Repetitive transcranial magnetic stimulation over the supplementary motor area modifies breathing pattern in response to inspiratory loading in normal humans.

In awake humans, breathing depends on automatic brainstem pattern generators. It is also heavily influenced by cortical networks. For example, functional magnetic resonance imaging and electroencephalographic data show that the supplementary motor area becomes active when breathing is made difficult by inspiratory mechanical loads like resistances or threshold valves, which is associated with perceived respiratory discomfort. We hypothesized that manipulating the excitability of the supplementary motor area with repetitive transcranial magnetic stimulation would modify the breathing pattern response to an experimental inspiratory load and possibly respiratory discomfort. Seven subjects (three men, age 25 ± 4) were studied. Breathing pattern and respiratory discomfort during inspiratory loading were described before and after conditioning the supplementary motor area with repetitive stimulation, using an excitatory paradigm (5 Hz stimulation), an inhibitory paradigm, or sham stimulation. No significant change in breathing pattern during loading was observed after sham conditioning. Excitatory conditioning shortened inspiratory time (p = 0.001), decreased tidal volume (p = 0.016), and decreased ventilation (p = 0.003), as corroborated by an increased end-tidal expired carbon dioxide (p = 0.013). Inhibitory conditioning did not affect ventilation, but lengthened expiratory time (p = 0.031). Respiratory discomfort was mild under baseline conditions, and unchanged after conditioning of the supplementary motor area. This is the first study to show that repetitive transcranial magnetic stimulation conditioning of the cerebral cortex can alter breathing pattern. A 5 Hz conditioning protocol, known to enhance corticophrenic excitability, can reduce the amount of hyperventilation induced by inspiratory threshold loading. Further studies are needed to determine whether and under what circumstances rTMS can have an effect on dyspnoea.

Insomnia related to sleep apnoea: effect of long-term auto-adjusting positive airway pressure treatment.

Insomnia related to sleep apnoea (IA) is highly prevalent, and its proper treatment is still debated. The aim of this study was to test the hypothesis that long-term auto-adjusting positive airway pressure (APAP) treatment improves IA symptoms. 80 patients (mean±sd age 54.9±10.6 yrs, respiratory disturbance index (RDI) 45.0±24.6 events·h(-1)) receiving APAP treatment were followed prospectively for 24 months. Somnolence and depression were assessed at baseline (T0) with the Epworth and the QD2A scales, respectively. Nightly APAP use was measured after 24 months of treatment (T24). The assessment of insomnia at T0 and T24 used the insomnia severity index (ISI). The combination of ISIT0 ≥15 and ISIT0-ISIT24 ≥9 defined the APAP-responding insomnia (APAP-RI) group. A logistic regression analysis identified the factors independently associated with the APAP-RI group. The ISI (13.7±5.7 versus 8.2±6.3) decreased significantly from T0 to T24 (p = 0.0001) for the patients as a whole, with a mean decrease of 13.5±2.9. Among the 39 insomniac subjects (T0), 20 belonged to the APAP-RI group (51%). The Epworth score (OR 1.536, 95% CI 1.093-2.159; p = 0.01) and the RDI (OR 1.080, 95% CI 1.010-1.154; p = 0.02) increased the risk of belonging to the APAP-RI group. IA symptoms improved with APAP treatment, and improvement was associated with the initial severity of the disease and somnolence in our population.

A mathematical model of combined bacillus Calmette-Guerin (BCG) and interleukin (IL)-2 immunotherapy of superficial bladder cancer.

We report a mathematical model that describes the growth of superficial bladder cancer and the effect thereupon of immunotherapy based on the administration of Bacillus Calmette-Guerin (BCG) combined or not with interleukin-2 (IL-2). Intravesical instillations of BCG performed after surgical removal of tumors represents an established treatment with approximately 50% success rate. So far, attempts to improve this efficiency have not led to essential changes. However, convincing clinical results have been reported on the combination of IL-2 to BCG, even though this is still not applied in current practice. The present model provides insights into the dynamical outcomes arising in the bladder from the interactions of immune cells with tumor cells in the course of BCG therapy associated or not with IL-2. Specifically, from the simulations performed using seven ordinary and non-linear differential equations we obtained indications on the conditions that would result in successful bladder cancer treatment. We show that immune cells -effector lymphocytes and antigen-presenting cells-expand and reach a sustainable plateau under BCG treatment, which may account for its beneficial effect, resulting from inflammatory "side-effects" which eliminate residual or eventual newly arising tumor cells, providing thus protection from further cancer development. We find, however, that IL-2 does not actually potentiate the effect of BCG as regards tumor cell eradication. Hence, associating both under the conditions simulated should not result in more efficient treatment of bladder cancer patients.

Insomnia symptoms and CPAP compliance in OSAS patients: A descriptive study using Data Mining methods.

BACKGROUND: Obstructive Sleep Apnoea Syndrome (OSAS) and insomnia are common pathologies sharing a high comorbidity. CPAP is a cumbersome treatment. Yet, CPAP compliance must remain optimal in order to reverse excessive daytime sleepiness and prevent the cardiovascular consequences of OSAS. But chronic insomnia could negatively affect CPAP compliance. OBJECTIVE: To assess the consequences of insomnia symptoms on long-term CPAP use. METHODS: A prospective study was conducted on 148 OSAS patients (RDI=39.0+/-21.3/h), age=54.8+/-11.8years, BMI=29.1+/-6.3kg/m(2), Epworth Score=12.2+/-5.4, on CPAP. Using the Insomnia Severity Index (ISI) as an indicator of insomnia (ISI14=moderate to severe insomnia) and baseline data (anthropometric data, sleeping medication intakes, CPAP compliance, Epworth, Pittsburgh Sleep Quality and ISI scores, polygraphic recording data), Data Mining analysis identified the major rules explaining the features "High" or "Low ISI" and "High" or "Low Use" in the groups defined, according to the median values of the ISI and the 6th month-compliance, respectively. RESULTS: Median ISI was 15 and median 6th month-compliance was 4.38h/night. Moderate to severe insomnia complaint was found in 50% of patients. In the "High" and "Low ISI," the 6th month-compliance was not significantly different (3.7+/-2.3 vs 4.2+/-2.3h/night). In the classification models of compliance, the ISI was not a predictor of CPAP rejection or of long-term use, the predictor for explaining CPAP abandonment being the RDI, and the predictor of the 6th month-compliance being the one month-compliance. CONCLUSION: Insomnia symptoms were highly prevalent in OSAS patients, but had no impact on CPAP rejection or on long-term compliance.

Residual subjective daytime sleepiness under CPAP treatment in initially somnolent apnea patients: a pilot study using data mining methods.

BACKGROUND AND PURPOSE: Despite correct treatment with positive airway pressure (PAP), obstructive sleep apnea (OSA) patients sometimes remain subjectively somnolent. The reliability of the Epworth Sleepiness Scale (ESS) has been established for healthy subjects and patients under stable conditions; the ESS may eventually vary among treated OSA patients, biasing the results of a cross-sectional analysis of persisting sleepiness. The objective of this study was to depict the evolution of subjective vigilance under treatment using an index of ESS variability (DeltaESS). METHODS: In 80 OSA patients (apnea-hypopnea index [AHI]=54+/-26/h), initially somnolent (ESS=15+/-3) and treated with auto-titrating PAP (APAP) (oxyhaemoglobin desaturation index 3% [ODIapap]=3.4+/-2.2/h; daily APAP use=5.3+/-1.5 h) during 434+/-73 days, ESS scores were regularly collected four times every 109+/-36 days. DESS was calculated and data mining methods (Segmentation and Decision Tree) were used to determine homogeneous groups according to the evolution of ESS scores. RESULTS: When assessed cross-sectionally, 14-25% of the subjects were recognized as somnolent, depending on the moment when ESS was administered. Using data mining methods, three groups were clearly identifiable: two without residual somnolence - group 1, n=38 (47%), with high DeltaESS=-2.9+/-0.8, baseline ESS=16.3+/-3.3, AHI=58.5+/-26.1/h, mean ESSapap=5.1+/-2.4 and group 2, n=31 (39%), with low DeltaESS=-1.1+/-0.5, baseline ESS=13.2+/-1.4, AHI=53+/-27.3/h, mean ESSapap=8.8+/-1.9; and one with persisting sleepiness; group 3, n=11 (14%), with low DeltaESS=-0.3+/-0.8, baseline ESS=16.3+/-3, AHI=38.7+/-10.8/h, mean ESSapap=14.1+/-1.9. Compliance to PAP was high and comparable in the three groups. Age and body mass index (BMI) did not differ. CONCLUSION: Data mining methods helped to identify 14% of subjects with persisting sleepiness. Validation needs to be done on a larger population in order to determine predictive rules.

Evolution of health-related quality of life two to seven years after retropubic radical prostatectomy: evaluation by UCLA prostate cancer index.

To determine changes in health-related quality of life (HRQOL) in patients treated with retropubic radical prostatectomy (RP) between two and seven years after surgery. A questionnaire from the University of California Los Angeles Prostate Index was sent to 142 patients previously treated with retropubic RP as mono-therapy for clinically localized prostate cancer. Patients were divided into five groups according to time from surgery. Demographics, clinical and pathological characteristics of patients were compared between these groups. Correlation coefficients controlled for age at the time of questionnaire between HRQOL scores and time from RP were assessed. A total of 105 patients (74%) returned the questionnaire. The mean time from surgery was 48 months (range 25-84). Demographics, clinical and pathological characteristics of patients were not statistically different between time groups. Several recoding items were found to decrease significantly with the time from RP including physical functioning, role limitations due to physical health problem, vitality, and general health. In contrary, urinary, bowel and sexual scores were not significantly correlated to time from RP. Although sexual, urinary and bowel scores seem to remain stable from 2 to 7 years following RP, general health appears to significantly deteriorate with time after RP, independent of the patient's age at the time of the questionnaire.

[Sexual function after radical prostatectomy does not affect global patient satisfaction]. / La fonction sexuelle après prostatectomie radicale n'affecte pas la satisfaction globale des patients.

OBJECTIVES: To evaluate the quality of life after retropubic radical prostatectomy (RP) and its impact on global patient satisfaction concerning the treatment received. PATIENTS AND METHODS: 142 questionnaires were sent to patients treated for a localized prostate cancer by RP alone, with a minimum follow-up of 2 years. The questionnaire was the validated French version of the "UCLA-Prostate Cancer Index". A question concerning global patient satisfaction with treatment was added. RESULTS: 102 questionnaires were returned and analysed. The mean age of the patients at the time of RP was 63.8 years and the mean follow-up was 48 months. Evaluation of global satisfaction showed that 35/102 (343%) patients were very satisfied, 45/102 (44.1%) were satisfied, 15/102 had no opinion, 4/102 (3.9%) were dissatisfied and 3/102 (29%) were very dissatisfied. General quality of life scores ranged from 72 to 87 on a scale from 1 to 100 (where 100 corresponds to the best quality of life). For specific quality of life, the mean scores for sexual function and dysfunction were 27.5 and 25.1, respectively. The mean scores for urinary function and dysfunction were 72.5 and 67.8, respectively. Urinary function scores and seven of the nine general quality of life items were significantly correlated with better global patient satisfaction, but sexual function was not related to global satisfaction. CONCLUSIONS: Although sexual function is markedly altered after RP, it does not affect global patient satisfaction with the treatment received. Urinary function and general quality of life are significantly correlated with global satisfaction.