Development and psychometric properties of a disease-specific quality of life questionnaire for adult patients with growth hormone deficiency

BACKGROUND: Adults with growth hormone (GH) deficiency (GHD) may experience physical and psychological disturbances, which can affect their quality of life (QOL). OBJECTIVES: To develop and validate a disease-specific module from the previously published QOL measure Questions on Life Satisfaction Modules (QLS(M)): the QLS(M)-H that specifically addressed the needs of patients with hypopituitarism. A second aim was for the questionnaire to be applicable across different cultural backgrounds in order to evaluate the efficacy of therapy in large, international clinical trials, thus providing additional clinical endpoints for these studies. DESIGN: A preliminary German language version of the QLS(M)-H was developed from 26 semi-structured interviews of adults with GHD. The questionnaire was then independently translated into five other languages and applied in open, non-controlled, multicentre, longitudinal studies to patient (n=717) and normative populations (n=2700). METHODS: A revised, nine-item version of the questionnaire was developed, based on previously defined criteria, and was evaluated for reliability and validity. Sensitivity to detect changes after GH replacement was also assessed. RESULTS: The 16 items of the preliminary questionnaire were reduced to nine items on the basis of the correlation of items/factors from initial patient interviews. Psychometric analysis revealed the reliability of the nine-item scale. The Cronbach's alpha scores ranged from 0.81 to 0.89 and the test-retest correlations ranged from 0.76 to 0.88, all of which indicate reliability over time. Mean scores increased significantly during GH replacement therapy, with observed changes greater than those seen with the non-specific modules of the QLS(M), indicating the sensitivity of the scale. CONCLUSIONS: The QLS(M)-H questionnaire is concise, easy to complete, and can be effectively applied across different cultural backgrounds. Psychometric evaluation of the questionnaire reveals that it is a valid, reliable and sensitive tool useful for assessing impaired life satisfaction in adult patients with GHD and also for monitoring the efficacy of GH therapy.     

Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility

Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo.     

Postmortem age estimation via DNA methylation analysis in buccal swabs from corpses in different stages of decomposition—a “proof of principle” study

International Journal of Legal Medicine - Age estimation based on the analysis of DNA methylation patterns has become a focus of forensic research within the past few years. However, there is...     

R + C Factors and Sacro Occipital Technique Orthopedic Blocking: a pilot study using pre and post VAS assessment

Introduction:

The concept of a systematic or predictive relationship between distant vertebral levels distinct from accumulative functional compensatory mechanisms, such as in scoliosis, has been perpetuated within chiropractic technique systems based on clinical observation and experience. This study seeks to investigate this relationship between the cervical and lumbar vertebrae.

Methods:

Patients (experimental group n=26 and control group n=12) were selected from the patient base of one office, and were limited to patients that had sensitivity at specific cervical reflex points. Using a pre and post outcome measurement and sacro occipital technique R + C protocols, the related lumbar vertebra was adjusted in the direction indicated by the cervical vertebral sensitivity.

Results:

Statistical analysis revealed there was a statistically significant difference between pre- and post-VAS measurements and found that the notable difference in mean change in VAS scores were statistically significantly different between the experimental and control groups (p < .001).

Conclusion:

The findings of this study suggest that further research into cervical and lumbar vertebra interrelationships, and the efficacy of orthopedic block treatment, may be warranted. Further studies are needed to confirm whether a causal relationship exists between lumbar manipulation and decreased cervical spine sensitivity.     

Pulmonary function in patients with diabetes mellitus

BACKGROUND: Pulmonary complications of diabetes mellitus have been poorly characterized. Although some authors have reported normal pulmonary function, others found abnormalities in lung volumes, pulmonary mechanics, and diffusing capacity. SUBJECTS AND METHODS: We studied pulmonary function in a group of patients with diabetes using a combined cardiopulmonary exercise test. Twenty-seven patients with diabetes aged 48 +/- 13 years participated in the study. RESULTS: Overall, forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow, midexpiratory phase, were within the predicted values, but the residual volume/total lung capacity ratio was slightly elevated. Comparison by diabetes type showed nonsignificant differences in forced expiratory volume in 1 second and forced expiratory flow, midexpiratory phase. Residual volume/total lung capacity ratio was significantly elevated in type 1 patients compared with type 2. Carbon monoxide diffusion capacity (DLCO) was normal in both groups. There was no correlation between the results on pulmonary function test and duration of disease, presence of microangiopathy, or glycemic control. The DLCO was significantly lower in patients with microangiopathic changes, but not when DLCO was corrected for alveolar volume. On the cardiopulmonary exercise test, maximal workload, maximum oxygen uptake, and maximal heart rate were less than predicted, whereas anaerobic threshold and ventilatory reserve were normal. No significant differences were noted in diabetes type, and there was no correlation between parameters of cardiopulmonary exercise test and the other variables. CONCLUSION: Spirometric values are preserved in patients with diabetes mellitus, and there are no defects in diffusing capacity. Cardiovascular factors may account for impaired physical performance. There is no need for routine screening of pulmonary function among diabetic patients.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.