealbumin, and transferrin levels ( r = 0.30 , 0.12, and 0.15, p = 0.001 , 0.029, and 0.007, respectively). During follow-up, 116 (33.3%) patients died. Compared to patients with leucine levels between 109 and 174 μM, patients with leucine > 174 μ M or <109 μM had a lower cumulative survival rate. Death was also associated with age, higher APACHE II and SOFA scores, C-reactive protein, and longer stays in the ICU, but with lower albumin, prealbumin, and transferrin. Patients with leucine levels > 174 μ M had higher alanine aminotransferase levels, but no significant differences in other variables; patients with leucine levels < 109 μ M had higher APACHE II and SOFA scores, higher incidence of using inotropic agents, longer ICU and hospital stays, but lower albumin and transferrin levels. Multivariable analysis demonstrated that leucine > 174 μ M was an independent predictor of mortality, especially early mortality. However, among patients who stayed in ICU longer than two weeks, leucine < 109 μ M was an independent predictor of mortality. In addition, leucine < 109 μ M was associated with worse ventilator weaning profiles. These findings were similar in the validation cohort. Our study demonstrated a U-shape relationship between leucine levels and mortality rate in ICU.

Determinants of COVID-19-Related Length of Hospital Stays and Long COVID in Ghana: A Cross-Sectional Analysis

Objectives: There is paucity of data on determinants of length of COVID-19 admissions and long COVID, an emerging long-term sequel of COVID-19, in Ghana. Therefore, this study identified these determinants and discussed their policy implications. Method: Data of 2334 patients seen at the main COVID-19 treatment centre in Ghana were analysed in this study. Their characteristics, such as age, education level and comorbidities, were examined as explanatory variables. The dependent variables were length of COVID-19 hospitalisations and long COVID. Negative binomial and binary logistic regressions were fitted to investigate the determinants. Result: The regression analyses showed that, on average, COVID-19 patients with hypertension and diabetes mellitus spent almost 2 days longer in hospital (p = 0.00, 95% CI = 1.42–2.33) and had 4 times the odds of long COVID (95% CI = 1.61–10.85, p = 0.003) compared to those with no comorbidities. In addition, the odds of long COVID decreased with increasing patient’s education level (primary OR = 0.73, p = 0.02; secondary/vocational OR = 0.26, p = 0.02; tertiary education OR = 0.23, p = 0.12). Conclusion: The presence of hypertension and diabetes mellitus determined both length of hospitalisation and long COVID among patients with COVID-19 in Ghana. COVID-19 prevention and management policies should therefore consider these factors.

Lumboperitoneal Shunt Surgery Under Rachianesthesia

Purpose: In the very elderly, complications such as postoperative pneumonia or delirium, which are directly associated with longer hospitalization, are more frequent. In order to overcome these drawbacks, we switched from general anesthesia to rachianesthesia for the lumboperitoneal shunt (LPS) procedure in idiopathic normal pressure hydrocephalus (iNPH) patients. This is because iNPH suffers particularly elderly patients, and neuraxial anesthesia techniques such as rachianesthesia reportedly decrease postoperative complications in patients of very advanced age as compared with general anesthesia. Methods: We retrospectively analyzed 45 patients who underwent LPS in our institution, and divided them into two groups based on the anesthetic approach; 1) general anesthesia, 2) rachianesthesia. We analyzed these two groups with regard to postoperative delirium score and the hospital stay.Results: In the general anesthesia group, two patients had respiratory complications after the surgery. The mean postoperative delirium score using the intensive care delirium screening checklist (ICDSC) was 1.3 (1.4) and the length of hospital stay was 13.9 (4.7) days. In the rachianesthesia group, no patients had respiratory complications. The postoperative mean ICDSC was 1.3 (1.4), and the length of hospital stay was 10.8 (2.1) days. The statistical analysis showed the rachianesthesia group to have significantly shorter hospital stays.Conclusions: LPS under rachianesthesia is an alternative to performing this procedure under general anesthesia in elderly patients.

Developing a Quality Improvement Feeding Program for NICU Patients

Practices in NICUs vary widely, particularly when clinical decisions involve complex tasks and multiple disciplines, which occurs with feeding preterm infants. Neonatal feeding difficulties in preterm infants often lead to prolonged tube feeding and therefore lengthened hospital stays. Education and compliance with evidence-based protocols and guidelines are needed on the initiation of feedings and feeding advancement to transform enteral and oral feeding practices and thus reduce practice variation and improve clinical outcomes.