Pneumonia in multiple injured patients: a prospective controlled trial on early prediction using clinical and immunological parameters

OBJECTIVE AND DESIGN: In a prospective trial 266 multiple injured patients were included to evaluate clinical risk factors and immune parameters related to pneumonia. METHODS: Clinical and humoral parameters were assessed and multivariate analysis performed. RESULTS: The multivariate analysis (odds ratio with 95% confidence interval (CI)) revealed male gender (3.65), traumatic brain injury (TBI) (2.52), thorax trauma (AIS(thorax) > or = 3) (2.05), antibiotic prophylaxis (1.30), injury severity score (ISS) (1.03 per ISS point) and the age (1.02 per year) as risk factors for pneumonia. The main pathogens were Acinetobacter Baumannii (40%) and Staphylococcus aureus (25%). A tendency towards higher Procalcitonin (PCT) and Interleukin (IL)-6 levels two days after trauma was observed for pneumonia patients. CONCLUSION: The immune parameters (PCT, IL-6, IL-10, soluble tumor necrosis factor p-55 and p-75) could not confirm the diagnosis of pneumonia earlier than the clinical parameters.     

Flexible versus rigid endoscopes for outpatient hysteroscopy: a prospective randomized clinical trial

To evaluate patient acceptance, optical properties and the clinical feasibility of flexible compared with rigid hysteroscopes, 142 patients undergoing outpatient hysteroscopy were included in a prospective, randomized clinical trial. The flexible hysteroscope was used in 70 patients, and the rigid instrument in 72. At different stages of the hysteroscopy the level of pain experienced by the women was assessed using a 10 cm visual analogue scale. Optical properties characterized by the parameters intrauterine visibility, hysteroscopic view and diagnostic accuracy were ranked by the surgeons using a 5-point scale (1 = excellent to 5 = insufficient), and duration of the hysteroscopy was measured. Hysteroscopy was successful in 87.5 and 100% of patients in the flexible and rigid groups respectively. With the use of rigid telescopes, discomfort at introduction and during the hysteroscopy was significantly greater (median 1.7 versus 0.7, P = 0.003; 3.1 versus 1.2, P < 0.001 respectively), but optical properties were judged to be far superior (P < 0.001 for all three comparisons) and procedure time was significantly shorter (median 70 versus 120 s, P = 0.003). In conclusion, outpatient hysteroscopy seems to be less painful when using flexible telescopes. However, rigid hysteroscopes provide superior optical qualities and permit a more rapid performance with higher success rates at much lower cost.     

Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial

We evaluated the efficacy of antithymocyte globulin for the treatment of moderate to severe aplastic anemia in a randomized controlled study. Eleven of 21 patients initially randomized to receive antithymocyte globulin (given intravenously on eight consecutive days) had sustained improvement in hematopoiesis within three months of treatment; none of 21 control patients who received supportive care alone improved (P = 0.0005). Six of 12 control patients who subsequently received antithymocyte globulin improved. Responders had gradual improvement in hematopoiesis, but none recovered completely normal peripheral-blood counts. The severity of bone-marrow failure, age, cause of aplastic anemia, and transfusion history had no apparent bearing on treatment outcome. The interval from diagnosis to antithymocyte globulin treatment correlated inversely with the chance of a treatment response, although this correlation was not statistically significant. These data indicate that antithymocyte globulin is effective in improving hematopoiesis in some patients with aplastic anemia.     

Induction of autologous graft-versus-host disease: results of a randomized prospective clinical trial in patients with poor risk lymphoma.

The results of blood or marrow transplantation in patients with chemorefractory aggressive lymphoma, that is, those not responding to conventional-dose chemotherapy at the time of transplant, have been poor. The relapse rate has been high after autologous bone marrow transplant, whereas allogeneic transplantation has been associated with excessive transplant-related toxicity. Administration of cyclosporine after autologous transplantation can induce an autoreactive syndrome that resembles graft-versus-host disease (GVHD). This syndrome, named autologous graft-versus-host disease, has clear antitumor activity in animal models that can be enhanced by the addition of cytokines such as gamma-interferon and interleukin-2. A randomized, prospective study was conducted to evaluate the antitumor effect of autologous graft-versus-host disease induced with cyclosporine, and augmented by the administration of gamma-interferon and interleukin-2 in patients with chemorefractory Hodgkin and aggressive non-Hodgkin lymphomas. Fifty-one patients were randomized, 24 to the autologous GVHD induction arm, and 27 to the noninduction arm after autologous transplant using mobilized peripheral blood stem cell (PBSC) grafts. There were no differences in treatment-related mortality, overall and event-free survival (OS, EFS) between both groups; however, in the induction arm, GVHD developed only in 4 patients. The administration of oral cyclosporine followed by interleukin-2 and gamma-interferon is generally not well tolerated, and does not appear to be an effective method to induce autologous GVHD in patients receiving autologous PBSC grafts.     

The usefulness of ultrasound guidance in frozen-thawed embryo transfer: a prospective randomized clinical trial

BACKGROUND: Recent randomized controlled trials have shown that implantation and pregnancy rates were improved with ultrasound-guided embryo transfer compared with clinical touch in fresh IVF cycles associated with supraphysiological ovarian steroid levels. However, the usefulness of ultrasound guidance in frozen-thawed embryo transfer where potential hormonal influences are lacking has not been appropriately investigated. METHODS: A total of 184 consecutive patients undergoing thawed embryo transfer cycles with hormone replacement under pituitary suppression were randomized by computer-generated randomization table to two study groups: 93 had ultrasound-guided (group 1) and 91 had clinical touch (group 2) embryo transfer. RESULTS: There was equal distribution between the two study groups with respect to the main demographic and baseline characteristics of the patients as well as the characteristics of both prior IVF cycles from which embryos were generated and cryopreserved-thawed embryo transfer cycles. However, both pregnancy and implantation rates in group 1 (34.4 and 19.8% respectively) were significantly higher than the corresponding values (19.7 and 11.9%) in group 2. CONCLUSIONS: Ultrasound guidance in frozen-thawed embryo transfer significantly increases pregnancy and implantation rates.     

Impact of a patient education program on adherence to HIV medication: a randomized clinical trial

Patients' knowledge of their HIV condition and its treatment, which has been recognized as a factor that influences adherence to antiretroviral therapy, can be improved through educational programs. This prospective, randomized, controlled trial compared an experimental group that participated in an educational program and a control group with standard care. The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy, patients' knowledge, quality of life, and therapeutic response in patients treated with highly active antiretroviral therapy. Three hundred twenty-six patients were analyzed at inclusion. A higher level of adherence was associated with patients who were older, had higher incomes, and did not smoke. CD4 cell count and plasma viral load were correlated with adherence at entry. The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months, which was maintained at 12 and 18 months. A delayed increase in adherence was observed in the control group at 12 months. No significant impact on quality of life was observed over time. The patients' health status improved in 56% of the experimental group subjects and 50% of the control subjects. However, no significant impact was shown on CD4 cell count and plasma viral load. This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy.     

Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial

Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP‐based genomic array profiling is a high‐resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP‐based array profiling in 104 MDS patients from the HOVON‐89 study. Oligo/SNP‐array identified all cytogenetically defined genomic lesions, except for subclones in two cases and balanced translocations in three cases. Conversely, oligo/SNP‐based genomic array profiling had a higher success rate, showing 55 abnormal cases, while an abnormal karyotype was found in only 35 patients. In nine patients whose karyotyping was unsuccessful because of insufficient metaphases or failure, oligo/SNP‐based array analysis was successful. Based on cytogenetic visible abnormalities as identified by oligo/SNP‐based genomic array prognostic scores based on IPSS/‐R were assigned. These prognostic scores were identical to the IPSS/‐R scores as obtained with karyotyping in 95%‐96% of the patients. In addition to the detection of cytogenetically defined lesions, oligo/SNP‐based genomic profiling identified focal copy number abnormalities or regions of copy neutral loss of heterozygosity that were out of the scope of karyotyping and fluorescence in situ hybridization. Of interest, in 26 patients we demonstrated such cytogenetic invisible abnormalities. These abnormalities often involved regions that are recurrently affected in hematological malignancies, and may therefore be of clinical relevance. Our findings indicate that oligo/SNP‐based genomic array can be used to identify the vast majority of recurrent cytogenetic abnormalities in MDS. Furthermore, oligo/SNP‐based array profiling yields additional genetic abnormalities that may be of clinical importance.     

qLessons learned from patients with access to an online self-management enhancing program for RA patients: Qualitative analysis of interviews alongside a randomized clinical trial

ObjectiveThis study aims to explain the earlier findings of a Randomized Controlled Trial (RCT), which showed that rheumatoid arthritis (RA) patients did not benefit from an online self-management program. Moreover, less patients than expected used the program.MethodsAs part of an explorative RCT, patients were interviewed to explore their (non) usage of the program. Purposive sampling (n = 21) was used to select patients from four groups of patients (n = 49): 1) non-users; 2) low users; 3) high users basic; 4) high users plus.ResultsThe program supported only a small group of patients because: 1) not all patients were motivated to use the program, 2) patients had no clear expectation or had differing expectations of the program, 3) there was a mismatch between individual patients’ support needs and the needs included in the program, 4) reminders were only sent to fill in the diaries for pain and fatigue, not to use the program modules.ConclusionThis study offers insights in the (non-) usage of online programs and how usage could be increased in practice.Practical implicationsHealth professionals should be involved in the implementation of this online programs and should inform patients what the program could bring them.     

Effects of a multidisciplinary cognitive rehabilitation program for patients with mild Alzheimer's disease

OBJECTIVE:

To evaluate the effects of a multidisciplinary rehabilitation program on cognition, quality of life, and neuropsychiatric symptoms in patients with mild Alzheimer''s disease.

METHOD:

The present study was a single-blind, controlled study that was conducted at a university-based day-hospital memory facility. The study included 25 Alzheimer''s patients and their caregivers and involved a 12-week stimulation and psychoeducational program. The comparison group consisted of 16 Alzheimer''s patients in waiting lists for future intervention.

INTERVENTION:

Group sessions were provided by a multiprofessional team and included memory training, computer-assisted cognitive stimulation, expressive activities (painting, verbal expression, writing), physiotherapy, and physical training. Treatment was administered twice a week during 6.5-h gatherings.

MEASUREMENTS:

The assessment battery comprised the following tests: Mini-Mental State Examination, Short Cognitive Test, Quality of Life in Alzheimer''s disease, Neuropsychiatric Inventory, and Geriatric Depression Scale. Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments.

RESULTS:

Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable, whereas controls displayed mild but significant worsening. The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer''s subjects. The treatment was also beneficial for the patients'' quality of life.

CONCLUSION:

This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer''s patients. We also observed a significant decrease in depressive symptoms and caregiver burden. These results support the notion that structured nonpharmacological interventions can yield adjunct and clinically relevant benefits in dementia treatment.     

Molecular testing for Trichomonas vaginalis in women: results from a prospective U.S. clinical trial

Trichomoniasis is a common sexually transmitted disease associated with preterm birth, low birth weight, and increased susceptibility to infection with other pathogenic sexually transmitted microorganisms. Nucleic acid amplification tests for Trichomonas vaginalis have improved sensitivity for detecting infected individuals compared to existing culture-based methods. This prospective, multicenter U.S. clinical trial evaluated the performance of the automated Aptima T. vaginalis assay for detecting T. vaginalis in 1,025 asymptomatic and symptomatic women. Vaginal swab, endocervical swab, ThinPrep PreservCyt, and urine specimens were collected. Subject infection status was determined by wet-mount microscopy and culture. Aptima T. vaginalis assay performance was determined for each specimen type by comparison to subject infection status. Of 933 subjects analyzed, 59.9% were symptomatic. Aptima T. vaginalis clinical sensitivity and specificity were, respectively, 100% and 99.0% for vaginal swabs, 100% and 99.4% for endocervical swabs, 100% and 99.6% in ThinPrep samples, and 95.2% and 98.9% in urine specimens. Aptima T. vaginalis performance levels were similar in asymptomatic and symptomatic subjects. This study validates the clinical performance of the Aptima T. vaginalis assay for screening asymptomatic and symptomatic women for T. vaginalis infection.     

Early rehabilitation outcome in patients with middle cerebral artery stroke

We aimed to evaluate the effect of arousal level in healthy subjects on P50 potential, as the variation in the level of arousal may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Eleven healthy volunteers participated in the study. A standard auditory P50 potential paradigm was applied. Two stimulation conditions were selected: eyes-open, i.e., high arousal level condition and eyes-closed, i.e., low arousal level condition. P50 component amplitudes in response to both the first (S1) and second stimulus (S2) of the pair, their ratio and difference were evaluated. P50 amplitude in response to S1 was significantly higher during the low arousal closed eyes condition as compared to high arousal open eyes condition. There was no P50 amplitude difference in response to S2 and no arousal effect on gating measures. This prompts for more careful evaluation of patients' arousal level when performing P50 studies and interpreting the results.     

Early rehabilitation outcome in patients with middle cerebral artery stroke

Although important data on the prognosis and rehabilitation outcome in stroke patients have been reported, data on functional recovery according to stroke subtypes are limited. This retrospective study aimed to evaluate functional outcome in patients with middle cerebral artery (MCA) stroke-the most common subtype of ischemic stroke. The records of stroke patients that underwent the rehabilitation program at our brain injury rehabilitation service between January 2007 and December 2008 were reviewed, and those with MCA stroke were included in the study. Patient demographic and clinical data, and Barthel Index (BI) and Functional Independence Measure (FIM) scores at admission and discharge were collected. The study included 80 MCA stroke patients with a mean age of 63.54 years. FIM and BI scores improved significantly post rehabilitation (P < 0.05). Age was negatively correlated with both BI and FIM scores at admission and discharge. Length of stay was not correlated with improvement in BI or FIM scores during hospitalization. The patients that had ≤1 month of inpatient rehabilitation had similar outcomes as those that had >1 month of inpatient rehabilitation (P > 0.05). Length of time after stroke onset was not correlated with BI or FIM scores at admission. Regardless of initial functional status, prediction of discharge functional status was misleading. Physiatrists should keep in mind that functional improvement does not always increase with duration of inpatient therapy.     

Determinants of patient participation in clinical studies requiring informed consent: why patients enter a clinical trial

In a survey on 26 clinical trials we have studied the reasons why some patients choose to participate in clinical trials while others decline. Interviews were held with 198 adult patients, just after they had been asked by the trial-clinician to participate. We interviewed patients who were asked to participate in a clinical trial, including those who decided not to participate. The theoretical guidelines to explain participation were based on an extended form of the Health Belief Model. Patients being asked to participate in a clinical trial decide by making a personal balance account. This comprises the physical and emotional added value patients hope to gain from the trial treatment compared to the non-trial treatment, minus the risks they expect in the trial and minus the extra time they expect the trial will take. The extent they feel physically threatened by their illness will also influence their decision. Furthermore, this personal balance account was found to depend on patient opinion about medical care and care-givers in general and on how patients regard their illness. Relatively long-term patients show a slightly different motivation to participate in a clinical trial than short-term patients. In line with the Health Belief Model, motivational beliefs on the relevance to reducing the threat to the patient's health condition ('values') and the evaluations of the clinical trial the patient is approached for ('expectancy'), are relevant in explaining patient behavior. Moreover, specific evaluative frames of reference are relevant in patients faced with the choice to participate or not. Suggestions are made to improve insight into patient motivation during the informed consent procedure of clinical trials.     

Long-term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily

Background:  The daily dose of aspirin in desensitization in aspirin-sensitive asthmatics with nasal polyps is still a matter of debate.
Aims of the study:  To compare two doses of aspirin during the first year of desensitization and to evaluate long-term effects on nasal/pulmonary symptoms.
Methods:  Patients with positive aspirin provocation test were treated with either 100 or 300 mg aspirin daily.
Results:  In all patients taking 100 mg aspirin ( n  = 7) recurrent nasal polyps were observed. No patient experienced reduction of asthma medication or improvement of pulmonary function. In the 300 mg group no recurrent nasal polyps were seen. Asthma medication could be reduced in three patients, pulmonary function was improved in five patients. Thirty-nine consecutively desensitized patients, taking 300 mg aspirin, showed significant improvement of olfaction and polyp-free nasal passages during the first year of therapy. After a median follow-up of 27 months no sinus revision surgery was necessary.
Conclusions:  Aspirin desensitization followed by 300 mg aspirin daily is efficacious and results in polyp-free nasal airways, improvement of sense of smell, and reduction of the need for sinus revision surgery for recurrent nasal polyps. Aspirin in a dose of 100 mg daily is not sufficient to effectively reduce nasal and bronchial or pulmonary symptoms and to prevent recurrent nasal polyps by at least the first 12 months of treatment.     

Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy

Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of 51Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m2 of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease.     

Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial

Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200?mg twice daily) for a period of 6–12?months and were followed for 6?months after the end of therapy (EOT). The primary endpoint was global success at 6?months, defined as complete or partial (≥50?% improvement) radiological response and mycological eradication. Forty-one patients with confirmed CPA were enrolled. All patients had A. fumigatus as the etiologic agent. By EOT, five patients had died from comorbidities and seven had discontinued voriconazole due to toxicity. The global success rate at 6?months was 13/41 (32?%): 10/19 (53?%) for chronic necrotizing aspergillosis and 3/22 (14?%) for chronic cavitary aspergillosis (p?=?0.01). The respective success rates at EOT were 58 and 32?%. Clinical symptoms and quality of life also improved during treatment. Voriconazole is effective for CPA, with acceptable toxicity. The response rate is higher and obtained more rapidly in necrotizing than cavitary forms.     

Oxygen saturation at rest,on exercise and during sleep in COPD patients undergoing pulmonary rehabilitation program. Two years prospective controlled study

The role of pulmonary rehabilitation (PR) in COPD patients is well established. However, the PR programs includes physical exercise that may deteriorate chronic hypoxemia. The objective of the study was to evaluate impact of a long term PR program on oxygen saturation at rest, on exercise and during sleep in COPD patients no receiving supplemental oxygenation. A two--year controlled study involved 27 rehabilitated (PR-COPD patients (6 females) aged 32-76 years, mean 58.1 years on average and 19 control (C-COPD patients (3 females) aged 58-83 years, mean 68. COPD patients participating in PR program patients were younger, had higher value of FVC and FEV1 and better results of METs during symptom-limited exercise test (ET, p = 0.007). They also had better results of transcutaneus oxygen saturation (SaO2) at rest (p = 0.02), a lower maximal decrease in SaO2 during ET(p = 0.003) and a higher value of medan SaO2 during (p = 0.02). Following PR program the number of METs achieved during ET increased in PR-COPD patients (p = 0.007) and did not change in C-COPD, p = NS. The SaO2 at rest did not change significantly in both groups. Maximal drop in SaO2 during ET decreased in PR-COPD patients (p = 0.02) and did not change in C-COPD(p = NS) group. Median SaO2 at sleep did not change in PR-COPD patients (p = NS) but it decreased in C-COPD patients (p = 0.02). The study indicates that long term PR does not deteriorate the resting diurnal hypoxaemia, it prevent COPD patients from time depending exacerbation of nocturnal hypoxaemia and can improve oxygen saturation on exertion. The results could be influenced by baseline differences between PR-COPD and C-COPD patients.