Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study

This prospective study investigated the effectiveness of a three-tier modularized out- and inpatient multidisciplinary integrated headache care program. N = 204 patients with frequent headaches (63 migraine, 11 tension-type headache, 59 migraine + tension-type headache, 68 medication-overuse headache and 3 with other primary headaches) were enrolled. Outcome measures at baseline, 6- and 12-month follow-ups included headache frequency, Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), standardized headache diary and a medication survey. Mean reduction in headache frequency was 5.5 ± 8.5 days/month, p < 0.001 at 6 months’ follow-up and 6.9 ± 8.3 days/month, p < 0.001 after 1 year. MIDAS decreased from 53.0 ± 60.8 to 37.0 ± 52.4 points, p < 0.001 after 6 months and 34.4 ± 53.2 points, p < 0.001 at 1 year. 44.0 % patients demonstrated at baseline an increased HAD-score for anxiety and 16.7 % of patients revealed a HAD-score indicating a depression. At the end of treatment statistically significant changes could be observed for anxiety (p < 0.001) and depression (p < 0.006). The intake frequency of attack-aborting medication decreased from 10.3 ± 7.3 days/month at admission to 4.7 ± 4.1 days/month, p < 0.001 after 6 months and reached 3.8 ± 3.5 days/month, p < 0.001 after 1 year. At baseline 37.9 % of patients had experience with non-pharmacological treatments and 87.0 % at 12-month follow-up. In conclusion, an integrated headache care program was successfully established. Positive health-related outcomes could be obtained with a multidisciplinary out- and inpatient headache treatment program.     

The current management of the neurogenic bladder in children with spina bifida

The urological care of the neurogenic bladder consists of 2 components: medical management with preservation of renal function and quality-oflife issues with achieving dryness and independence of bladder and bowel management. Both components are equally important for patients to live a healthy and fulfilled life. This report explores the diagnosis of the neurogenic bladder; quality-of-life issues that caregivers and patients should expect; the importance of primary care knowledge of the neurogenic bladder and treatment; surgical options; the transition of pediatric patients to adult care; and the importance of caregiver and patient understanding of their disease, treatment options, and responsibilities.     

Our initial experience with the technique of complete primary repair for bladder exstrophy

ObjectiveWe reviewed our initial results with complete primary repair of exstrophy in regard to continence status and the need for subsequent continence procedures.Patients and methodsWe performed a retrospective review of our surgical records from 1996 to 2008 to identify all patients with bladder exstrophy managed at our center.ResultsSixteen children were closed successfully. Six patients (37.5%) experienced complications: umbilical hernias in two, transient penopubic fistula in three, and subcoronal fistula due to meatal stenosis in one. Of the 12 males, seven (58.3%) were left with a hypospadias at the time of primary closure. Two (22.2%) children required a formal bladder neck reconstruction to achieve continence. Bladder augmentation and continent catheterizable stoma was performed in four cases (44.4%), and bladder neck injection in one case (11.1%). Bladder neck closure was also performed in another child following primary closure. Three of these children are continent and void spontaneously (33.3%). The remaining six require clean intermittent catheterization four to six times a day, resulting in four (44.4%) being continent. The number of continence procedures and mean number per patient were 15 and 1.66, respectively.ConclusionOur early experience with this technique has been encouraging, with few major complications, a highly successful closure rate and a cosmetically normal result.     

Inhalation of [123I]alpha1-protease inhibitor: toward a new therapeutic concept of alpha1-protease inhibitor deficiency?

The alpha1-protease inhibitor (alpha1-Pi) is separated from human serum and is therefore extremely expensive. Because only 2%-3% concentrates in the lung after intravenous administration, inhalational therapy for alpha1-Pi deficiency would seem likely to be better. The aims of this study were therefore to determine the pattern of deposition of inhaled alpha1-Pi labeled with 123I and measure the amount deposited in the lungs. METHODS: Eighteen patients with congenital severe alpha1-Pi deficiency were enrolled in the study. The low-specific-activity 123I-labeled alpha1-Pi aerosol (median particle size +/- SD, 3.9 +/- 2.5 microm) was generated by an air pressure-driven nebulizer. The patients inhaled for an average of 23.6 +/- 8.9 min. Static scintigrams in two projections were acquired immediately after (T1) and 1 (T2), 4 (T3), and 24 h (T4) after inhalation. The patients were divided into the following three groups according to their forced expiratory volume in 1 s (FEV1): group I, < or =40% of predicted normal (n = 8); group II, 40% < FEV1 < or = 60% of predicted normal (n = 4); group III, >60% of predicted normal (n = 6). RESULTS: The absolute percentage uptake values of alpha1-Pi in group I were 12.4 for T1, 7.3 for T2, 4.6 for T3, and 1.2 for T4; in group II the values were 13.0, 9.6, 6.2, and 2.0, respectively; and in group III, 14.6, 11.4, 6.5, and 3.6, respectively. Differences between the groups were generally statistically significant. Between T1 and T2, the probability value was <0.05 for group I versus group II, <0.006 for group I versus group III, and <0.39 for group II versus group III. Between T1 and T3, the probability value was <0.29 for group I versus group II, <0.22 for group I versus group III, and <0.94 for group II versus group III. Retention (between T1 and T4) was also dependent on the grade of the disease: P < 0.2 for group I versus group II, P < 0.001 for group I versus group III, and P < 0.02 for group II versus group III. Grading of the uptake pattern by three independent experienced investigators (87% agreement) revealed a peripheral deposition that was group dependent. We found that greater peripheral deposition corresponded with lower lung functional impairment: P < 0.5 for group I versus group II, P < 0.01 for group I versus group III, and P < 0.08 for group II versus group III. Degradation also corresponded with functional impairment: P < 0.05 for group I versus group II, P < 0.006 for group I versus group III, and P < 0.3 for group II versus group III. CONCLUSION: The results of this study show that sufficient amounts of alpha1-Pi can be deposited in the periphery of the lung by inhalation at least in patients with low-grade disease. Inhalation of alpha1-Pi may thus represent a new and more convenient route of drug administration.     

Association of a common AKAP9 variant with breast cancer risk: a collaborative analysis

Data from several studies have suggested that polymorphisms in A-kinase anchoring proteins (AKAPs), which are key components of signal transduction, contribute to carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we genotyped six nonsynonymous single-nucleotide polymorphisms that were predicted to be deleterious and found two (M463I, 1389G>T and N2792S, 8375A>G) to be associated with an allele dose-dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M463I, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M463I with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CI] = 1.08 to 1.27, P = .0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% CI = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI = 1.06 to 1.27, P = .001).     

Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol

Between 1996 and 2000, 90 newly diagnosed adult patients with T-acute lymphoblastic leukemia (T-ALL) were registered in the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acuta Limfoide (LAL) 0496 protocol. Cases were centrally processed for morphology, immunophenotype, cytogenetics, molecular biology, and multidrug resistance (MDR). Twenty-two patients were females and 68 were males. Four percent of cases were pro-T, 47% pre-T, 39% cortical T, and 10% mature T-ALL. Fifty-six percent of patients with pro-T + pre-T-ALL achieved complete remission (CR) compared with 91% for cortical + mature cases (P = .002). CD34 expression was associated with a significantly lower CR rate: 54% versus 84% (P = .009). Thirty-one (36.5%) of 85 patients had an abnormal karyotype, the most common abnormality (15%) being a partial del(6q). The cytogenetic profile did not impact on CR achievement. MDR1 function, present in 26% of cases, correlated significantly with CR achievement (P = .004). A highly significant (P = .001) difference in CR rate was observed between patients who did not express the CD13/CD33/CD34 antigens and were MDR functionally negative (96%) compared with patients positive for at least one of these markers (57%). Multivariate analysis showed an impact on CR achievement for CD33 expression and MDR1 function. An extensive biologic workup of adult T-ALL cases at presentation is recommended in order to design tailored therapeutic strategies aimed at improving CR rates.     

Sleep and cognition at baseline and the effects of REM sleep diminution after 1 week of antidepressive treatment in patients with depression

It has been hypothesized that non-rapid eye movement (NREM) sleep facilitates declarative memory consolidation, and rapid eye movement (REM) sleep is particularly important in promoting procedural learning. The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks. For our baseline, we chose 41 moderately depressed patients (age range 19-44 years), who were not taking antidepressants. In the morning after polysomnography, we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency, a shift of attention task and the Trail Making Test B. After recording baseline values, patients were assigned randomly to one of three treatment groups: medication with citalopram; medication with reboxetine; or exclusive treatment with psychotherapy. Retesting took place 1 week after onset of treatment. The main results were: (1) an association of slow-wave sleep with verbal memory performance at baseline; (2) a suppression of REM sleep in patients taking citalopram and reboxetine; (3) no differences regarding neuropsychological performance within the treatment groups; and (4) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine. In line with other studies, our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants.