The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

Mandatory reporting legislation in Canada: improving systems for patient safety?

Patient safety is a complex systems issue. In this study, we used a scoping review of peer-reviewed literature and a case study of provincial and territorial legislation in Canada to explore the influence of mandatory reporting legislation on patient safety outcomes in hospital settings. We drew from a conceptual model that examines the components of mandatory reporting legislation that must be in place as a part of a systems governance approach to patient safety and used this model to frame our results. Our results suggest that mandatory reporting legislation across Canada is generally designed to gather information about - rather than respond to and prevent - patient safety incidents. Overall, we found limited evidence of impact of mandatory reporting legislation on patient safety outcomes. Although legislation is one lever among many to improve patient safety outcomes, there are nonetheless several considerations for patient safety legislation to assist in broader system improvement efforts in Canada and elsewhere. Legislative frameworks may be enhanced by strengthening learning systems, accountability mechanisms and patient safety culture.

"I Like and Prefer to Work Alone": Social Anxiety, Academic Self-Efficacy, and Students' Perceptions of Active Learning.

Although active learning improves student outcomes in science, technology, engineering, and mathematics (STEM) programs, it may provoke anxiety in some students. We examined whether two psychological variables, social anxiety (psychological distress relating to the fear of negative evaluation by others) and academic self-efficacy (confidence in one's ability to overcome academic challenges), interact with student perceptions of evidence-based instructional practices (EBIPs) and associate with their final grades in a STEM-related course. Human anatomy and physiology students in community college courses rated various EBIPs for their perceived educational value and their capacity to elicit anxiety (N = 227). In general, practices causing students the most anxiety (e.g., cold calling) were reported by students as having the least educational value. When controlling for students' self-reported grade point averages, socially anxious students rated several EBIPs as more anxiety inducing, whereas high-efficacy students reported less anxiety surrounding other EBIPs. Furthermore, mediation analysis revealed that individual differences in academic self-efficacy at the beginning of the term explained some of the negative association between students' social anxiety levels and final grades in the course. Our results, obtained in a community college context, support a growing body of evidence that social anxiety and academic self-efficacy are linked with how students perceive and perform in an active-learning environment.

Balloon Eustachian tuboplasty treatment of longstanding Eustachian tube dysfunction.

BACKGROUND: Eustachian tube dysfunction is a poorly defined condition associated with various symptoms and it can predispose to middle-ear disease. Balloon dilation Eustachian tuboplasty has been proposed as a treatment for Eustachian tube dysfunction. OBJECTIVE: To evaluate the subjective and objective outcomes of balloon dilation Eustachian tuboplasty in patients with recurrent, previously treated chronic Eustachian tube dysfunction. METHODS: The study was conducted on 11 patients (13 ears) who had undergone previous unsuccessful medical and surgical treatment. Tympanometry was the primary outcome measure. Secondary outcome measures included pure tone audiogram assessment and seven-item Eustachian Tube Dysfunction Questionnaire score. RESULTS: Balloon dilation Eustachian tuboplasty resulted in significant improvements in 11 patients' subjective but not objective outcome measures. CONCLUSION: The objective abnormality and subjective symptoms in Eustachian tube dysfunction may represent two distinct pathological processes, which may nevertheless influence and exacerbate each other.

Automated PCR setup for forensic casework samples using the Normalization Wizard and PCR Setup robotic methods.

Human genome, pharmaceutical and research laboratories have long enjoyed the application of robotics to performing repetitive laboratory tasks. However, the utilization of robotics in forensic laboratories for processing casework samples is relatively new and poses particular challenges. Since the quantity and quality (a mixture versus a single source sample, the level of degradation, the presence of PCR inhibitors) of the DNA contained within a casework sample is unknown, particular attention must be paid to procedural susceptibility to contamination, as well as DNA yield, especially as it pertains to samples with little biological material. The Virginia Department of Forensic Science (VDFS) has successfully automated forensic casework DNA extraction utilizing the DNA IQ(trade mark) System in conjunction with the Biomek 2000 Automation Workstation. Human DNA quantitation is also performed in a near complete automated fashion utilizing the AluQuant Human DNA Quantitation System and the Biomek 2000 Automation Workstation. Recently, the PCR setup for casework samples has been automated, employing the Biomek 2000 Automation Workstation and Normalization Wizard, Genetic Identity version, which utilizes the quantitation data, imported into the software, to create a customized automated method for DNA dilution, unique to that plate of DNA samples. The PCR Setup software method, used in conjunction with the Normalization Wizard method and written for the Biomek 2000, functions to mix the diluted DNA samples, transfer the PCR master mix, and transfer the diluted DNA samples to PCR amplification tubes. Once the process is complete, the DNA extracts, still on the deck of the robot in PCR amplification strip tubes, are transferred to pre-labeled 1.5 mL tubes for long-term storage using an automated method. The automation of these steps in the process of forensic DNA casework analysis has been accomplished by performing extensive optimization, validation and testing of the software methods.

Pregnancy-associated plasma protein-E (PAPP-E).

A full-length cDNA encoding a novel human protein was cloned from placenta cDNA. The corresponding 1542 amino acid protein sequence was termed 'pregnancy-associated plasma protein-E' (PAPP-E) as it shows a 62% homology to the human pregnancy-associated plasma protein-A (PAPP-A) that is a diagnostic marker for trisomies, especially Down syndrome. The conserved domain structure contains five motifs related to the short consensus repeats of complement proteins and selectins, three motifs related to the lin-notch motifs of proteins regulating early tissue differentiation, and a putative zinc-binding motif and active site of the metzincin-superfamily of metalloproteases. The PAPP-E gene was localized to chromosome 1q23-25. Northern blot analysis showed that PAPP-E is predominantly expressed in placenta.

MMP-TIMP interaction depends on residue 2 in TIMP-4.

Extracellular matrix remodeling and degradation are of great importance in both physiological and pathological situations. Matrix metalloproteinases (MMPs) and their natural occurring inhibitors - tissue inhibitors of metalloproteinases (TIMPs) - are involved in matrix turnover. Among the TIMPs there is only little specificity for inhibiting individual MMPs. In this report we describe the mutational analysis of the interaction of human TIMP-4 with several MMPs. The effects of different substitutions of residue 2 (Ser(2)) in the inhibitory domain of TIMP-4 were determined by kinetic measurements. Size, charge and polarity of residue 2 in the TIMP structure are key factors in MMP inhibition.

Assessing the progression of joint damage in rheumatoid arthritis.

Joint damage in rheumatoid arthritis can be assessed by plain radiographs of the hands and wrists. There are a number of established methods that give reproducible scores which relate to increasing joint damage by measuring erosions and loss of joint space. Only 3 placebo-controlled trials have shown convincing evidence that gold or cyclophosphamide reduce the rate of progression of joint damage. Most placebo-controlled studies have failed to show a beneficial effect of slow acting antirheumatic drugs on radiological joint damage progression. However, comparative studies or analyses of cohorts of patients taking slow acting antirheumatic drugs show comparable amounts of progression for patients receiving gold and other drugs in this category. In addition, patients who show a clinical response also have less radiological progression after 6 months' therapy. In these circumstances, sulphasalazine produces comparable rates of radiological progression to those produced by gold and penicillamine. There are many problems associated with the use of radiological assessments to determine the progression of rheumatoid arthritis; thus, this method should not be deemed the most important technique by which to measure the success of therapy.

Side effect profile of 200 patients with inflammatory arthritides treated with sulphasalazine.

The side effect profile of sulphasalazine was documented in 200 patients with inflammatory joint disease treated with the drug for at least 1 year. Fifty-eight percent of patients developed one or more adverse reactions and in 21.5% the drug was withdrawn. A further 28% continued taking the drug at a reduced dose. Five percent of the side effects were judged to be potentially serious. In all patients the reactions subsided on either discontinuation of the drug or reduction of the dose. Gastrointestinal (33%) and central nervous system reactions (19%) were the most common, but all were relatively minor. Neutropenia (2%), thrombocytopenia (1%) and pan-hypogammaglobulinaemia (1%) were potentially the most serious effects. The side effect profile of sulphasalazine in inflammatory joint disease appeared to be similar to that in inflammatory bowel disease, but reactions were more frequent in inflammatory joint disease. Enteric-coated sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs, and in view of its established efficacy, its level of toxicity was found to be 'acceptable' as long as patients were carefully monitored and regular blood tests were carried out.

The influence of drugs and disease activity on biochemical and haematological data in rheumatoid arthritis.

Biochemical and haematological data from 218 patients with rheumatoid arthritis were analysed and compared with data from a reference hospital population. The comparison demonstrated significant differences in several biochemical and haematological tests and that the patterns of change are different between males and females. The data were also analysed by conventional statistical methods and discriminant analysis using a computer to establish which tests were most influenced by the activity of the disease and drug therapy. The results obtained demonstrate marked difference between groups of patients with different disease activity or receiving different drugs. The discriminant analysis also identified those tests which differentiate these groups most effectively.

Significance of the hydrogen ion concentration in synovial fluid in rheumatoid arthritis.

The hydrogen ion (H+) concentration and pCO2 were measured in the synovial fluid (SF) from the knee joints of 130 patients with arthritis by an acid-base analyser (ABL2 Acid-Base Laboratory), using a simple technique which prevented contact with air. H+ concentration was significantly higher in SF from 60 RA patients (mean 64.4 n mol/l; range 38-142 n mol/l) compared with patients with OA (mean 44 n mol/l; range 29-56 n mol/l), and 40 with other arthritides (mean 52 n mol/l). The H+ concentration in the SF showed a significant association with other variables of local inflammation-platelet, total leucocyte and polymorph counts, 5-nucleotidase, acid phosphatase and IgA levels in the SF and the clinical knee score, but not with the volume of the effusion. A similar relationship between these variables of inflammatory activity and SF pCO2 was also established. A higher SF H+ concentration was also found in systemically active disease, but no difference in SF pH between seropositive and seronegative patients. Whilst the pH of SF approximated to that of the blood in OA, it was significantly lower in the SF in RA. SF pH is a useful marker of local inflammatory activity, and its measurement is simple, reliable and rapid. It is relevant because changes in pH influence many of the processes involved in inflammation and the pH difference between SF and blood influences the transfer of drugs into the joint.

Risk factors for copper T IUD expulsion: an epidemiologic analysis.

Little is known of the factors associated with expulsion of intrauterine devices (IUD). We conducted a nested case-control study to examine the risk factors for copper T IUD expulsion using data from a multicenter international clinical trial. We included 70 cases with expulsion and 1,536 controls, and we examined a variety of characteristics of the IUD wearers. The proportional hazards model showed that young maternal age, abnormal amount of menstrual flow and dysmenorrhea before IUD insertion are risk factors for copper T IUD expulsion. The risk of expulsion steadily increased as age decreased, and as the severity of dysmenorrhea increased.

PIP: Data on 70 women who experienced expulsion of a copper releasing IUD were compared with data on 1536 women who still retained a copper releasing IUD to determine risk factors for IUD expulsion and calculate the magnitude of the association. The 18-40 year old women were part of an international multicenter clinical trial. Adolescents were at a 5.5 (unadjusted crude odds ratio) higher risk of IUD expulsion than women of at least 35 years old. The risk of expulsion decreased with age (odds ratio [OR] = 2.1 for 20-29 year olds and 1.1 for 30-34 year olds). Women whose menstrual flow was higher than normal were also at greater risk of IUD expulsion (OR = 2.4). The risk was the same for women who experienced severe pain during menstruation (OR = 2.4). The proportional hazards regression analysis showed maternal age (adjusted hazard ration = 5.4 for teenagers), amount of menstrual flow (2.4 for abnormal flow), and dysmenorrhea (1.8 for severe menstrual pain) were risk factors for expulsion of the copper releasing IUDs. Further, the trend test revealed a significant dose response pattern between maternal age and IUD expulsion (p .001) and between dysmenorrhea and expulsion (p = .011). The small sample size of nulliparous women (1 case and 7 controls) limited the ability of the analysis to identify parity as a risk factor which has been identified as a risk factor in other studies. In conclusion, these findings indicated that maternal age, amount of menstrual flow, and severe pain during menstruation are risk factors for expulsion of copper releasing IUDs.

Lymphocyte sub-populations and NSAIDs. Methodological aspects.

Activated lymphocytes can be enumerated as the less dense lymphocyte population (LDL) on a Ficoll density gradient column. The numbers of LDL are higher in rheumatoid arthritis (RA) but fall with successful second-line therapy; they correlate with active synovitis rather than with extra-articular disease. A cytospin technique has been developed which uses fewer cells than conventional suspension techniques and which allows further characterization of LDL using monoclonal antibodies. This confirms that these cells are relatively T-depleted but enriched in IA bearing cells, which may relate to homing patterns to the RA synovium. Using this technique, RA patients with active synovitis were shown to have more LDL and IA bearing cells, as were the active disease controls, including patients with other autoimmune disease (vasculitis) and with non-immune disease (sepsis). There were no differences between the ratios of T-suppressor to T-helper cells within these patient groups.

Case report: Klippel-Feil syndrome with coexistent hypoparathyroidism.

A 72-year old man presented with clinical signs of cervical myelopathy , a short neck, low posterior hairline, and limited neck movements. He also had a solitary kidney and anomaly of the third rib. Biochemical hypoparathyroidism with low parathyroid hormone level was discovered and secondary causes excluded. Treatment with alfacalcidol, calcium, and spinal decompression by complex laminectomy allowed complete recovery of symptoms. Klippel-Feil syndrome encompasses an increasing constellation of clinical features that affect most organs. The association with hypoparathyroidism, however, has not been described previously. This may be yet another syndrome with single pathology responsible for all the findings.

Sulphasalazine in rheumatoid arthritis: combination therapy with D-penicillamine or sodium aurothiomalate.

This open study examined the safety of adding a second slow-acting anti-rheumatic drug (SARD) - D-penicillamine or sodium aurothiomalate - to the therapy of 38 rheumatoid patients already established on sulphasalazine. Combined anti-rheumatic therapy given in this way was generally well-tolerated and the incidence of adverse reactions was not increased. During the first year none of the reactions were serious although 9 of the 29 patients (31%) given D-penicillamine and 3 of the 9 patients receiving aurothiomalate developed side-effects requiring withdrawal of the second SARD. Reactions attributed to D-penicillamine were: gastro-intestinal - 6, rashes - 2, and blurring of vision - 1. All 3 reactions occurring with gold were rashes, 2 associated with proteinuria and one with increased liver enzymes. During the second year D-penicillamine was withdrawn in 4 patients due to thrombocytopenia - 2, and rashes - 2. In addition an overall favourable clinical response was achieved in 70% of patients. This approach for combination therapy whereby a second SARD is given to patients already established on a single SARD, appears to minimise the toxicity which is a problem when 2 SARDs are started simultaneously.

Septic arthritis and thigh abscess after dilatation and curettage.

A previously fit 57-year old housewife who developed a septic arthritis of the right knee and abscess in the right thigh after dilatation and curettage is described. This is the first report of joint and soft tissue complications occurring together after this procedure. Despite antibiotic therapy which eradicated the joint infection, the abscess required surgical intervention. This illustrates the potential morbidity of septic complications after a minor surgical procedure.

The long term effects of sulphasalazine in the treatment of rheumatoid arthritis and a comparative study with penicillamine.

The long term efficacy and tolerability of sulphasalazine (SASP) in the treatment of 21 patients with active classical or definite rheumatoid arthritis (RA) were examined and compared with the effects of penicillamine in a similarly active group of RA patients. Nineteen of the 21 patients treated with SASP improved during the first 6 months as shown by significant changes in the clinical and laboratory variables. Clinical improvement was maintained for the remainder of the year. Improvement in laboratory variables was maintained at 9 months but showed some deterioration at 1 year. Six patients went into remission by the ARA criteria, and 16 were able to continue the drug at the end of 1 year. In addition SASP had a steroid-sparing effect in 4 of the patients on systemic steroids. No potentially dangerous side effects were encountered by the end of the first year, although 5 patients were withdrawn. Dyspepsia, nausea and abdominal discomfort were the most common side-effects, although rashes (3) and macrocytosis (2) also occurred. Eighteen of the 21 patients treated with penicillamine improved during 9 months, although there was some deterioration at 1 year. Eight patients were withdrawn because of side-effects - thrombocytopenia (5), nephrotic syndrome (1) and proteinuria (2). This study suggests that SASP has a disease modifying action maintained over a year and associated with low toxicity. It is a useful addition to the small number of second-line drugs with a possibly different mode of action.

Treatment of psoriatic arthritis with sulphasalazine: a one year open study.

Sulphasalazine (SASP) has recently become established as an effective treatment for active rheumatoid arthritis (RA), but has not previously been used in psoriatic arthritis in which remission-inducing drugs have proved disappointing. In this one year open study, 34 patients with active psoriatic arthritis were treated with sulphasalazine. An overall favourable clinical response was observed in 23 patients (67%). Nine patients (26%) achieved a very good therapeutic response and these either had arthritis associated with spondylitis or the symmetrical type of joint disease. Evaluation at 3, 6 and 12 months showed a significant improvement in inflammatory indices including a reduction in the C-reactive protein level and ESR. The drug was well-tolerated and side-effects were mild. Eight patients (23.5%) stopped the drug because of reactions and one patient with a rash was successfully desensitised. Fifty-three percent continued the drug into the second year. No apparent exacerbation of the psoriasis was observed. These results suggest that sulphasalazine is a safe and potentially effective drug in the treatment of psoriatic arthritis. A double-blind placebo-controlled trial has been set up to determine its true efficacy.

Randomized prospective comparison of laparoscopic and open peritoneal dialysis catheter insertion.

OBJECTIVE: To compare laparoscopic and conventional peritoneal dialysis catheter insertion with respect to post operative discomfort, complication rates, and catheter survival. DESIGN: Randomized prospective study. SETTING: Tertiary referral renal unit. PATIENTS: Fifty patients commencing peritoneal dialysis. INTERVENTION: Catheters were implanted laparoscopically or by a conventional surgical technique. MAIN OUTCOME MEASURES: The duration of surgery, hospital stay, pain scores, and analgesic requirements were recorded. Complications (early/late) and catheter survival were compared. RESULTS: The conventional procedure was faster than the laparoscopic (14.3 vs 21.9 minutes, p < 0.0001). There was no difference in any other parameter assessed. CONCLUSIONS: The data suggest that the insertion techniques are equivalent, and that laparoscopic insertion does not reduce early complication rates.

Investigation of phenylbutazone in synovial fluid.

1. Phenylbutazone was measured in the synovial fluid of 15 patients and found to be present in appreciable amounts which were related to plasma levels. 2. 80% of fluid levels were between 55% and 80% of those in plasma. 3. There was some evidence that in very actively inflamed joints phenylbutazone levels were lower. 4. There was no relationship to plasma or synovial fluid protein levels. 5. Phenylbutazone was found in one patient's synovial fluid three weeks after stopping the drug.