Absence Of Death Research Articles

Disparity in oncology therapy access and differences in clinical pathological features and outcomes in indigenous population lung cancer (LC): A retrospective study from Martinique.

1599 Background: The epidemiology of cancers in terms of incidence and mortality are different in the French overseas compared to mainland France (FRANCIM 2019 data). Indigenous population are under-represented in clinical trials. Little is known about clinic-pathological features and outcomes from Caribbean islands. We report clinico-pathological features and survival in populations of patients with lung cancer (LC) and delays in access to therapy in Martinique. Methods: We conducted an academic retrospective study on patients with lung cancer (LC), treated at the University Hospital in Martinique between 2020-2022. The hospital in Martinique centralized all cancer patients in the territory for treatment. Demographic, risk factors, disease features, and treatment outcomes were collected from medical records. The molecular profile was determined using next-generation sequencing with the Archer FUSION Plex Lung v2 panel, evaluating at least EGFR, ALK, KRAS, ERBB2, MET, ROS1, BRAF, RET, NUTM1, PIK3CA, FGFR1, FGFR2, FGFR3, NRG1, NTRK1, NTRK2, NTRK3. We assessed time from symptoms to diagnosis and treatment, and overall survival (OS). Results: Overall, 268 patients (pts) were included. Pts were male in 51% cases (N=136), had a smoking history in 57% (N=139/243), with a median pack-years of 40 [IQR 22-50]. Median age was 67 years-old [IQR 58-78]. Histology was adenocarcinoma in 78% (N = 208), squamous cell in 13% (N=34), neuroendocrine tumors in 8% (N=21), and others in 2% (N=5). No small cell carcinoma diagnosed. Tumors had high PD-L1 expression (≥50%) in 18% (N=41/227) of cases. An oncogenic addiction was reported in 58% (N =105/181) of non-small cell and non-squamous lung carcinoma: EGFR36% (N=65), ALK3.3% (N=6), BRAF1.1% (N=2), KRAS13.3% (N=24). Pts had an ECOG performance status of 0-1 at diagnosis in 66% (N =162/244). LC was metastatic from diagnosis in 65% cases (N=175), with 18% having brain metastases (N=48). Median time between symptom occurrence and diagnosis was 66 days [IQR 21-171] and time between biopsy and treatment start was 56 days [IQR 31-77]. In pts with stage IV disease, 33% (N=59/175) never received a systemic treatment. In patients with at least 6 months of follow-up in the absence of death, median OS was 12.4 months (95% CI 8.6 – 17.1) overall and 8.6 months (95% CI 5.3 – 13.3) in patients with initial metastases. Conclusions: The lower overall survival rate than expected in this cancer context address the question of disparity population. One-third of LC metastatic patients did not receive systemic therapy. The local inadequacy of care pathways, leading to disparities in access to imaging, may explain the delays and poorer prognosis. A new initiative from a collaborative group with health authorities, caregivers, politicians and patient’s advocacy is actively working to improve cancer patient’s outcomes.

Predicting Mortality Risks Using Body Mass Index and Weight Loss at Admission in Patients with Heart Failure.

The association of the combination of body mass index (BMI) and weight change at admission with prognoses in patients with heart failure (HF) is unclear. Therefore, we investigated whether BMI and weight changes at admission affect mortality in patients with HF. This retrospective cohort study lasted 99 months, starting in April 2014, and included 4,862 patients with HF from a Japanese real-world database. Cubic and thin-plate smoothing spline analyses were performed to investigate the association of BMI and weight changes with mortality. The percentage weight change was calculated every 6 months. The study outcome was the presence or absence of death. The patients' mean age was 81.5±9.6 years, and 1,239 (25.5%) patients died. Cubic spline analysis revealed a negative correlation of BMI with mortality hazard ratio (HR) (BMI of 18.5 kg/m2 and 25 kg/m2; HR=1.3 [1.2-1.4] and 0.8 [0.7-0.9], respectively). Cubic spline analysis of weight change showed that weight loss tended to increase the mortality HR (each 6% decrease in weight change rate was associated with a 1.1 times higher mortality risk (95% CI [1.0-1.2]) Thin-plate smoothing spline analysis showed that the odds ratio (OR) negatively correlated with BMI (1-year mortality: BMI of 18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.5, 1.0, and 0.7, respectively; 2-year mortality: BMI=18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.4, 0.9, and 0.7, respectively). A low BMI in patients with HF was associated with a higher risk of mortality. Weight loss in patients, regardless of BMI, was associated with a higher OR for mortality.

Mourning revolutions in the virtual anastasis

Mourning Revolutions in the Virtual Anastasis is a psychoanalytical and philosophical analysis, that places contemporary technologies and emerging practices for digital and virtual mourning into conversation with Freudian, Jungian, and Lacanian concepts. Through a series of speculations, the text wants to scrutinise the motives behind today's simulative technologies and hypothesise about the future interrelation between the individual and the absence of death. Although the argument is presented by clearly assuming a contrasting position to the use of VR high-tech novelties, the aim is still to offer a point of reflection rather than imposing a unilateral perspective. Therefore, the emphasis is placed on the multifaceted instances of virtually resurrecting loved ones and the inevitable revolutions that will be carried within the mourning process, ultimately departing from orthodox psychological views. The impacts of these revolutions are still largely obscure, but some light will be thrown by examining the internal dynamics of the individual mind and society as a whole. It will be argued how technological advancements, habitually embraced as a sign of evolution, contextualised within the main argumentation, hold a significant risk of being just an illusion of progress: a social regressive phenomenon in its enactment of unconscious fixations. Moreover, thought-provoking claims challenging the psychosocial institutions are delivered to unfold the ethical and political dynamics, particularly concerning psychoanalysis. The reader might find the role of the latter devalued in the critique engaged, in truth, the concluding argumentation is almost an ode to the practice by expressing the hope that by abandoning its tight conservative frame, such an essential tool of analysis will maintain its relevance in the 21st century. The conclusion of such an adventurous exploration will propose psychoanalysis as philosophy with a clinic.

“They talked to me rudely”. Women perspectives on quality of post-abortion care in public health facilities in Kenya

BackgroundAccess to safe abortion is legally restricted in Kenya. Therefore, majority women seeking abortion services in such restrictive contexts resort to unsafe methods and procedures that result in complications that often require treatment in health facilities. Most women with abortion-related complications end up in public health facilities. Nevertheless, evidence is limited on the quality of care provided to patients with abortion complications in public health facilities in Kenya.MethodsData for this paper are drawn from a qualitative study that included interviews with 66 women who received post-abortion care in a sample of primary, secondary and tertiary public health facilities in Kenya between November 2018 and February 2019. The interviews focused on mechanisms of decision-making while seeking post-abortion care services, care pathways within facilities, and perceptions of patients on quality of care received including respect, privacy, confidentiality, communication and stigma.FindingsThe participants’ perceptions of the quality of care were characterized as either “bad care” or “good care”, with the good care focusing on interpersonal aspects such as friendliness, respect, empathy, short waiting time before receiving services, as well as the physical or functional aspects of care such as resolution of morbidity and absence of death. Majority of participants initially reported that they received “good care” because they left the facility with their medical problem resolved. However, when probed, about half of them reported delays in receiving care despite their condition being an emergency (i.e., severe bleeding and pain). Participants also reported instances of abuse (verbal and sexual) or absence of privacy during care and inadequate involvement in decisions around the nature and type of care they received. Our findings also suggest that healthcare providers treated patients differently based on their attributes (spontaneous versus induced abortion, single versus married, young versus older). For instance, women who experienced miscarriages reported supportive care whereas women suspected to have induced their abortions felt stigmatized.ConclusionThese findings have far reaching implications on efforts to improve uptake of post-abortion care, care seeking behaviors and on how to assess quality of abortion care. There should be emphasis on interventions meant to enhance processes and structural indicators of post-abortion care services meant to improve patients’ experiences throughout the care process. Moreover, more efforts are needed to advance the tools and approaches for assessing women experiences during post-abortion care beyond just the overriding clinical outcomes of care.

Pressure cooker technique in cerebral AVMs and DAVFs: different treatment strategies.

The pressure cooker technique (PCT) was developed to enable safer and more extensive embolization of hypervascular lesions by simultaneously minimizing backflow of liquid embolic materials and thus reduce the risk of non-target embolization of adjacent healthy vessels. We report our experience in applying the PCT to cerebral arteriovenous malformations (AVMs) and dural arteriovenous fistulas (DAVFs) and additionally suggest our technical adjustments. We retrospectively reviewed all patients suffering from AVMs or DAVFs that were treated with the PCT between 2018 and 2020 in two university hospitals. The endpoints of the study were clinical safety and the technical efficacy. The endpoints of the study were clinical safety and the technical efficacy. Clinical safety was the absence of death, major or minor symptomatic stroke, TIA and procedure-related intracranial bleeding (SAH) in the peri-procedural period until dismission. Good clinical outcome was defined as no deterioration of the modified Rankin Scale (mRS) score (comparing the pre- and post-procedural mRS evaluated by a trained neurologist at admission and dismission). The technical efficacy was considered as the complete embolization occlusion of the target vessels of the lesion documented on the final control angiogram. Long-term follow-up evaluation was not intended for this study as it was not available for all patients. Fifteen consecutive patients (6 women; mean age 55 y; range 20-82 y) with seven AVMs and eight DAVFs met the inclusion criteria. The primary clinical safety end point was obtained in all cases as no intraprocedural complications were encountered. All patients had a good clinical outcome with no difference between the pre- and post-mRS scores. The primary efficacy end point was reached in all cases. The PCT is a safe and effective technique in the treatment of cerebral AVMs and DAVFs. Adding an easy and fast step to the procedure, namely the injection of contrast media to test the complete obstruction by the plug, the risk of reflux seems to additionally be reduced.

Acute and developmental toxicity of embelin isolated from Embelia schimperi Vatke fruit: In vivo and in silico studies.

Embelin is a hydroxybenzoquinone constituent of the Embelia species that has anti-disease properties. However, its toxicity, particularly the in silico, acute, and developmental toxicity profiles, has yet to be thoroughly investigated. Hence, this study aims to assess these toxicity profiles. In silico and in vivo experimental studies were conducted on embelin isolated from the fruits of Embelia schimperi Vatke. In silico toxicity predictions were computed using the ProTox model. The in vivo experiment was done by administering 5000mg/kg of embelin to a single female albino Wistar rat, followed by three female rats in the absence of death, to determine the mean lethal dose (LD50). Afterwards, three groups of pregnant rats were treated with embelin at doses of 250mg/kg, 500mg/kg, and 1000mg/kg for the developmental toxicity test. Vehicle and ad libitum control groups were used to compare the acute and developmental toxicity variables. In silico toxicity predicted that embelin is free from hepatotoxic, carcinogenic, mutagenic, and cytotoxic effects. No inhibitory effect on hERG channels was observed. It has an immunotoxic property and an inhibitory effect on the CYP2D6 enzyme. Since mortality and signs of toxicities were not observed after treatment with 5000mg/kg, the mean lethal dose (LD50) is determined to be >5000mg/kg. There was no significant difference in the morphological scores or number of somites among experimental animals. None of the embryonic systems possessed developmental delays. Nevertheless, the crown-rump length of the high-dose group became significantly shorter. Maternal food intake and weight gain exhibited significant dose-dependent differences between embelin-treated animals and controls. The number of implantations was significantly low in the treatment group, accompanied by a higher frequency of prior resorption. Embelin is predicted to have a high probability of immunotoxicity potential and affect drug metabolism by inhibiting CYP2D6. In addition, it affects food intake, weight gain, and the number of implantations in pregnant rats. Therefore, it is highly recommended not to take embelin and embelin-rich plants during pregnancy. Further in vitro and in vivo studies need to be conducted to understand the mechanism behind the toxicity of embelin.

Toxicity test of gelatin capsule materials from pangasius skin (Pangasius sp.) on mice (Mus musculus)

Gelatin is produced from animal skin and bones, which can be used as an ingredient in medicine capsules. There are issues regarding the mad cow disease and certain religious rules that do not allow the consumption of gelatin from pigs and cows, opening up opportunities for developing gelatin derived from fish. This study aims to determine the level of toxicity of pangasius skin gelatin capsules (Pangasius sp.) using the fixed-dose procedure method in mice based on the LD50 value. The 2,000 mg/kg BW dose is determined as the initial dose of the main test after the preliminary test. The test animals were divided into 2 groups, each containing 5 female mice of the DDY strain. The first group was the control group, and the second group was the test animal group which was treated with a dose of 2,000 mg/kg BW. The results showed that the LD50 value of pangasius skin gelatin was > 2,000 mg/kg BW. Pangasius skin gelatin is not toxic, as evidenced by the absence of death and changes in the average body weight of mice. Based on the significant difference in relative weight, only the lungs were affected by pangasius skin gelatin.

Flow Diverting Stents in Cerebral Small Caliber Vessels (< 2 mm) for Aneurysm Treatment : AThree Center Retrospective Study.

The off-label use of flow diverting stents (FDS) for treating cerebral aneurysms in small distal vessels is increasing in clinical practice with encouraging results; however, data directly addressing the parent vessel size are still scarce. Our aim was to evaluate the safety and efficacy of FDS placement in anterior and posterior circulation aneurysms with parent arteries ≤ 2 mm in areal-world representative setting. We retrospectively reviewed patients treated with FDS at the three participating university hospitals between 2009 and 2021. The inclusion criteria were the placement of at least one FDS in aparent vessel with amaximum diameter of 2 mm or less. The primary clinical safety endpoint was the absence of death, major or minor symptomatic stroke, transient ischemic attack and procedure-related intracranial hemorrhage. Clinical outcome was assessed using the modified Rankin Scale (mRS) score at the follow-up visit at 1year. The primary efficacy endpoint was defined as complete and near-complete occlusion at the 1‑year follow-up. We identified 55patients harboring 56aneurysms. The primary clinical safety endpoint was obtained in 93% of cases. The hemorrhagic and thromboembolic complication rates were 4% and 9%, respectively. No patient died or had arelevant discrepancy (> 1point) at the pre-mRS and post-mRS. The primary efficacy endpoint was reached in 80% of cases. The use of FDS in vessels < 2 mm is technically feasible with good aneurysm occlusion rates and an acceptable safety profile. Nevertheless, it is essential to be aware of the of the main complications associated when operating in small diameter vessels.

Costus spiralis extract restores kidney function in cisplatin-induced nephrotoxicity model: Ethnopharmacological use, chemical and toxicological investigation

Ethnopharmacological relevanceCostus spiralis (Jacq.). Roscoe (Costaceae) is traditionally used in Brazil for the treatment of kidney diseases such as pyelonephritis, urethra inflammation, kidney stones, and inflammatory conditions. There are reports of its use by Brazilian Indians since the 17th century when it was known as “pacocatinga.” Currently, the use of the Costus species in Brazil is widespread, which was evidenced by the inclusion of the genus in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). Aim of the studyThis study aimed to confirm the ethnopharmacological use of Costus spiralis in the treatment of kidney diseases, toxicity study using animal models, and the phytochemistry of the species. Materials and methodsThe chemical profile of Costus spiralis leaves extract (CSLE) was obtained for the hydroethanolic extract by ultra-performance liquid chromatography coupled to a mass spectrometer and ultraviolet detector with diode array (UPLC-UV/DAD-ESI-MS). The acute oral toxicity of the extract was predicted using the neutral red uptake cytotoxicity assay. Wistar rats were used in a model in vivo for confirmation of acute oral toxicity (2000 mg/kg p.o. for 14 days.) and determination of the effect on a cisplatin-induced nephrotoxicity model. ResultsThe analysis by UPLC-UV/DAD-ESI-MS showed that the chemical composition of the extract is mostly di-glycosylated flavones of apigenin. In the extract were identified the flavones vicenin II and schaftoside. The quantification of total flavonoids by spectrometry showed 0.880%. CSLE proved to be safe for acute oral administration (2000 mg/kg) with an IC50 value of 222.9 μg/mL and predicted oral toxic dose of 523.82 μg/mL in a neutral red uptake cytotoxicity assay. The absence of death allows the classification of the extract in class 5 according to OECD 423 guidelines and therefore it can be considered as a high acute safety product, which is highly relevant, considering the wide popular use of the species. In the cisplatin-induced nephrotoxicity model, C. spiralis extract (5, 15, and 30 mg/kg) significantly improved renal function, reversing almost completely the effects on plasma creatinine levels and creatinine clearance (p < 0.001). ConclusionsThis study demonstrates that oral administration of Costus spiralis extract leaves is safe and effective in restoring the renal function in rats in a cisplatin-induced nephrotoxicity. It is suggested that the observed activity is related to the flavonoids present. This hypothesis should be confirmed, and the participation of other secondary metabolites should be investigated in the future.

COVID-19–related Peripheral Arterial Thrombosis Treated in a Large Health Maintenance Organization

BackgroundCOVID-19 was initially identified as an acute respiratory disease, but it was quickly recognized that multiple organ systems could be affected. Venous thrombosis and pulmonary embolism have been well reported. However, there is a paucity of data on COVID-19–related arterial thrombosis. We examined the incidence, characteristics, treatment, and outcome in patients with acute COVID-19–related arterial thrombosis in a large health maintenance organization (HMO).MethodsA retrospective multicenter case review was performed from March 2020 to March 2021. Cases were identified through a questionnaire sent to vascular surgeons. Patient characteristics, imaging, treatment, and outcome were reviewed. Successful revascularization was defined as restoration of blood flow with viability of the end organ and absence of death within 30 days. Limb salvage was defined as prevention of major amputation (transtibial or transfemoral) and absence of death in 30 days.ResultsThere were 37,845 patients admitted with COVID-19 complications during this time. Among this group, 26 patients (0.07%) had COVID-19–related arterial thrombosis. The mean age was 61.7 years (range, 33–82 years) with 20 men (77%) and 6 women (23%). Ethnic minorities comprised 25 of 26 cases (96%). Peripheral arterial disease (PAD) was present in 4 of 26 (15%), active smoking in 1 of 26 (3.8%), and diabetes in 19 of 26 (73%) cases. Most patients developed acute arterial ischemia in the outpatient setting, 20 of 26 (77%). Of the outpatients, 6 of 20 (30%) had asymptomatic COVID-19 and 14 of 20 (70%) had only mild upper respiratory symptoms. Distribution of ischemia was as follows: 23 patients had at least one lower extremity ischemia, one patient had cerebral and lower extremity, one had mesenteric and lower extremity, and one had upper extremity ischemia. Revascularization was attempted in 21 patients, of which 12 of 21 (57%) were successful. Limb salvage was successful in 13 of 26 (50%) patients. The overall mortality was 31% (8/26).ConclusionsOur experience in a large HMO revealed that the incidence of COVID-19–related arterial thrombosis was low. The actual incidence is likely to be higher since our method of case collection was incomplete. The majority of arterial thrombosis occurred in the outpatient setting in patients with asymptomatic or mild/moderate COVID-19 respiratory disease. Acute ischemia was the inciting factor for hospitalization in these cases. Acute lower extremity ischemia was the most common presentation, and limb salvage rate was lower than that expected when compared to ischemia related to PAD. Arterial thrombosis associated with COVID-19 portends a significantly higher mortality. Education of primary care providers is paramount to prevent delayed diagnosis as most patients initially developed ischemia in the outpatient setting and did not have a high cardiovascular risk profile.

Two novel bioassays useful for the quick assessment of chemical effects on the behavior of mosquito larvae (Culicidae) and adult earthworms (Lumbricidae)

The behavior, i.e., observable response of an organism can serve as a useful indicator of environmental quality. In the absence of death and other sublethal effects, behavioral changes can represent early warning signs of toxic effects. In the present contribution, we present two novel bioassays useful for the quick assessment of chemical effects on the behavior of mosquito larvae (Culicidae) and adult earthworms (Lumbricidae). These bioassays could have applications in ecological risk assessment and laboratory based ecotoxicological testing. The novel assays are:•A bioassay for the assessment of chemical toxicity on the swimming, breathing and resting behavior of Culicidae larvae.•A bioassay for the assessment of chemical toxicity on the escape behavior of Lumbricidae in water.•These bioassays were carried out using the systemic insecticide imidacloprid and documented the relatively rapid onset of the neurotoxic effects of imidacloprid to experimental organisms.

Pharmacognostic and antidysentery screening of mixed ethanol leaf extract of Parkia biglobosa and Acanthus montanus (50:50)

Introduction: Parkia biglobosa belong to the family mimosaceae and Acanthus montanus belong to the family acanthaceae. The plants both have a multipurpose use as herbal medicine. Aim: This work investigate the pharmacognostic standard and anti-dysentery activity of the mixed ethanol extract of both plants on E. histolytical induced dysentery. Method: The phytochemical, chemo microscopy and proximate analysis were carried out using the standard procedures. The mixed extract of ratio 50:50 was administered to different groups of rats at different doses. Loperamide was administered as standard drug. The change in faecal consistency was observed and recorded. Result: The phytochemical analysis shows the presence of alkaloids, tannins, proteins, glycosides and carbohydrates. Chemomicroscopy of both plants showed the presence of starch, calcium oxalate, lignin, cellulose. While the extractive value analysis gave 25.0% and 32.7% for water extractive value and ethanol extractive value respectively (for Acanthus montanus) and 23.0% and 30.0% for water extractive value and ethanol extractive value respectively (for Parkiabiglobosa). The absence of death at 5000mg/kg of the extract shows that the lethal dose of the ethanol extract of the plant mixture is higher than 5000mg/kg which may be an indication of safety of the mixture. The anti-dysentery activity of the mixture of both plants with different concentration of 250mg/kg, 500mg/kg, 1000mg/kg body weight of ethanol extract showed a significant change in the faecal consistency of the rats. The effect obtained on the administration of 500mg/kg body weight of the extract mixture is more comparable to the standard (loperamide). Conclusion: The synergistic use of the extract contains the secondary metabolites glycosides, alkaloids, flavonoids, which may be responsible for their anti-dysentery synergistic activity. Mixed extracts from both leaves of P. biglobosa and A. montanus can be recommended as an anti-dysentery agent.

Variables Associated With Response to Therapy in Patients With Interstitial Pneumonia With Autoimmune Features.

Background/ObjectiveWe have limited knowledge regarding characteristics of patients with interstitial pneumonia with autoimmune features (IPAF) that are associated with response to immunosuppression. In this study, we used published IPAF criteria to characterize features associated with response to treatment.MethodsWe conducted a single-center medical records review study of 63 IPAF patients to evaluate for serological, clinical, and morphological characteristics that are associated with response to immunosuppression. Response was defined as % relative functional vital capacity decline of less than 10% and absence of death or lung transplant within the first year of continuous immunosuppressive therapy. Nonparametric measures of association and multivariate logistic regression were used to evaluate the relationship between baseline characteristics and immunosuppressive response.ResultsThere was a trend of greater progression among men, ever smokers, those negative for antisynthetase antibodies, and those with usual interstitial pneumonia radiographic pattern, but no statistically significant relationship was found between baseline serological, clinical, or morphological features and response to immunosuppression. Patients on combination therapy with mycophenolate mofetil and prednisone had less disease progression (p = 0.018) than those on regimens that did not include both of these medications.ConclusionsIn our cohort, baseline clinical assessment did not identify which patients with IPAF will respond to immunosuppressive therapy. Combination therapy with mycophenolate mofetil and prednisone was associated with lack of disease progression in our IPAF patients, including in IPAF–usual interstitial pneumonia. Further studies are needed to evaluate which IPAF patients would benefit from immunosuppressive therapy, antifibrotic therapy, or a combination of both.

A Human Right Approach of Right to Health During Pandemic

The right to live isn’t the absence of death; it’s living a life with good health and human dignity.’ Human rights are fundamentally linked to global health in the context of the COVID-19 pandemic. Human rights law guarantees everyone the right to the highest attainable standard of health and obligates governments to take steps to prevent threats to public health and to provide medical care to those who need it. The language and principles of human rights relate to the rights that support the survival and basic wellbeing of communities and individuals, including their rights to life, health and an adequate standard of living. Human rights law also recognizes that in the context of serious public health threats and public emergencies threatening the life of the Nation, restrictions on some rights can be justified when they have a legal basis, are strictly necessary, based on scientific evidence and neither arbitrary nor discriminatory in application, of limited duration, respectful of human dignity, subject to review, and proportionate to achieve the objective. The scale and severity of the COVID-19 pandemic clearly rises to the level of a public health threat that could justify restrictions on certain rights, such as those that result from the imposition of quarantine or isolation limiting freedom of movement. At the same time, careful attention to human rights such as non-discrimination and human rights principles such as transparency and respect for human dignity can foster an effective response amidst the turmoil and disruption that inevitably results in times of crisis and limit the harms that can come from the imposition of overly broad measures that do not meet the criteria.

Best timing of tranexamic acid administration for bleeding after trauma or childbirth remains to be established

Haemorrhage is worldwide the leading cause of maternal death1 and an important cause of death after trauma.2 Antifibrinolytic drugs inhibit the lysis of a fibrin clot and are, therefore, used...

Variation in Peritoneal Dialysis–Related Peritonitis Outcomes in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS)

Peritoneal dialysis (PD)-associated peritonitis is a significant PD-related complication. We describe the likelihood of cure after a peritonitis episode, exploring its association with various patient, peritonitis, and treatment characteristics. Observational prospective cohort study. 1,631 peritonitis episodes (1,190 patients, 126 facilities) in Australia, New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States. Patient characteristics (demographics, patient history, laboratory values), peritonitis characteristics (organism category, concomitant exit-site infection), dialysis center characteristics (use of icodextrin and low glucose degradation product solutions, policies regarding antibiotic self-administration), and peritonitis treatment characteristics (antibiotic used). Cure, defined as absence of death, transfer to hemodialysis (HD), PD catheter removal, relapse, or recurrent peritonitis within 50 days of a peritonitis episode. Mixed-effects logistic models. Overall, 65% of episodes resulted in a cure. Adjusted odds ratios (AOR) for cure were similar across countries (range, 54%-68%), by age, sex, dialysis vintage, and diabetes status. Compared with Gram-positive peritonitis, the odds of cure were lower for Gram-negative (AOR, 0.41 [95% CI, 0.30-0.57]), polymicrobial (AOR, 0.30 [95% CI, 0.20-0.47]), and fungal (AOR, 0.01 [95% CI, 0.00-0.07]) peritonitis. Odds of cure were higher with automated PD versus continuous ambulatory PD (AOR, 1.36 [95% CI, 1.02-1.82]), facility icodextrin use (AOR per 10% greater icodextrin use, 1.06 [95% CI, 1.01-1.12]), empirical aminoglycoside use (AOR, 3.95 [95% CI, 1.23-12.68]), and ciprofloxacin use versus ceftazidime use for Gram-negative peritonitis (AOR, 5.73 [95% CI, 1.07-30.61]). Prior peritonitis episodes (AOR, 0.85 [95% CI, 0.74-0.99]) and concomitant exit-site infection (AOR, 0.41 [95% CI, 0.26-0.64]) were associated with a lower odds of cure. Sample selection may be biased and generalizability may be limited. Residual confounding and confounding by indication limit inferences. Use of facility-level treatment variables may not capture patient-level treatments. Outcomes after peritonitis vary by patient characteristics, peritonitis characteristics, and modifiable peritonitis treatment practices. Differences in the odds of cure across infecting organisms and antibiotic regimens suggest that organism-specific treatment considerations warrant further investigation.

P171 Immune-mediated diseases (IMID) and COVID-19: results from an observational retrospective multicenter study

BackgroundThe novel coronavirus emerged in 2019 in Wuhan has caused a global pandemic of coronavirus disease (COVID-19). Immune-mediated diseases (IMID), as inflammatory arthritis or inflammatory bowel disease (IBD), have some special implications due to their pathogenesis and treatments. Some treatments employed in IMID are now being used in the treatment of severe COVID-19. There still exists controversy about IMID behavior and its complications. Our aim was to assess COVID-19 severity in IMID patients and its prognosis predictors.MethodsAn observational retrospective multicenter study was performed in two Spanish Hospitals (University Clinical Hospital in Santiago de Compostela and Gregorio Marañón Hospital). Patients were selected if they were diagnosed of an IMID (rheumatoid arthritis, psoriatic arthritis, espondyloarthritis, ulcerative colitis and Crohn’s disease) and had COVID-19 infection between February and April 2020. Demographic, clinical, analytical and treatment data were collected. Stata 15.1 was used to perform statistical analysis.Results91 patients were included. 55 suffered from a rheumatic disease and 36 suffered IBD. Univariable analysis reached age, comorbidity, female gender, flu vaccine, arthropathy, basal csDMARD, pneumonia and basal CRP as potential predictors of non-severe (absence of death, respiratory insufficiency, intensive care unit admission or sepsis) COVID-19 disease (p < 0.2). After multivariable analysis, only female gender (OR 4.60 [CI95% 1.00, 21.2] p=0.050), lower age (OR 0.94 [CI95% 0.88, 1.00] p=0.042) and lower basal levels of CRP (OR 0.87 [CI95% 0.77, 0.97] p=0.010) were predictors for non-severe disease (p < 0.005). Mean time of healing (symptoms solved in outpatient and hospital discharge in admitted) from COVID-19 was 13.8 days (SD 16.3). Univariable analysis showed arthropathy, COVID-19 symptomatic and basal GC dose as potential predictors of higher time-to-healing from COVID-19 disease (p < 0.2). After multivariable analysis, only lower GC basal dose predicts higher time-to-healing (OR -1.83 [CI95% -2.81, -0.84] p=0.001).11 patients deceased because of SARS-CoV-2 infection. Univariable analysis reached age, basal csDMARD, pneumonia and basal CRP as potential predictors of COVID-19 mortality (p < 0.2). After multivariable analysis, only higher age was a predictor for mortality (OR 1.14 [CI95% 1.04,1.25] p=0.006).ConclusionIMID patients showed similar predictors of mortality than general population involving COVID-19. Immune-modulating agents did not seem to overshadow the prognosis of COVID-19 infection. Female gender, lower age and lower basal CRP is associated with mild COVID-19 disease as well higher age points out the worst prognosis. Even that, each case should be individualized.

POS1264 IMMUNE-MEDIATED DISEASES (IMID) AND CORONAVIRUS DISEASE 2019 (COVID-19): RESULTS FROM AN OBSERVATIONAL RETROSPECTIVE MULTICENTER STUDY

Background:The novel coronavirus emerged in 2019 in Wuhan has caused a global pandemic of coronavirus disease (COVID-19). Immune-mediated diseases (IMID), as inflammatory arthritis or inflammatory bowel disease (IBD), have some special implications due to their pathogenesis and treatments. Some treatments employed in IMID are now being used in the treatment of severe COVID-19. There still exists controversy about IMID behavior and its complications.1, 2Objectives:To assess COVID-19 severity in IMID patients and its prognosis predictors.Methods:An observational retrospective multicenter study was performed in two Spanish Hospitals (Clinical University Hospital in Santiago de Compostela and Gregorio Marañón Hospital). Patients were selected if they were diagnosed of an IMID (rheumatoid arthritis, psoriatic arthritis, espondyloarthritis, ulcerative colitis and Crohn’s disease) and had COVID-19 infection between February and April 2020.Demographic, clinical, analytical and treatment data were collected. Logistic regression was used to evaluate potential predictors.Stata 15.1 was used to perform statistical analysis.Results:91 patients were recruited. 55 suffered from a rheumatic disease and 36 suffer IBD. Baseline characteristics are shown in Table 1.Univariable analysis reached age, comorbidity, female gender, flu vaccine, arthropathy, basal classical synthetic anti-rheumatic drugs (csDMARD), pneumonia and basal C-reactive protein (CRP) as potential predictors of non-severe (absence of death, respiratory insufficiency, intensive care unit admission or sepsis) COVID-19 disease (p &lt; 0.2). After multivariable analysis, only female gender (OR 4.60 [CI95% 1.00, 21.2] p=0.050), lower age (OR 0.94 [CI95% 0.88, 1.00] p=0.042) and lower basal levels of CRP (OR 0.87 [CI95% 0.77, 0.97] p=0.010) were predictors for non-severe disease (p &lt; 0.005).Mean time of healing (symptoms solved in outpatient and hospital discharge in admitted) from COVID-19 was 13.8 days (SD 16.3). Univariable analysis showed arthropathy, COVID-19 symptomatic and basal glucocorticoids (GC) dose as potential predictors of higher time-to-healing from COVID-19 disease (p &lt; 0.2). After multivariable analysis, only lower GC basal dose predicts higher time-to-healing (OR -1.83 [CI95% -2.81, -0.84] p=0.001).11 patients deceased because of COVID-19. Univariable analysis reached age, basal csDMARD, pneumonia and basal CRP as potential predictors of COVID-19 mortality (p &lt; 0.2). After multivariable analysis, only higher age was a predictor for mortality (OR 1.14 [CI95% 1.04,1.25] p=0.006).Conclusion:IMID patients showed similar predictors of mortality than general population involving COVID-19. Immune-modulating agents did not seem to overshadow the prognosis of COVID-19 infection. Female gender, lower age and lower basal CRP could select a cohort of “good” prognosis patients with mild COVID-19 disease as well higher age points out the worst prognosis. Even that, each case should be individiualized.

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections.

In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion. One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively. Each of the antibiotic regimens are safe in premature infants with cIAI. NCT0199499.

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial

Spinal muscular atrophy type 1 is a motor neuron disorder resulting in death or the need for permanent ventilation by age 2 years. We aimed to evaluate the safety and efficacy of onasemnogene abeparvovec (previously known as AVXS-101), a gene therapy delivering the survival motor neuron gene (SMN), in symptomatic patients (identified through clinical examination) with infantile-onset spinal muscular atrophy. STR1VE was an open-label, single-arm, single-dose, phase 3 trial done at 12 hospitals and universities in the USA. Eligible patients had to be younger than 6 months and have spinal muscular atrophy with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes per kg) for 30-60 min. During the outpatient follow-up, patients were assessed once per week, beginning at day 7 post-infusion for 4 weeks and then once per month until the end of the study (age 18 months or early termination). Coprimary efficacy outcomes were independent sitting for 30 s or longer (Bayley-III item 26) at the 18 month of age study visit and survival (absence of death or permanent ventilation) at age 14 months. Safety was assessed through evaluation of adverse events, concomitant medication usage, physical examinations, vital sign assessments, cardiac assessments, and laboratory evaluation. Primary efficacy endpoints for the intention-to-treat population were compared with untreated infants aged 6 months or younger (n=23) with spinal muscular atrophy type 1 (biallelic deletion of SMN1 and two copies of SMN2) from the Pediatric Neuromuscular Clinical Research (PNCR) dataset. This trial is registered with ClinicalTrials.gov, NCT03306277 (completed). From Oct 24, 2017, to Nov 12, 2019, 22 patients with spinal muscular atrophy type 1 were eligible and received onasemnogene abeparvovec. 13 (59%, 97·5% CI 36-100) of 22 patients achieved functional independent sitting for 30 s or longer at the 18 month of age study visit (vs 0 of 23 patients in the untreated PNCR cohort; p<0·0001). 20 patients (91%, 79-100]) survived free from permanent ventilation at age 14 months (vs 6 [26%], 8-44; p<0·0001 in the untreated PNCR cohort). All patients who received onasemnogene abeparvovec had at least one adverse event (most common was pyrexia). The most frequently reported serious adverse events were bronchiolitis, pneumonia, respiratory distress, and respiratory syncytial virus bronchiolitis. Three serious adverse events were related or possibly related to the treatment (two patients had elevated hepatic aminotransferases, and one had hydrocephalus). Results from this multicentre trial build on findings from the phase 1 START study by showing safety and efficacy of commercial grade onasemnogene abeparvovec. Onasemnogene abeparvovec showed statistical superiority and clinically meaningful responses when compared with observations from the PNCR natural history cohort. The favourable benefit-risk profile shown in this study supports the use of onasemnogene abeparvovec for treatment of symptomatic patients with genetic or clinical characteristics predictive of infantile-onset spinal muscular atrophy type 1. Novartis Gene Therapies.