Subjective Reasons for Non-Reporting of Adverse Drug Reactions in a Sample of Physicians in Outpatient Care.

INTRODUCTION: Drug safety surveillance strongly depends on the spontaneous reporting of adverse drug reactions (ADRs). A major limiting factor of spontaneous reporting systems is underreporting (UR) which describes incorrectly low reporting rates of ADRs. Factors contributing to UR are numerous and feature country-dependent differences. Understanding causes of and factors associated with UR is necessary to facilitate targeted interventions to improve ADR reporting and pharmacovigilance. METHODS: A cross-sectional questionnaire-based telephone survey was performed among physicians in outpatient care in a federal state of Germany. RESULTS: From n=316 eligible physicians n=176 completed the questionnaire (response rate=55.7%). Most of the physicians (n=137/77.8%) stated that they report ADRs which they have observed to the competent authority rarely (n=59/33.5%), very rarely (n=59/33.5%) or never (n=19/10.8%); the majority (n=123/69.9%) had not reported any ADRs in 2014. Frequent subjective reasons for non-reporting of ADR were (specified response options): lack of time (n=52/29.5%), the subjective evaluation that the required process of reporting is complicated (n=47/26.7%) or requires too much time (n=25/14.2%) or the assessment that reporting of an ADR is needless (n=22/12.5%); within open answers the participants frequently stated that they do not report ADRs that are already known (n=72/40.9%) and they only report severe ADRs (n=46/26.1%). DISCUSSION: Our results suggest a need to inform physicians about pharmacovigilance and to modify the required procedure of ADR reporting or to offer other reporting options.

Effects of division-synchronizing hypoxic and hyperthermic shocks upon Tetrahymena, a respiration and intracellular ATP concentration.

The division of Tetrahymena pyriformis GL cells was synchronized with either seven hypoxic or five hyperthermic (heat) shocks. Hyperthermic shocks of 34 degrees C produced no reduction in respiration rate and only a 19% decline in intracellular ATP concentration. Hypoxic shocks of 0.15% ambient oxygen concentration depressed intracellular ATP concentration 50%. It therefore appears that hypoxic shock, but not hyperthermic shock, reverses progress of Tetrahymena toward fission by reducing ATP concentration through a reduction of the rate of oxidative phosphorylation. After the first synchronized division, whether synchronized by intermittent hypoxia or hyperthermia, total respiration rate increased exponentially at the same rate of increase as total respiration rate in an exponentially growing (log phase) Tetrahymena cell culture. Before the first synchronized division, the total respiration rate increased exponentially but more slowly than after completion of the first synchronized division. The pattern of increase of total respiration during division synchronized by either procedure was different than the pattern of increase of total respiration of synchronous cells observed by Zeuthen.

Prevalence of diabetes and its complications in the Eastern Band of Cherokee Indians.

OBJECTIVE: To determine the prevalence of diabetes and selected complications among the Eastern Band of Cherokee Indians in North Carolina. RESEARCH DESIGN AND METHODS: Multiple IHS data systems were used to determine diabetes prevalence and complication rates. The RPMS was used to identify diabetes cases as of April 1989, degree of Indian inheritance, cardiovascular diseases (including hypertension), and retinopathy. Data on laser treatments and LEA were obtained from individual registries. Information on ESRD was obtained by a research assistant. The IHS Ambulatory Patient Care reporting system was used to calculate the number of diabetic patients for the years 1982-1987. The IHS user population was used as the denominator. Rates were age-adjusted to the 1980 U.S. population and diabetic population by the direct method. RESULTS: Using clinical records, the age-adjusted prevalence of diabetes in 1988 was 105.6/1000 people, four times the U.S. rate. Rates of diabetes were highest in the groups with the highest degree of Indian inheritance. LEAs occurred among diabetic patients at three times the rate for the U.S. Between 1985 and 1989, new cases of ESRD occurred at a crude annualized rate of 578/million, approximately six times the rate for U.S. whites. CONCLUSIONS: Diabetes presents a major burden to the Eastern Band of Cherokees. The limitation inherent in this study probably result in underestimation of the prevalence of diabetes and its complications in the community. Future studies are needed to assess the impact of medical and preventive programs on diabetes prevalence and complications in this community.

Infective exacerbations of chronic bronchitis: relation between bacteriologic etiology and lung function.

STUDY OBJECTIVE: In patients with severe COPD, acute infective exacerbations are frequent. Streptococcus pneumoniae and Haemophilus influenzae are the most commonly isolated bacteria in sputum cultures from these patients. We hypothesized that in patients with advanced disease, Gram-negative bacteria other than H influenzae play at least an equally important role. METHODS: We evaluated clinical data and sputum culture results from 211 unselected COPD patients admitted to our hospital with an acute infective exacerbation of COPD. One hundred twelve patients fulfilled our protocol criteria of reliable microbiologic results and reproducible lung function tests; the patients were categorized according to the recently published three stages of severity. RESULTS: Lung function tests revealed an FEV1 of > or =50% of the predicted value in 30 patients (stage I), an FEV1 of 35% to <50% of the predicted value in 30 patients (stage II), and an FEV1 of < or =35% of the predicted value in 34 patients (stage III). Bacteria were classified into three groups: group 1 contained S pneumoniae and other Gram-positive cocci; group 2, H influenzae and Moraxella catarrhalis; and group 3, Enterobacteriaceae and Pseudomonas spp. For all patients together, the most frequently isolated bacteria were group 3 organisms (Enterobacteriaceae and Pseudomonas spp, 48.2%), followed by group 1 organisms (S pneumoniae and other Gram-positive cocci, 30.4%), and group 2 organisms (H influenzae and M catarrhalis, 21.4%). In stage I patients, 14 of 30 had bacteria from group 1, seven of 30 had group 2, and nine of 30 had group 3. In stage II patients, eight of 30 had group 1 bacteria, 10 of 30 had group 2, and 12 of 30 had group 3. In stage III patients, 12 of 52 had group 1 bacteria, seven of 52 had group 2, and 22 of 52 had group 3. The three groups of bacteria causing infective exacerbations were unevenly distributed among the three severity stages of lung function (p=0.016). CONCLUSION: There is a correlation between deterioration of lung function and the bacteria isolated from patients with infective exacerbations of COPD. In acute infective exacerbations, Enterobacteriaceae and Pseudomonas spp are the predominant bacteria in patients with an FEV1 < or =35% of the predicted value.

Compartmental systems with pipes.

This paper presents a generalization of the classical compartmental models using the concept of "pipes" between the compartments and taking into account the time needed for the material to pass through these pipes. A general linear delay differential system describing such models is derived and some properties of its solutions-such as nonnegativity, boundedness, stability-are established. For stationary and asymptotically stationary systems the asymptotic solution is obtained, too. The theory presented generalizes several earlier results concerning more special equations.

Absolute levels of MDR-1, MRP, and BCL-2 MRNA and tumor remission in acute leukemia.

Mononuclear cells prepared from peripheral blood or bone marrow of 119 AML and 28 ALL patients prior and following therapy were analyzed for absolute transcript levels of the chemoresistance genes mdr-1 and MRP, and the proto-oncogene bcl-2, by validated contamination-protected quantitative RT-PCR. In newly diagnosed AML mainly tumors of the granulocytic lineage (FAB M1-M2) expressed increased mdr-1 mRNA amounts. The MRP gene was expressed in all investigated samples without relation to a particular FAB class. High initial expression of both genes did not confer a poor prognosis even at high number of CD34+ cells. Data compared prior to and after therapy start (paired samples) revealed that AML patients who did not respond to therapy (NR) expressed increased levels of mdr-1 mRNA, as well as MRP and bcl-2 cDNA normalized to GAPDH reference transcripts, when compared to patients achieving complete remission (CR; p = 0.003, 0.008 and 0.0005, respectively). In ALL-NR the mdr-1 and bcl-2 genes were entirely more active after induction chemotherapy. Arbitrary cut-off values were established in order to delimit pathological from non-pathological gene expression. 59% of studied AML and 33% of ALL-NR exceeded the arbitrary values (mdr-1: > 2 amol/microgram RNA, MRP: > 10 zmol/amol GAPDH, bcl-2: > 5 zmol/amol GAPDH) for one and 11% of AML-NR for two parameters. Only 17% of the AML-CR and none of the ALL-CR group were above these limits. The results indicate that high individual activity of usually one, rarely two of the investigated genes might be associated with poor clinical outcome in treated acute leukemia.

OpenLabs: the application of advanced informatics and telematics for optimization of clinical laboratory services.

OpenLabs has four major objectives: to improve the efficiency and effectiveness of clinical laboratory services by the integration of Knowledge Based Systems (KBSs) with Laboratory Information Systems (LISs) and equipment; to provide and implement standard solutions for Electronic Data Interchange (EDI) between laboratories and other medical systems; to specify a fully Open architecture for an integrated Clinical LIS and demonstrate the integration of various KBS modules on the open architecture platform; and to demonstrate the integration of OpenLabs modules with existing LISs.

Hypertrophic osteoarthropathy in a blesbok (Damaliscus dorcas phillipsi).

A 4.5-yr-old female blesbok (Damaliscus dorcas phillipsi) was radiographed following the appearance of lameness and swelling of the right front fetlock. Radiographic interpretation at that time was osteoarthritis caused by periosteal proliferation of the right metacarpus with periarticular osteophytes surrounding the fetlock. No treatment was initiated. Gradual abdominal enlargement over several months was interpreted as evidence of pregnancy. Six months after the initial lameness complaint, the blesbok suddenly collapsed and was unable to stand. Physical examination revealed a large firm mass occupying most of the abdomen that was found to be inoperable. Following exploratory laporotomy, the blesbok was euthanized. At necropsy, the mass weighed 17 kg. It had probably caused the animal's collapse. Histologically, the bony lesions of the right metacarpus, seen radiographically at the previous examination, were consistent with hypertrophic osteoarthropathy and may have been a sequela of the intra-abdominal mass.

Rickets in two hand-reared polar bear (Ursus maritimus) cubs.

Two polar bear (Ursus maritimus) cubs born at the Denver Zoological Gardens were abandoned by a primiparous mother. Lethargic and extremely chilled, the cubs were transported to the zoo hospital for intensive care and hand rearing. Both cubs developed rickets. Dietary changes were instituted, and both cubs completely recovered with the exception of a bowed right femur (genu varum) in the female cub.

[External irradiation of differentiated thyroid cancer: 30 follow up]. / A differenciált pajzsmirigyrákok külsö sugárkezelése: 30 év követés.

UNLABELLED: Following surgery which left no macroscopic residue 114 patients with differentiated thyroid cancer (58 papillary, 56 follicular) were subgrouped on the basis of the dose of prophylactic postoperative external radiation applied: group I--an adequate dose of radiation (greater than or equal to 4500 cGy of telecobalt, greater than or equal to 4000 R of orthovolt therapy); group II--an inadequate dose of radiation (including non-irradiated patients). Local/regional relapse-free survival (LRRFS), distant metastatic relapse-free survival (DMRFS) and total cause-specific survival (TCSS) were calculated by means of life-table analysis for both histologic types separately. Results. 1. TCSS and LRRFS were significantly (p less than 0.001) better for group I in papillary cancer. No difference was found in DMRFS. 2. LRRFS was significantly (p less than 0.001) better for group I in follicular cancer. No differences were found in TCSS and DMRFS. CONCLUSIONS: 1. The prophylactic postoperative external irradiation is an effective method for survival prolongation in papillary cancer, the local/regional recurrences thereby being reduced. 2. External irradiation, in conjunction with radioiodine treatment, should be considered in the postoperative management of follicular cancer to diminish local/regional relapse.

[The normal right-side electrocardiogram]. / A normális jobb mellkasi elektrokardiogram.

QRS complex, ST segment and T wave were investigated in V1R--V8R right chest wall leads in 122 healthy individuals (76 women, 46 men, mean age: 36.8 years). There was no Q wave in V1-3R. Going towards V8R, occurrence of QR and QS complexes increased. R/S ratio was the highest in V8R, while second r wave (r') was found to be most frequent (in 20.5%) in V6R. ST elevation at 80 msec after J point was found in all right chest wall leads, most frequently (in 91%) in V2R. All three forms of T wave morphology (positive, negative, isoelectric) were observed in these leads.

Post-transplant diabetes mellitus - risk factors and effects on the function and morphology of the allograft.

The incidence of post-transplant diabetes mellitus and its effects on the kidney allograft function and morphology were assessed. Patients were divided into three groups according to their glucose metabolism. Risk factors for diabetes were first assessed, and then changes in renal function were checked. Morphological changes in the allografts were examined by protocol biopsies. The overall incidence of diabetes was 16%. The development of diabetes was influenced significantly by the body mass index, the body weight and the age of the recipient. The incidence of diabetes was 8.6% in patients on cyclosporine A therapy and 28.8% in those on tacrolimus (p < 0.05). As to the morphology of the kidney, a significantly higher proportion of the biopsies showed severe interstitial fibrosis/tubular atrophy (p = 0.0004) and subclinical acute rejection ( p = 0.001) in the diabetic group compared to the normal one. This clinical study has revealed that the adverse effect of diabetes on the allograft can be detected with protocol biopsy before the manifestation of a functional deterioration.

Functional and histopathologic changes in renal transplant patients with new-onset diabetes and dyslipidemia.

BACKGROUND: The principal risk factors for cardiovascular mortality posttransplantation are hyperglycemia, hypertriglyceridemia, obesity, and smoking. METHODS: Among 115 patients, we assessed the risk factors for new-onset diabetes (NODM) and dyslipidemia (NODL), and their effects on the function and histopathologic changes in the allografts at 1 year posttransplantation. RESULTS: When evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal vs NODM patients (P=.004), normal versus NODL patients (P=.002), and normal versus NODL + NODM patients (P=.0001). The difference in body mass index (BMI) was significant when comparing normal with NODM + NODL patients (P=.003). In regard to immunosuppressive therapy, NODM was significantly more frequent among/prescribed tacrolimus (tac; P=.005), whereas subjects who received cyclosporine (CsA) showed a significantly higher incidence of NODL (P=.001). The triglyceride levels were 3.02 ± 1.51 mmol/L among those on CsA versus 2.15 ± 1.57 mmol/L for (P=.004). The difference also proved to be significant for total cholesterol level: 5.43 ± 1.23 mmol/L versus 4.42 ± 1.31 mmol/L respectively (P=.001). In regard to allograft function a significant difference was noted at 1 year after transplantation between the NODM + NODL and the normal group in serum creatinine level (P=.02) as well as the estimated glomerular filtration rate (P=.004). Among diabetic patients, the serum creatinine level measured at posttransplant year 5 was significantly higher than that in 1 year (212.43 vs 147.00 µmol/L; P=.0003). When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy in all 3 groups compared with normal function patients. CONCLUSION: Our clinical study suggested that at 1 year after transplantation allograft function is already impaired in the presence of both medical conditions (NODM and NODL). However, in regard to morphology, a single condition (NODM or NODL) was sufficient to produce histologic changes in the kidney.