Medical publishing: a flawed model in dire need of reform

Recently, in the midst of the Covid-19 pandemic, high-profile retractions of some papers published in prestigious medical journals have highlighted the necessity for structural reform to the current model of medical publishing. We discuss what ails the current system and what can be done to remedy it. (AU)

Patient experiences of left-sided colorectal resection by robotic, conventional laparoscopic and open approaches: a qualitative study.

BACKGROUND: Robotic surgery (RS) is increasingly employed in colorectal surgical practice, widening the range of surgical techniques offered to patients. We investigated the perceptions of patients with colorectal cancer in relation to RS, open surgery (OS) and conventional laparoscopic surgery (CLS), to identify ideas or assumptions which, in the context of shared surgeon-patient decision-making, may affect the resultant choice of surgical technique. We also investigated salient factors affecting patients' perioperative experience, including those of RS patients, to guide improvements in care and preoperative patient preparation. METHODS: This study was conducted on patients who underwent resection of left-sided colorectal cancer at a large UK teaching hospital from November 2020 to July 2021. Purposive sampling was used to ensure a roughly equal proportion of patients who underwent RS, CLS and OS. The patients included in the study participated in semi-structured interviews six weeks postoperatively. The interview schedule allowed discussion around patients' experience of their surgery and postoperative recovery, and their perceptions of surgical techniques. Interview transcripts were coded manually using inductive thematic analysis, and analyst triangulation was employed to refine coding schemes and ensure reliability of emerging themes. RESULTS: Twenty-seven patients were recruited to the study; RS n = 9 (median age 69 [range 60-80] years); CLS n = 10 (median age 72 [range 32-82] years; OS n = 8 (median age 71 [range 60-75] years). Patients understood the technological benefits of RS but were concerned by a risk of technological failure causing patient harm. OS was understood to be associated with more pain and longer recovery than RS or CLS. Patients perceived CLS to be more technically challenging compared with OS. Less pain and smaller wounds than expected were significant positive factors in the experience of RS and CLS patients specifically. Complications and emotional impact were significant factors in the experience of all groups, for which many patients felt underprepared. CONCLUSIONS: Patients generally have a positive view of RS and technical innovation in surgery. Concerns mostly centred around failure of technology. Many patients felt unprepared for significant factors in their perioperative experience. Surgeons and healthcare providers should be prepared to address patients' perceptions and expectations of colorectal surgery preoperatively.

Medical publishing: a flawed model in dire need of reform.

Recently, in the midst of the Covid-19 pandemic, high-profile retractions of some papers published in prestigious medical journals have highlighted the necessity for structural reform to the current model of medical publishing. We discuss what ails the current system and what can be done to remedy it.

Association between cumulative surgeon experience and long-term outcomes in complex abdominal wall reconstruction.

PURPOSE: While many factors have been correlated with lesser outcomes in abdominal wall reconstruction (AWR), the impact of surgeon experience has yet to be elucidated. We sought to evaluate the effect of cumulative surgeon experience on long-term complex AWR outcomes. METHODS: We conducted a comprehensive review of all consecutive patients who underwent AWR using biologic mesh for the repair of ventral hernias or tumor resection defects from March 2005 to June 2019. The primary outcome measure was hernia recurrence (HR). Secondary outcomes were surgical site occurrences (SSOs) and surgical site infections (SSIs). Patients were a priori categorized into the following groups according to the cumulative number of hernia repairs performed by their surgeons: low (< 50), moderate experience (50-100), and high (> 100) experience. RESULTS: We identified 60 surgeons and 650 consecutive patients (62% women) who met our inclusion criteria. In adjusted models, AWR performed by surgeons with high experience was associated with a fourfold lower risk of HR (hazard ratio, 0.28; 95% confidence interval, 0.08 to 0.87), but the odds of surgical site occurrences (odds ratio, 0.72, 95% confidence interval, 0.34 to 1.52) and surgical site infections (odds ratio, 0.89, 95% confidence interval, 0.26 to 2.86) did not differ significantly in the high-experience group. CONCLUSIONS: High surgical experience, defined as > 100 cumulative hernia repairs, is predictive for markedly lower HR rates in complex AWR. These findings have potential implications for preoperative risk assessment, patient-centered surgeon selection, regulatory oversight, specific referral patterns, designations of centers of excellence, and individual provider or trainee quality improvement.

Chemical and Cellular Formation of Reactive Oxygen Species from Secondary Organic Aerosols in Epithelial Lining Fluid.

INTRODUCTION: Oxidative stress mediated by reactive oxygen species (ROS) is a key process for adverse aerosol health effects. Secondary organic aerosols (SOA) account for a major fraction of particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5). PM2.5 inhalation and deposition into the respiratory tract causes the formation of ROS by chemical reactions and phagocytosis of macrophages in the epithelial lining fluid (ELF), but their relative contributions are not well quantified and their link to oxidative stress remains uncertain. The specific aims of this project were (1) elucidating the chemical mechanism and quantifying the formation kinetics of ROS in the ELF by SOA; (2) quantifying the relative importance of ROS formation by chemical reactions and macrophages in the ELF. METHODS: SOA particles were generated using reaction chambers from oxidation of various precursors including isoprene, terpenes, and aromatic compounds with or without nitrogen oxides (NOx). We collected size-segregated PM at two highway sites in Anaheim, CA, and Long Beach, CA, and at an urban site in Irvine, CA, during two wildfire events. The collected particles were extracted into water or surrogate ELF that contained lung antioxidants. ROS generation was quantified using electron paramagnetic resonance (EPR) spectroscopy with a spin-trapping technique. PM oxidative potential (OP) was also quantified using the dithiothreitol assay. In addition, kinetic modeling was applied for analysis and interpretation of experimental data. Finally, we quantified cellular superoxide release by RAW264.7 macrophage cells upon exposure to quinones and isoprene SOA using a chemiluminescence assay as calibrated with an EPR spin-probing technique. We also applied cellular imaging techniques to study the cellular mechanism of superoxide release and oxidative damage on cell membranes. RESULTS: Superoxide radicals (·O2-) were formed from aqueous reactions of biogenic SOA generated by hydroxy radical (·OH) photooxidation of isoprene, ß-pinene, α-terpineol, and d-limonene. The temporal evolution of ·OH and ·O2- formation was elucidated by kinetic modeling with a cascade of aqueous reactions, including the decomposition of organic hydroperoxides (ROOH), ·OH oxidation of primary or secondary alcohols, and unimolecular decomposition of α-hydroxyperoxyl radicals. Relative yields of various types of ROS reflected the relative abundance of ROOH and alcohols contained in SOA, which generated under high NOx conditions, exhibited lower ROS yields. ROS formation by SOA was also affected by pH. Isoprene SOA had higher ·OH and organic radical yields at neutral than at acidic pH. At low pH ·O2- was the dominant species generated by all types of SOA. At neutral pH, α-terpineol SOA exhibited a substantial yield of carbon-centered organic radicals (R·), while no radical formation was observed by aromatic SOA.Organic radicals in the ELF were formed by mixtures of Fe2+ and SOA generated from photooxidation of isoprene, α-terpineol, and toluene. The molar yields of organic radicals by SOA were 5-10 times higher in ELF than in water. Fe2+ enhanced organic radical yields by a factor of 20-80. Ascorbate mediated redox cycling of iron ions and sustained organic peroxide decomposition, as supported by kinetic modeling reproducing time- and concentration-dependence of organic radical formation, as well as by additional experiments observing the formation of Fe2+ and ascorbate radicals in mixtures of ascorbate and Fe3+. ·OH and superoxide were found to be efficiently scavenged by antioxidants.Wildfire PM mainly generated ·OH and R· with minor contributions from superoxide and oxygen-centered organic radicals (RO·). PM OP was high in wildfire PM, exhibiting very weak correlation with radical forms of ROS. These results were in stark contrast with PM collected at highway and urban sites, which generated much higher amounts of radicals dominated by ·OH radicals that correlated well with OP. By combining field measurements of size-segregated chemical composition, a human respiratory tract model, and kinetic modeling, we quantified production rates and concentrations of different types of ROS in different regions of the ELF by considering particle-size-dependent respiratory deposition. While hydrogen peroxide (H2O2) and ·O2- production were governed by Fe and Cu ions, ·OH radicals were mainly generated by organic compounds and Fenton-like reactions of metal ions. We obtained mixed results for correlations between PM OP and ROS formation, providing rationale and limitations of the use of oxidative potential as an indicator for PM toxicity in epidemiological and toxicological studies.Quinones and isoprene SOA activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in macrophages, releasing massive amounts of superoxide via respiratory burst and overwhelming the superoxide formation by aqueous chemical reactions in the ELF. The threshold dose for macrophage activation was much smaller for quinones compared with isoprene SOA. The released ROS caused lipid peroxidation to increase cell membrane fluidity, inducing oxidative damage and stress. Further increases of doses led to the activation of antioxidant response elements, reducing the net cellular superoxide production. At very high doses and long exposure times, chemical production became comparably important or dominant if the escalation of oxidative stress led to cell death. CONCLUSIONS: The mechanistic understandings and quantitative information on ROS generation by SOA particles provided a basis for further elucidation of adverse aerosol health effects and oxidative stress by PM2.5. For a comprehensive assessment of PM toxicity and health effects via oxidative stress, it is important to consider both chemical reactions and cellular processes for the formation of ROS in the ELF. Chemical composition of PM strongly influences ROS formation; further investigations are required to study ROS formation from various PM sources. Such research will provide critical information to environmental agencies and policymakers for the development of air quality policy and regulation.

Association of CRP Haplotypes in Rheumatoid Arthritis and their Correlation with Severity of the Disease.

BACKGROUND: Rheumatoid arthritis is a heterogenous autoimmune disorder of unknown cause with variable clinical expression. Genetic factors play an important role and likely account for about 60% of disease susceptibility and expression. The aim of this study to find out the association of CRP haplotypes in rheumatoid arthritis and their correlation with severity of the disease. MATERIAL AND METHODS: This was case control study where in all available patients and volunteers (only for blood samples) were recruited. Peripheral blood samples of patients were collected at Rheumatology Clinic and Medicine Department of S.P. Medical College, Bikaner in collaboration with Department of Biological Sciences, BITS, Pilani-Hyderabad during July 2009 to January 2012. 100 control subjects with no known history of disease and 135 cases were recruited as per pre-decided inclusion and exclusion criteria. A tag SNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. RESULTS: Cases comprised of 98 females (Mean age 43.01+13.23 yrs) and 37 (mean age 47.4+14.9 years) males. The Control group comprised of 100 unrelated healthy controls. The cases and controls did not differ significantly for any of the clinical parameters, except for serum CRP levels. The allele distribution of rs1205 polymorphism among the studied cases and controls, which was statistical non-significant. The rs3093066 polymorphism located at the 3` position of the gene in the UTR at position number 157949723. The rs3116640 polymorphism located at 157948938 position on chromosome1 and the allele distribution of rs3116637 polymorphism among cases and controls which was also found to be monomorphic respectively. CONCLUSION: Extending the studies to a larger cohort will also allow genetic analyses of clinically defined endophenotypes observed in the patients of this chronic metabolic disease with attributes of autoimmune disorder and multiple symptoms in patients. Genetic studies can also impact strategies adopted for effective personalized treatment for this progressively debilitating disease.

Partnering for rotavirus vaccine introduction in India: A retrospective analysis.

BACKGROUND: The pre-existing partner network created in India for the delivery of polio vaccines was initially used to eradicate polio and later on embedded in the health systems network to promote routine immunization and other health interventions efficiently. The experience from this network offered lessons for strengthening the health care systems and provided a well-established network that could be utilized for other vaccine initiatives. It has also been established that successful partnerships between a broad range of stakeholders provide support, strengthen the health system, and accelerate vaccine innovation, introduction, access, logistics, and communication support. However, beyond polio eradication, there have not been too many documented success stories of vaccine introduction, which could be replicated in other new vaccine introductions and allied health initiatives. The authors have reviewed the successful and time-bound introduction of rotavirus vaccine (RVV) in India in the present article. METHODS: The review was conducted based on a partnership framework which analysed multiple factors-partnership prerequisites, partnership model, partnership process, and partnership performance, thereby providing a comprehensive insight into the successful utilization of partnership networks for rotavirus vaccine introduction under the Universal Immunization Program in India. RESULTS & CONCLUSION: The review also highlights the role of a lead agency in creating a fertile ground for lush, efficient, and effective partnerships amongst different stakeholders. The already existing RVV partnership framework reviewed by the authors can be successfully utilized for future new vaccine introductions.

Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study.

PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Renal impairment after ileostomy formation: a frequent event with long-term consequences.

AIM: High stoma output and dehydration is common following ileostomy formation. However, the impact of this on renal function, both in the short term and after ileostomy reversal, remains poorly defined. We aimed to assess the independent impact on kidney function of an ileostomy after rectal cancer surgery and subsequent reversibility after ileostomy closure. METHODS: This retrospective single-site cohort study identified patients undergoing rectal cancer resection from 2003 to 2017, with or without a diverting ileostomy. Renal function was calculated preoperatively, before ileostomy closure, and 6 months after ileostomy reversal (or matched times for patients without ileostomy). Demographics, oncological treatments and nephrotoxic drug prescriptions were assessed. Outcome measures were deterioration from baseline renal function and development of moderate/severe chronic kidney disease (CKD ≥ 3). Multivariate analysis was performed to assess independent risk factors for postoperative renal impairment. RESULTS: Five hundred and eighty-three of 1213 patients had an ileostomy. Postoperative renal impairment occurred more frequently in ileostomates (9.5% absolute increase in rate of CKD ≥ 3; P < 0.0001) vs no change in patients without an ileostomy (P = 0.757). Multivariate analysis identified ileostomy formation, age, anastomotic leak and renin-angiotensin system inhibitors as independently associated with postoperative renal decline. Despite stoma closure, ileostomates remained at increased risk of progression to new or worse CKD [74/438 (16.9%)] compared to patients without an ileostomy [36/437 (8.2%), P = 0.0001, OR 2.264 (1.49-3.46)]. CONCLUSIONS: Ileostomy formation is independently associated with kidney injury, with an increased risk persisting after stoma closure. Strategies to protect against kidney injury may be important in higher risk patients (elderly, receiving renin-angiotensin system antihypertensives, or following anastomotic leakage).

Correction: Regulation of dopaminergic function: An [18F]-DOPA PET apomorphine challenge study in humans.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Does intra-operative flexible endoscopy reduce anastomotic complications following left-sided colonic resections? A systematic review and meta-analysis.

AIM: Postoperative anastomotic leakage (AL) or bleeding (AB) significantly impacts on patient outcome following colorectal resection. To minimize such complications, surgeons can utilize different techniques perioperatively to assess anastomotic integrity. We aim to assess published anastomotic complication rates following left-sided colonic resection, comparing the use of intra-operative flexible endoscopy (FE) against conventional tests used to assess anastomotic integrity. METHODS: PubMed/MEDLINE and Embase online databases were searched for non-randomized and randomized case-control studies that investigated postoperative AL and/or AB rates in left-sided colonic resections, comparing intra-operative FE against conventional tests. Data from eligible studies were pooled, and a meta-analysis using Review Manager 5.3 software was performed to assess for differences in AL and AB rates. RESULTS: Data from six studies were analysed to assess the impact of FE on postoperative AL and AB rates (1084 and 751 patients respectively). Use of FE was associated with reduced postoperative AL and AB rates, from 6.9% to 3.5% and 5.8% to 2.4% respectively. Odds ratios favoured intra-operative FE: 0.37 (95% CI 0.21-0.68, P = 0.001) for AL and 0.35 (95% CI 0.15-0.82, P = 0.02) for AB. CONCLUSION: This meta-analysis showed that the use of intra-operative FE is associated with a reduced rate of postoperative AL and AB, compared to conventional anastomotic testing methods.

Correction: Altered activation and connectivity in a hippocampal-basal ganglia-midbrain circuit during salience processing in subjects at ultra high risk for psychosis.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.

Correction: Regulation of dopaminergic function: an [18F]-DOPA PET apomorphine challenge study in humans.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.

Genetic profile and mutation spectrum of Leber congenital amaurosis in a larger Indian cohort using high throughput targeted re-sequencing.

To provide a comprehensive data on the prevalence of mutations in Leber congenital amaurosis (LCA) candidate genes from a larger Indian cohort. Ninety-two unrelated subjects were recruited after complete ophthalmic examination and informed consent. Targeted re-sequencing of 20 candidate genes was performed using Agilent HaloPlex target enrichment assay and sequenced on Illumina MiSeq platform. The data were analyzed using standard bioinformatics pipeline, variants annotated, validated and segregated. Genotype-phenotype correlation was performed for the mutation-positive cases. Targeted next generation sequencing (NGS) for the 20 candidate genes generated data with an average sequence coverage and depth of 99.03% and 134X, respectively. Mutations were identified in 61% (56/92) of the cases, which were validated, segregated in the families and absent in 200 control chromosomes. These mutations were observed in 14/20 candidate genes and 39% (21/53) were novel. Distinct phenotypes were observed with respect to genotypes. To our knowledge, this study presents the first comprehensive mutation spectrum of LCA in a large Indian cohort. The mutation-negative cases indicate scope for finding novel candidate gene(s) although mutations in deep intronic and regulatory regions cannot be ruled out.

Altered activation and connectivity in a hippocampal-basal ganglia-midbrain circuit during salience processing in subjects at ultra high risk for psychosis.

Animal models of psychosis propose that abnormal hippocampal activity drives increased subcortical dopamine function, which is thought to contribute to aberrant salience processing and psychotic symptoms. These effects appear to be mediated through connections between the hippocampus, ventral striatum/pallidum and the midbrain. The aim of the present study was to examine the activity and connectivity in this pathway in people at ultra high risk (UHR) for psychosis. Functional magnetic resonance imaging was used to compare neural responses in a hippocampal-basal ganglia-midbrain network during reward, novelty and aversion processing between 29 UHR subjects and 32 healthy controls. We then investigated whether effective connectivity within this network is perturbed in UHR subjects, using dynamic causal modelling (DCM). Finally, we examined the relationship between alterations in activation and connectivity in the UHR subjects and the severity of their psychotic symptoms. During reward anticipation, UHR subjects showed greater activation than controls in the ventral pallidum bilaterally. There were no differences in activation during novelty or aversion processing. DCM revealed that reward-induced modulation of connectivity from the ventral striatum/pallidum to the midbrain was greater in UHR subjects than controls, and that in UHR subjects, the strength of connectivity in this pathway was correlated with the severity of their abnormal beliefs. In conclusion, ventral striatal/pallidal function is altered in people at UHR for psychosis and this is related to the level of their psychotic symptoms.

Optimizing the Bioavailability of Subcutaneously Administered Biotherapeutics Through Mechanochemical Drivers.

The subcutaneous route offers myriad benefits for the administration of biotherapeutics in both acute and chronic diseases, including convenience, cost effectiveness and the potential for automation through closed-loop systems. Recent advances in parenteral administration devices and the use of additives which enhance drug dispersion have generated substantial additional interest in IV to SQ switching studies. Designing pre-clinical and clinical studies using SQ mediated delivery however requires deep understanding of complex inter-related physiologies and transport pathways governing the interstitial matrix, vascular system and lymphatic channels. This expert review will highlight key structural features which contribute to transport and biodistribution in the subcutaneous space and also assess the impact of drug formulations. Based on the rapidly growing interest in the SQ delivery route, a number of potential areas for future development are highlighted, which are likely to allow continued evolution and innovation in this important area.

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

BACKGROUND: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. METHODS: A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. RESULTS: In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. CONCLUSIONS: As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.