Unhealthy alcohol and drug use is associated with an increased length of stay and hospital cost in patients undergoing major upper gastrointestinal and pancreatic oncologic resections

BackgroundFew studies evaluate the impact of unhealthy alcohol and drug use on the risk and severity of postoperative outcomes after upper gastrointestinal and pancreatic oncologic resections.MethodsThe National Inpatient Sample was queried to identify patients undergoing total gastrectomy, esophagectomy, total pancreatectomy, and pancreaticoduodenectomy between 2012 and 2015. Unhealthy alcohol and drug use was assessed by the International Classification of Diseases, Ninth Revision, and National Inpatient Sample coder designation. Multivariable regression was used to identify associations between alcohol and drug use and postoperative complication, duration of stay, hospital cost, and mortality.ResultsIn the study, 59,490 patients met inclusion criteria; 2,060 (3.5%) had unhealthy alcohol use; 1,265 (2.1%) had unhealthy drug use. Postoperative complication rates were higher in patients with alcohol and drug use than in abstainers (67.5% vs 62.8% vs 57.2%; P < .01). On multivariable regression, alcohol use was independently associated with increased risk of a nonwithdrawal complication (odds ratio 1.33 [1.05, 1.68]), and alcohol and drug use were independently associated with increased length of stay (1.54 [0.12, 2.96]) and 2.22 [0.90, 3.55] days) and cost ($5,471 [$60, $10,881] and $4,022 [$402, $7,643]), but not mortality.ConclusionUnhealthy substance use is associated with increased rates of postoperative complications, prolonged length of stay, and costs in patients undergoing major upper gastrointestinal and pancreatic oncologic resections. Screening and abstinence interventions should be incorporated into the preoperative care pathways for these patients.     

Uveitis occurrence in early inflammatory back pain. Five years data from the prospective French nationwide DESIR cohort

ObjectiveUveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors.MethodsDESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. Significance: P less than 0.05.ResultsAfter 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI: 15.4–22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84–1.74]/100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI.ConclusionFive-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.     

Optimal donation of kidney transplants after controlled circulatory death

Controlled donation after circulatory death (cDCD) is used for “extended criteria” donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12–1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20–2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31–2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.     

Renal functional reserve in children with reduced renal mass: study by two dietary periods

It has been suggested that the renal functional reserve (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (C _in) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dictary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3–4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%–139%) RDA for the LP period and 220% (163%–319%) RDA for the HP period.C _in did not change in 14 children with GFR below (n=7) or within (n=7) the normal range.C _in was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m². Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.     

Spiral twist of the spermatic cord: a reliable sign of testicular torsion

Background. Colour Doppler sonography (CDS) has become the procedure of choice in evaluating testicular perfusion but false negative findings have been reported. Objective. To determine if direct visualisation of the twisted spermatic cord using high resolution US is a reliable sign to assess testicular torsion. Material and methods. Thirty patients (aged 2–26 years) with equivocal diagnosis of testicular torsion prospectively underwent high resolution and CDS. The results were correlated with surgical findings. Serial transverse and longitudinal scans were performed to compare the scrotal contents on each side and study the complete spermatic cord course, from inguinal canal to testis, to detect a spiral twist. Results. In 14 of the 23 cases of torsion, the diagnosis was based on the colour Doppler findings in the scrotum because blood flow was absent in the symptomatic testis and detectable without difficulty on the normal side. In nine cases, CDS was unreliable; in six cases intratesticular perfusion was present in a twisted testis and in three small boys, no colour signal was obtained in either testis. In all cases of torsion, the spiral twist of spermatic cord was detected at the external inguinal ring. The twist induced an abrupt change in spermatic cord course, size and shape below the point of torsion. It appeared in the scrotum as a round or oval, homogeneous or heterogeneous extratesticular mass with or without blood flow, that could be connected cephalad with the normal inguinal cord. In the other seven cases (three late torsions of the appendix testis, one epididymo-orchitis and three torsions with spontaneous reduction), no spiral twist was detectable. Conclusion. The detection of spermatic cord spiral twist appears a reliable US sign of torsion whatever the testicular consequences. Received: 1 December 1997 Accepted: 17 June 1998     

Nosocomial infection and multidrug-resistant bacteria surveillance in intensive care units: a survey in France.

OBJECTIVES: To evaluate nosocomial infection (NI) surveillance strategies in French ICUs and to identify similar patterns defining subsets within which comparisons can be made. DESIGN: A questionnaire was sent to all French ICUs, and a random sample of nonresponders was interviewed. PARTICIPANTS: Three hundred ninety-five responder ICUs (69%) in France. RESULTS: In 282 ICUs (71%), a dedicated ICU staff member was responsible for infection control activities. The microbiology laboratory was usually in the hospital (90%) and computerized (94%) but issued regular hospital microbiology records in only 48% of cases. Patients receiving mechanical ventilation, central venous catheterization, and urinary catheterization were 90%, 79%, and 60%, respectively. Patients were screened for carriage of multidrug-resistant bacteria on admission and during the stay in 70% and 60% of ICUs, respectively, most often targeting MRSA. Quantitative cultures were used to diagnose ventilator-associated pneumonia (VAP) in 90% of ICUs, including distal specimens in 80% and bronchoscopy specimens in 60%. Quantitative central venous catheter (CVC)-segment cultures were used in 70% of ICUs. All CVCs were cultured routinely in 53% of the ICUs. Despite wide variations in infection control and surveillance strategies, multiple correspondence analysis identified 13 key points (4 structural variables and 9 variables concerning the diagnosis of VAP, the surveillance and diagnosis of catheter-related and urinary tract infections, and the mode of screening of MRSA carriers) that categorize the variability of French ICUs' approaches to NIs. CONCLUSION: This study revealed profound differences in NI surveillance strategies across ICUs, indicating a need for caution when using NI surveillance data for comparisons and benchmarking.     

When Fever, Paracetamol? Theory and Practice in a Paediatric Outpatient Clinic

Objective: To determine how medical and nursing staff treat feverish children and compare the findings with their theoretical knowledge, evaluating how they might contribute to fever phobia in parents.Setting: Paediatric Emergency Department.Method: In the first step, we analysed prospectively the files of all children having consulted the Paediatric Emergency Department with a history of fever or of body temperature above 38 °C during a 2-week period. The second step consisted of evaluating knowledge and perception of fever of doctors and nurses using a questionnaire.Main outcome measures: Prospective study: final diagnosis (viral, non- invasive bacterial disorders, invasive bacterial disorders), site of measurement and average temperature. Evaluation of theoretical knowledge: definition of fever, site of measurement, evaluation of the child’s clinical state, antipyretic drug choice.Results: A total of 114 children under 5 years of age were enrolled and 24 caregivers (12 doctors, 12 nurses, 90 of the staff) responded to the questionnaire. The results showed good consistency in theoretical knowledge, but an excessive fear about cerebral damage was also shown by doctors. This belief likely contributes to the transmission of fever phobia to parents. In contrast, analysis of children management showed that fever was often under-treated, especially by nurses and even more so by parents. Paracetamol remained the first-line antipyretic drug yet was often administered in insufficient doses. Non-steroidal anti-inflammatory drugs were seldom used, except by parents (16 of all the children). Contrary to literature, the favourite route of administration was the rectal one. Physical methods like sponging were largely used by nurses, despite the uncertainties in their real effectiveness and their known side-effects.Conclusion: Our study showed that the management of feverish children was globally correct in the Paediatric Emergency Department, but several improvement measures have been taken (e.g. tables of normal and abnormal ranges of temperature, recommended temperature measurement techniques, dosage regimen of antipyretic drugs, guidelines to parents), justifying the implementation of a pharmaceutical follow-up.     

Managing the Impact of Immunogenicity in an Era of Immunotherapy: From Bench to Bedside

Biotherapeutics have revolutionized our ability to treat life-threatening diseases. Despite clinical success, the use of biotherapeutics has sometimes been limited by the immune response mounted against them in the form of anti-drug antibodies (ADAs). The multifactorial nature of immunogenicity has prevented a standardized approach for assessing this and each of the assessment methods developed so far does not exhibit high enough reliability to be used alone, due to limited predictiveness. This prompted the Roche Pharma Research and Early Development (pRED) Immunogenicity Working Group to establish an internal preclinical immunogenicity toolbox of in vitro/in vivo approaches and accompanying guidelines for a harmonized assessment and management of immunogenicity in early development. In this article, the complex factors influencing immunogenicity and their associated clinical ramifications are discussed to highlight the importance of an end-to-end approach conducted from lead optimization to clinical candidate selection. We then examine the impact of the resulting lead candidate categorization on the design and implementation of a multi-tiered ADA/immunogenicity assay strategy prior to phase I (entry into human) through early clinical development. Ultimately, the Immunogenicity Toolbox ensures that Roche pRED teams are equipped to address immunogenicity in a standardized manner, paving the way for lifesaving products with improved safety and efficacy.