Mental health problems as a cause of long-term sick leave in the Norwegian workforce.

AIMS: There has been a growing concern about the proportion and socioeconomic consequences of work incapacity due to mental health problems. The aim of the present study was to describe the incidence and duration of different categories of mental health problems with at least two weeks of compensated absence from work in the general working population in Norway. METHODS: Cases were identified from files of the national medical insurance system, covering 90% of all employees, while census data were used for the denominators. Based on the International Classification of Primary Care, a total of 101,512 individuals with one or more long-term sick leaves (>2 weeks) due to psychological problems were identified in 1997 and 1998. RESULTS: Employees absent for psychological problems accounted for 16.8% of all incidences and 31.5% of all refunded sick days. The average one-year incidence was 2.47%, and was significantly higher for women (3.53%) than for men (1.66%). The incidence increased with increasing age, and more so for women than for men. The median duration of absence for all claimants was 79 days. Approximately 25% were back to work after one month, 52% after three months, while 8.5% had not returned to work after 12 months and were transferred to other forms of compensation. The length of sick leave varied considerably with diagnostic category, age, and gender. CONCLUSION: Mental health problems constitute a major health problem in the Norwegian workforce today. There is an urgent need for more knowledge about the effectiveness of interventions.

Continuing education meetings and workshops: effects on professional practice and health care outcomes.

BACKGROUND: Educational meetings and printed educational materials are the two most common types of continuing education for health professionals. An important aim of continuing education is to improve professional practice so that patients can receive improved health care. OBJECTIVES: To assess the effects of educational meetings on professional practice and health care outcomes. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register, MEDLINE (from 1966), the Research and Development Resource Base in Continuing Medical Education in January 1999 and reference lists of articles. SELECTION CRITERIA: Randomised trials or well designed quasi-experimental studies examining the effect of continuing education meetings (including lectures, workshops, and courses) on the clinical practice of health professionals or health care outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria, assessed the quality of each study, and extracted study data. We attempted to collect missing data from investigators. We conducted both qualitative and quantitative analyses. MAIN RESULTS: Thirty-two studies were included with a total of 36 comparisons. The studies involved from 13 to 411 health professionals (total N= 2995) and were judged to be of moderate or high quality, although methods were generally poorly reported. There was substantial variation in the complexity of the targeted behaviours, baseline compliance, the characteristics of the interventions and the results. The heterogeneity of the results was best explained by differences in the interventions. For 10 comparisons of interactive workshops, there were moderate or moderately large effects in six (all of which were statistically significant) and small effects in four (one of which was statistically significant). For interventions that combined workshops and didactic presentations, there were moderate or moderately large effects in 12 comparisons (eleven of which were statistically significant) and small effects in seven comparisons (one of which was statistically significant). In seven comparisons of didactic presentations, there were no statistically significant effects, with the exception of one out of four outcome measures in one study. REVIEWER'S CONCLUSIONS: Interactive workshops can result in moderately large changes in professional practice. Didactic sessions alone are unlikely to change professional practice.

Pulmonary dysplasia, Denys-Drash syndrome and Wilms tumor 1 gene mutation in twins.

While a genetic basis for the association of developmental lung and kidney defects has been suspected, the involvement of specific genes in this process is under active investigation. We report such a possible genetic linkage present in identical twins with a mutant Wilms tumor (WT1) gene. Twin girls, born at 35 weeks gestation, manifested symptoms of congenital nephrotic syndrome, renal failure, and severe respiratory abnormalities refractory to assisted ventilation. Both died at 1 month of age. Renal biopsies and autopsy kidney tissue from both the girls revealed diffuse mesangial sclerosis (DMS). Autopsy lung tissue revealed pulmonary dysplasia and hypoplasia in both twins. The WT1 gene from renal tissue in both twins was analyzed for mutations using polymerase chain reaction (PCR) amplification and the single-strand conformation polymorphism (SSCP) technique. Both twins possessed an identical missense mutation in exon 8 of the WT1 gene, resulting in replacement of arginine by histidine at amino acid 366 (arg366his) in the WTI protein. This mutation has previously been described in Denys-Drash syndrome. The WT1 gene plays a role in mesenchymal epithelial (ME) interactions in the developing urogenital system, and possibly has a similar role during lung morphogenesis. We propose that this WT1 gene mutation contributes to both DMS and developmental pulmonary abnormalities by altering ME interactions in both organs.

Utilization of technologies to reduce allogeneic blood transfusion in the United States.

Concern over safety of the blood supply has led to the use of technologies to reduce allogeneic blood transfusion. The objective of this research was to determine the utilization of these technologies in the United States. We evaluated the following techniques: preoperative autologous donation (PAD), cell salvage (CS) and acute normovolemic haemodilution (ANH); and the following pharmaceuticals: aprotinin (APR), epsilon-aminocaproic acid (EACA), tranexamic acid (TXA), desmopressin (DDAVP) and recombinant human erythropoietin (EPO). In 1997, we conducted a cross-sectional mail survey of service chiefs at 1000 US hospitals randomly selected and stratified by status as a provider of open-heart surgery, geographical location and hospital bed size. Sixty-nine per cent (690) of hospitals responded to at least one of the four surveys sent to each hospital. Hospitals reported use of techniques more than pharmaceuticals (P < 0.001); PAD (83%, n = 206) and CS (82% n = 420) were used most frequently. Lack of familiarity was the most common reason cited for infrequent use of pharmaceuticals. Organizational characteristics (e.g. provision of open-heart surgery, size, geographical location, teaching status and type of hospital) were differentially associated with technology use. There is greater use of techniques than pharmaceuticals in US hospitals to reduce the need for allogeneic blood in the peri-operative setting. Providing open-heart surgery is strongly associated with the utilization of these technologies.

Increased nuclear factor-kappaB and angiotensinogen gene expression in posttransplant recurrent focal segmental glomerulosclerosis.

In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IkappaBalpha, nuclear factor-kappaB (NF-kappaB), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients. Intra-graft NF-kappaB expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 + 55.6 ag/fg versus NON-FSGS 121.1 + 19.9, P=0.04) but not in acute rejection. NF-kappaB:IkappaBalpha ratios were higher in cadaveric donor versus living related donor recipients (15.7 + 2.8 vs. 8.8 + 1.3, respectively, P=0.015), and in African-American versus Caucasian recipients (15.6 + 2.9 vs. 9.1 + 1.3, respectively, P=0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 + 8.8 ag/fg R-FSGS vs. 16.0 + 4.7 NON-FSGS, P=0.009). We conclude that increased NF-kappaB and angiotensinogen gene expression are associated with R-FSGS. Increased NF-kappaB:IkappaBalpha ratios are associated with cadaveric donor recipients and African-American race.

Household income losses associated with ischaemic heart disease for US employees.

OBJECTIVE: To estimate the cost of lost work days due to ischaemic heart disease (IHD), and the cost of this reduced productivity using reduction in household income. DESIGN AND SETTING: Using 2 years of nationally representative observational data, this study examined the effect on household income of IHD. This effect was estimated after accounting for unemployment, days lost to illness and other effects of illness on the income of workers aged 18 to 64 years. MAIN OUTCOME MEASURES AND RESULTS: Previous measures of indirect costs of disease have typically not included the loss in productivity due to suboptimal work performance. Among workers in this age group, IHD was associated with a reduction of $US3013 in annual household income; this reduction was independent of occupational class, age, size of household and educational level. Such a reduction may be because of reduced on-the-job performance, employer perception of this, or unrelated lifestyle choices. It represents an estimated $US6.05 billion annual loss in productivity in 1992 dollars (or $US6.45 billion in 1996 dollars). CONCLUSIONS: Estimates of the indirect costs of chronic disease that do not account fully for the lost income of employees may significantly underestimate the benefits to employers and society of treatment and prevention.

Variations among hospitals in the quality of care for heart failure.

CONTEXT: Determining variations in quality of care among hospitals can help direct attention to poorly performing institutions. PRACTICE PATTERN EXAMINED: The proportion of patients with congestive heart failure meeting various quality criteria in 69 hospitals. HOSPITAL SELECTION: The hospitals were voluntary participants in a quality improvement program in five states (Colorado, Connecticut, Georgia, Oklahoma, and Virginia). PATIENT SELECTION: All patients with congestive heart failure discharged from the participating hospitals during a 15-month period in 1995 to 1996 (or, for hospitals with more than 50 eligible patients, a random sample of 50 patients). The total sample consisted of 2077 patients. DATA SOURCE: Documentation in the hospital medical record of left ventricular function, discharge medications, and discharge instructions. RESULTS: Left ventricular function was determined in 72% of patients (range across hospitals, 18% to 97%). Among patients with left ventricular systolic dysfunction, 79% were prescribed an angiotensin-converting enzyme inhibitor (range, 54% to 94%). Only 23% of the patients prescribed angiotensin-converting enzyme inhibitors received the target dose (range, 0% to 60%). Sixty-four percent of patients were counseled about the importance of a low-sodium diet at discharge (range, 25% to 97%), but only 8% were counseled about daily weight monitoring (range, 0% to 30%). CONCLUSION: Our results show substantial hospital-to-hospital variation in the quality of care for patients with heart failure.

The quality of care for Medicare patients with peptic ulcer disease.

OBJECTIVE: The aim of this study was to examine quality of care for hospitalized Medicare beneficiaries with peptic ulcer disease. METHODS: Collaborating with five Peer Review Organizations, we used 1995 Medicare claim files to select samples of inpatients with a principal diagnosis of peptic ulcer disease. Quality of care indicators developed by content experts included percentages for ulcer patients tested for Helicobacter pylori (H. pylori); biopsied patients who received tissue tests; H. pylori-positive patients who received appropriate therapy; and ulcer patients screened for preadmission nonsteroidal anti-inflammatory drug (NSAID) use and counseled about risks. RESULTS: Of 2,644 patients eligible for medical record review, 56% were tested for H. pylori, and 73% of those testing positive were treated appropriately; 84% of patients with endoscopic biopsies received a tissue test for H. pylori; 74% of patients were screened for preadmission NSAID use, 24% had documented counseling of NSAID use, and only 2% had documented counseling on the ulcer risk of NSAID use. Statistically significant regional variation occurred in four of six quality indicators. Outpatient records were reviewed for 529 patients to document prior outpatient H. pylori in this population; only 2% (n = 12) were tested for H. pylori in the year before admission. CONCLUSIONS: Opportunities exist to improve quality of care by testing for and treating H. pylori in hospitalized Medicare beneficiaries with peptic ulcer disease and to improve screening for NSAIDs and counseling on ulcer risks.

Web-enabled medical databases: a threat to security?

An increasing number of clinical databases are being adapted to allow access through Internet protocols, particularly Hypertext Transfer Protocol (HTTP). The World Wide Web (WWW) provides a user-friendly, standardized, broadly distributed database interface; at the same time, it may also present a threat to the security and confidentiality of patient data. However, there is little empirical evidence concerning such threats. Using publicly available records we estimate the additional risk of security violations due to web-enabling a database. The evidence, though limited, suggests that the additional risk may be small relative to more traditional security threats.

Mycophenolate mofetil in pediatric renal transplantation.

The use of mycophenolate mofetil (MMF) in adult renal transplantation has been associated with significantly decreased incidence of acute rejection. However, limited data are available for children after renal transplantation. A total of 67 patients undergoing renal transplantation at the University of Alabama at Birmingham, AL, USA and Children's Hospital of Boston, MA, USA were enrolled into the Cooperative Clinical Trials in Pediatric Transplantation randomized controlled trial of induction with OKT3 vs. i.v. cyclosporin A (CsA) at the time of transplantation. The first 31 patients entered were begun on azathioprine (AZA), 2 mg/kg on the first post-operative day. The subsequent 36 patients were begun on MMF, 1000 mg/m2/d. Other maintenance immunosuppression included oral CsA and Prednisone. Biopsy confirmation was obtained for all suspected rejection episodes. Glomerular filtration rate (GFR) was calculated using the Schwartz formula. Data were analyzed using Kaplan Meier survival curves and compared using log-rank tests. At the time of analysis, 52 patients (mean age 10.1 +/- 5 yr) had completed at least 12 months and 15 others had completed at least 6 months of follow-up post-transplantation. Of these, there were 39 male/28 female; 48 white/15 black/4 other; 49 living donor/18 cadaver donor. There were no significant differences in the incidence of rejection episodes, number of rejection episodes, the GFR at 6 and 12 months, allograft, or patient survival between patients receiving MMF vs. AZA. We could demonstrate no significant differences in these outcomes based on sex, race or induction therapy, leading to the conclusion that pediatric patients treated under a consistent protocol in two institutions have no improvement in short-term allograft outcome with the addition of MMF therapy.

Safety of kidney biopsy in pediatric transplantation: a report of the Controlled Clinical Trials in Pediatric Transplantation Trial of Induction Therapy Study Group.

BACKGROUND: Historically, young children undergoing renal transplantation have lower allograft survival than adults, and potential causes of this are being addressed by the North American Pediatric Renal Transplant Cooperative Study through the National Institutes of Health-sponsored study Cooperative Clinical Trials in Pediatric Transplantation. Included in this study is evaluation of surveillance renal biopsies (SB) and clinically indicated biopsies (CB). Few data exist in children to identify the risk involved with renal transplant biopsies. METHODS: Questionnaires were mailed to 21 participating centers asking for descriptions of adverse events associated with kidney biopsies, with choices limited to none, gross hematuria, perinephric hematoma, and other. Further clinical details were obtained from review of medical records of all patients with reported adverse events. Data were collected from 19 centers on 126 patients. RESULTS: Eighty-six patients had undergone 212 biopsies (75 SB and 137 CB). Nine biopsy-related adverse events were reported (4.2%): three SB (4.0%) and six CB (4.4%). Gross hematuria was reported in six patients (2.8%): two SB (2.7%) and four CB (2.9%). A perinephric hematoma was reported in one patient. Two patients with intraperitoneal kidneys developed significant bleeding after biopsy and required transfusions and surgical exploration. No patient lost kidney function or required nephrectomy after biopsy. No difference was noted in adverse events between SB at day 5 or 12 versus CB. CONCLUSION: Evaluation of transplanted kidney tissue may provide important information for the care of the transplantation patient. This analysis suggests that transplanted kidney biopsies can be performed with minimal risks in pediatric patients.

D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity?

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.

Early onset of nephrotic syndrome after treatment with D-penicillamine in a patient with Wilson's disease.

Wilson's disease responds to a variety of treatments including D-penicillamine and trientene. Nephrotic syndrome is a late complication of D-penicillamine treatment. We report a pediatric patient with Wilson's disease who developed nephrotic syndrome 2 wk after beginning D-penicillamine. His nephrosis resolved and his disease is quiescent with trientene treatment.

Meta analysis of the relationship between tuberous sclerosis complex and renal cell carcinoma.

The association of angiomyolipoma with tuberous sclerosis complex (TSC) patients is well recognised. Some literature has suggested that patients with TSC are at increased risk of renal neoplasm, particularly since angiomyolipomas can be locally invasive and demonstrate tumor like neovascularity on angiography. In an attempt to place in context one case of metastatic renal cell carcinoma in a patient with TSC a meta analysis of the literature was performed. One pediatric patient with TSC and metastatic renal cell carcinoma was evaluated. Reviews and case reports of TSC and renal cell carcinoma and related imaging findings were identified by searching the MEDLINE database, the 'bibliography of reviews' in Index Medicus, personal files and the reference lists from all identified reviews. Individual cases suitable for review in the available literature from 1922 through 1993 comprised the data base. The data base was analysed with the method of proportions and unpaired two-tailed Student's t-test for different populations. A cumulative summary of the literature amassed 107 additional cases from 62 reports over 71 years. Our case is the 17th case, to our knowledge, of renal cell carcinoma in TSC. Analysis of the distribution of characteristics and incidence of; renal cysts, renal cell carcinoma, and lymph node involvement demonstrate no increased risk of renal cell carcinoma in patients with TSC (P = NS). Though anecdotal evidence has suggested a relationship between TSC and renal cell carcinoma, meta analysis of cases of coincident TSC renal complex, cystic changes, angiomyolipoma and renal cell carcinoma implies an identical, though small, risk of malignancy in TSC patients as compared with the normal population.

Autosomal dominant distal renal tubular acidosis is associated in three families with heterozygosity for the R589H mutation in the AE1 (band 3) Cl-/HCO3- exchanger.

Distal renal tubular acidosis (dRTA) is characterized by defective urinary acidification by the distal nephron. Cl-/HCO3- exchange mediated by the AE1 anion exchanger in the basolateral membrane of type A intercalated cells is thought to be an essential component of lumenal H+ secretion by collecting duct intercalated cells. We evaluated the AE1 gene as a possible candidate gene for familial dRTA. We found in three unrelated families with autosomal dominant dRTA that all clinically affected individuals were heterozygous for a single missense mutation encoding the mutant AE1 polypeptide R589H. Patient red cells showed approximately 20% reduction in sulfate influx of normal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid sensitivity and pH dependence. Recombinant kidney AE1 R589H expressed in Xenopus oocytes showed 20-50% reduction in Cl-/Cl- and Cl-/HCO3- exchange, but did not display a dominant negative phenotype for anion transport when coexpressed with wild-type AE1. One apparently unaffected individual for whom acid-loading data were unavailable also was heterozygous for the mutation. Thus, in contrast to previously described heterozygous loss-of-function mutations in AE1 associated with red cell abnormalities and apparently normal renal acidification, the heterozygous hypomorphic AE1 mutation R589H is associated with dominant dRTA and normal red cells.

Effect of panel composition on physician ratings of appropriateness of abdominal aortic aneurysm surgery: elucidating differences between multispecialty panel results and specialty society recommendations.

OBJECTIVE: To investigate how the composition of multispecialty physician panels is associated with both the summary ratings assigned by such panels and the agreement of such panels with the recommendations of specialty societies. DATA SOURCES/STUDY SETTING: We examined the final ratings assigned by a nine-member multispecialty RAND Corporation physician panel regarding indications for abdominal aortic aneurysm surgery and the recommendations of a specialty society representing vascular surgeons who perform the same surgery. STUDY DESIGN: The panel was retrospectively divided into two sub-panels, one composed of the three vascular surgeons on the panel and the other composed of the six remaining physicians. We analyzed the two sub-panels' rating patterns with respect to each other and with respect to concurrent guidelines generated by the Joint Council of the Society of Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. PRINCIPAL FINDINGS: Of the 782 indications considered by the panel for appropriateness, the vascular surgeons had an average of mean ratings for appropriateness of 5.1, significantly higher than the 4.5 average of the other physicians. Across the 221 indications considered by the panel for necessity, the vascular surgeons had an average of mean necessity ratings of 6.8, significantly higher than the 5.8 average of the other physicians. The vascular surgeons' rankings of agreement with the guidelines of the Joint Council were significantly higher than those of the physician panelists from other specialties. CONCLUSIONS: statements of clinical appropriateness and necessity produced by summarizing ratings assigned to indications by expert panel members may disguise marked underlying disagreements among well-defined groups of practitioners within these panels. In the case of abdominal aortic aneurysm management, these disagreements within the RAND panel explain the marked discrepancy between the RAND multidisciplinary panel ratings and the recommendations issued by vascular surgeon professional societies.

The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling.

Autosomal recessive polycystic kidney disease (ARPKD) is a one of the most common hereditary renal cystic diseases in children. Its clinical spectrum is widely variable with most cases presenting in infancy. Most affected neonates die within the first few hours of life. At present, prenatal diagnosis relies on fetal sonography, which is often imprecise in detecting even the severe form of the disease. Recently, in a cohort of families with mostly milder ARPKD phenotypes, an ARPKD locus was mapped to a 13-cM region of chromosome 6p21-cen. To determine whether severe perinatal ARPKD also maps to chromosome 6p, we have analyzed the segregation of seven microsatellite markers from the ARPKD interval in 22 families with the severe phenotype. In the majority of the affected infants, ARPKD was documented by histopathology. Our data confirm linkage and refine the ARPKD region to a 3.8-cM interval, delimited by the markers D6S465/D6S427/D6S436/D6S272 and D6S466. Taken together, these results suggest that, despite the wide variability in clinical phenotypes, there is a single ARPKD gene. These linkage data and the absence of genetic heterogeneity in all families tested to date have important implications for DNA-based prenatal diagnoses as well as for the isolation of the ARPKD gene.

Autosomal recessive polycystic kidney disease: long-term sonographic findings in patients surviving the neonatal period.

OBJECTIVE: We studied the sonographic findings and the changes in renal function seen on long-term follow-up of children who had the initial diagnosis of autosomal recessive polycystic kidney disease made in the neonatal period. MATERIALS AND METHODS: The case records and sonograms of 14 children with biopsy evidence of autosomal recessive polycystic kidney disease were evaluated. Nine children who survived the neonatal period were followed up for a mean of 13 years (range, 5-19 years) after diagnosis and form the basis of this study. Serial changes in renal size, echogenicity, and function were assessed sonographically. The imaging findings were compared with those described in published reports. RESULTS: The sonographic findings showed that five of the nine children had a decrease in renal size, and three had stable renal size over a minimum follow-up period of 5 years. Only one of the nine survivors showed progressive increase in renal size. All had increased cortical echogenicity and large kidneys. Three patients showed a subjective change in renal echogenicity over time. A change in the echogenic pattern to one that resembles autosomal dominant polycystic kidney disease was noted with no evidence of increase in size of the kidneys. None of the surviving children had renal stones or massively enlarged kidneys. The renal function of seven of the nine survivors has remained stable with creatinine clearance nearly normal (> 60 ml/min/1.73 m2), and there was no correlation between renal size and renal function. CONCLUSION: In patients with autosomal recessive polycystic kidney disease who survive the neonatal period, kidney size as seen on sonograms does not continue to increase despite the patients' linear growth and maintained normal renal function. Rather, a decrease in kidney size and change in echogenicity occurs, producing a pattern that is similar to that seen on sonograms of patients with autosomal dominant polycystic kidney disease but without the marked increase in kidney size that occurs in that entity. This changing cystic pattern on follow-up sonograms may be the reason that previous descriptions of the sonographic findings in cases of autosomal recessive polycystic kidney disease have varied and why a decrease in size may not herald deteriorating renal function.