Interictal sleep recordings during presurgical evaluation: Bidirectional perspectives on sleep related network functioning.

Sleep recordings are an integral part of presurgical evaluation in drug-resistant focal epilepsy. Physiological network functioning is substantially different between wakefulness and sleep and thus may add further complexity to the task of determining the epileptogenic zone (EZ). A thorough understanding of changes in epileptic networks in relation to sleep is therefore essential in order to fully appreciate the added value of sleep recordings. Furthermore, shared expertise in epilepsy and sleep is beneficial for both domains, as intracerebral EEG during presurgical evaluation offers a unique window into physiological networks and their interaction during sleep. This review intends to delineate the way in which sleep modifies interictal epileptic discharges (IEDs), and to summarize which sleep state is the most appropriate for aiding in discerning the EZ. Two approaches will be reviewed. First, classical scalp electroencephalography (EEG) recordings help to localize the EZ, especially during rapid-eye-movement (REM) sleep. REM sleep tends to narrow the field size of IEDs, and thus helps to target the core of the EZ. Second, automated analysis of intracerebral recordings can make use of both IEDs and sleep-related oscillations in combination. Notably, high frequency oscillations and directed connectivity measures can be assessed in a single sleep cycle and are valuable tools to probe epileptogenicity. In this approach, which exploits increased network interactions during sleep, non-REM-sleep is the most suitable sleep stage to extract multiple features of local and distributed neuronal activity in order to predict the EZ. The added value of intracerebral recordings is perfectly bidirectional. From a sleep perspective, invasive EEG recordings are a unique opportunity to unravel local sleep-related network function of superficial and deeply situated brain structures. Intracerebral EEG has thus allowed the dissection of sleep features and oscillations and their anatomical sources. A multicenter effort led by the Montreal Neurological Institute resulted in a detailed open-access atlas on normative EEG activity during sleep (https://mni-open-ieegatlas.research.mcgill.ca/). It contributed to our understanding that the human brain does not sleep uniformly but that specifically deep structures have distinct signatures that are discernable from the rest of the brain. Also, this research direction allowed us to gain insights into our understanding of the important neurocognitive functions of sleep. Finally, this review provides a clinical outlook on the benefit of genuine sleep recordings, i.e. recordings with additional sleep sensors, concomitant to presurgical evaluation, in order to fully discern common sleep disorders as a frequent comorbidity of epilepsy. In conclusion, shared expertise in sleep and epilepsy is of mutual added value for improving the management of patients with epilepsy.

Impact on quality of life in multiple sclerosis patients: Which urinary symptoms are to blame?

AIM: To evaluate the correlation between the Expanded Disability Status Scale (EDSS) in multiple sclerosis (MS) subjects, and the severity of lower urinary tract symptoms (LUTS), the bother caused by these symptoms and subjects' quality of life (QoL). MATERIAL AND METHODS: This cross-sectional study included 50 subjects with persistent LUTS secondary to MS who were recruited from the registry of a national NGO, between October 2017 and November 2019. Subjects with a history of any disease besides MS that could otherwise explain the presence of LUTS, as well as those with other neurological conditions were excluded. Information including MS duration, subjects' EDSS, voiding and storage LUTS, voiding symptoms' subscore of the International Prostate Symptom Score (IPSS-V), Overactive Bladder Symptom Scores (OABSS), Urinary Bothersome Questionnaire in Multiple Sclerosis (UBQMS), and urologic QoL (SF-Qualiveen) was gathered. Correlations between these scores were assessed using Spearman's bivariate correlations. Wilcoxon's signed rank test was used to evaluate the difference of impact between voiding and storage LUTS on bother of subjects. RESULTS: The median disease duration was 7±5.8years and the predominant lower urinary symptom was urgency (82%). Median OABSS and IPSS-V were respectively 8±3.8 and 8±3. Subjects were significantly more bothered from storage than voiding symptoms (2 vs. 1.6; P=0.03), and their QoL was directly affected by storage LUTS. Urgency urinary incontinence had the highest positive correlation with SFQ (r=0.542; P<0.01). MS duration and urologic QoL measured by SF-Q were negatively correlated (r=-0.345; P=0.01). CONCLUSION: In MS patients with LUTS, urologic QoL is mainly affected by storage urinary symptoms. Physicians should use a holistic approach to reduce the risk of complications in these patients, by controlling both voiding and storage symptoms, in particular urgency urinary incontinence that mostly affects patient's QoL.

Evaluation of Nd:YAG laser device efficacy on onychomycosis: a case series of 30 patients.

Until recently, pharmacologic molecules have been the only available treatments for onychomycosis. Laser treatments were introduced for recurrent or resistant cases or in patients in whom oral treatments are contra-indicated. Some devices were approved by the Food and Drug Administration (FDA). Neodymium yttrium aluminium garnet (Nd:YAG) is used for onychomycosis as a short-pulse or a long-pulse system. We aim to evaluate the efficacy of the short-pulse Nd:YAG in treating onychomycosis, its side effects, cure rates, and 12-month recurrence rates. Efficacy was evaluated based on a subjective measure of patient satisfaction on a scale from 1 to 10, and an objective measure based on the results of the mycologic cultures. Medical records of 30 patients were reviewed. Ages ranged from 22 to 85, with a mean of 44. Mycologic cure at 12 months was not achieved in 5 patients (16.67%) who had received laser treatment. None of these patients showed any signs of clinical improvement. Twenty patients (66.67%) were completely cured at 12 months, with corroborating negative mycologic cultures. The remaining five patients (16.67%) had discordance between their clinical cure status and their mycologic cultures. Side effects were reported by 7 patients out of 30 (33%): pain within 48 hours of the treatment session, burning sensation in the treated nail bed area. Our primary end point of negative mycologic cultures at 12 months was seen in 24 out of 30 (80%) of our patients. Similar culture cure rates have not been reported before, not even with systemic treatments with oral antifungals. However, few limitations should warrant us (False-negative results in fungal cultures; time limitation; sample size…). Still, we propose that this alternative should be offered for patients in whom antifungals are contraindicated or for patients previously treated, but not cured by oral antifungals, and in elderly and polymedicated patients.

Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer.

PURPOSE: To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm(3) (minimal dose to maximally exposed 2 cm(3)) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. METHODS AND MATERIALS: For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. RESULTS: Average doses to ALG and bladder points were 19.40 Gy ± 7.93 and 17.14 ± 8.70, respectively (p=0.01). The 2 cm(3) bladder dose averaged 24.40 ± 6.77 Gy. Ratios between D2cm(3) and dose points were 1.37 ± 0.46 and 1.68 ± 0.74 (p<0.001) for ALG and ICRU points, respectively. Both dose points appeared correlated with D2cm(3) (p<0.001) with coefficients of determination (R(2)) of 0.331 and 0.399 respectively. The estimated dose to the ICRU point of the rectum was 12.77 ± 4.21 and 15.76 ± 5.94 for D2cm(3) (p<0.0001). Both values were significantly correlated (p<0.0001, R(2) = 0.485). CONCLUSION: The ALG point underestimates the D2cm(3), but its mean on a large cohort is closer to D2cm(3) than the dose to ICRU point. However, it shows great variability between cases and the weak strength of its correlation to D2cm(3) indicates that it is not a good surrogate for individual volumetric evaluation of the dose D2cm(3).

Fractional laser for vitiligo treated by 10,600 nm ablative fractional carbon dioxide laser followed by sun exposure.

BACKGROUND: Vitiligo is an acquired disorder of the skin and mucous membranes. Many patients with vitiligo remain in the refractory state despite the availability of numerous potential treatments. To the best of our knowledge, only one trial considers ablative fractional CO2 laser in the treatment of vitiligo. OBJECTIVE: To investigate the effects of fractional CO2 laser followed by systemic sun exposure on non-segmental vitiligo (NSV). METHODS: Ten patients presenting refractory NSV were enrolled in this study. The patients underwent three sessions, one month apart, of fractional CO2 laser therapy on the affected areas of the skin (L-group). Five days after each laser treatment, patients were asked to expose themselves to the sun for 2 hours on a daily basis. Objective and subjective clinical assessments were performed at the beginning and at the end of the treatment. The L-group was then compared to a control group (C-group) that consisted of vitiligo lesions in the same patients but with sun exposure as the exclusive therapy. RESULTS: Compared to the C-group, the L-group showed better improvement in both objective and subjective assessments. There were no noticeable adverse events in terms of scarring and Koebner phenomenon among others. CONCLUSIONS: All patients treated with both, laser sessions and sun exposure, improved their chronic NSV lesions. Improvement was less significant in patients who exhibited vitiligo lesions over articular surfaces such as elbows and underarms. The best results were observed in vitiligo plaques located on the face, neck and legs. Consequently, fractional CO2 laser followed by sun exposure could be considered as an alternative modality for the treatment of refractory vitiligo, especially in sunny regions.

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy.

AIMS: To report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. MATERIALS AND METHODS: In 2003-2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan-Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. RESULTS: Of 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3-7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. CONCLUSION: In low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

Predictive factors for persistent and late radiation complications in breast cancer survivors.

PURPOSE: With improved diagnostic techniques and treatments of breast cancer, overall survival times are longer, giving more opportunity for normal tissue complications of treatment to manifest. Radiation late effects (RLEs) could have profound long-term impacts on the quality of life of the survivors. The aim of this study was to identify predictive factors influencing timing and types of complications in patients referred to the Adult Radiation Late Effects Clinic (ARLEC). METHODS: In a period of 16 years, 296 breast cancer patients were referred to the ARLEC. The clinical records were retrospectively studied to collect epidemiologic, medical and treatment data. Associations were sought between candidate predictive factors and time to the first complication after radiation treatment (RT) completion (primary outcome), and pain or swelling (secondary outcomes) using univariable and multivariable linear and logistic regression analyses. All analyses were performed in SAS, version 9.4. RESULTS: All patients were female with a mean age of 56.3 years. The first treatment-related complication occurred after a median of 3 months. Patients were followed at ARLEC for a median of 18 months. Older age and delay from surgery to RT (S-RT delay) were associated with earlier onset of complications (both p < 0.001). The most common complications were breast pain (62.1%) and swelling (45.9%). Histology and RT boost were associated with pain (p = 0.035 and 0.013). RT boost and S-RT delay on the other hand were associated with swelling (p = 0.013 and 0.005). CONCLUSIONS: Clinical factors identified could help recognize the patients at high risk for developing RLEs and alert physicians to initiate earlier diagnostic and therapeutic measures.

Restless legs syndrome among multiple sclerosis patients in Lebanon.

BACKGROUND: Multiple sclerosis (MS) is often associated with fatigue, with an increased prevalence of sleep disorders compared to the general population, notably restless legs syndrome (RLS). The aim of this study was to evaluate the prevalence and severity of RLS as well the co-occurrence of spinal demyelination lesions in patients with MS in Lebanon. METHODS: In this cross-sectional study, we consulted the MS database of the Lebanese association against Multiple Sclerosis and sent out questionnaires to 300 MS patients to screen then confirm the presence of RLS. The final sample included 28 MS participants with confirmed RLS. We conducted further questionnaires to collect demographic data, screen for comorbidities, gather spinal MRI results, and evaluate the severity of both diseases (using the EDSS and the JHRLSS). RESULTS: Prevalence of RLS was 15% among MS patients in our study. 46.4% of RLS-affected MS patients had spinal cord demyelination lesions on their MRIs. Participants with MRI lesions had a lower severity score on the JHRLSS (p = 0.088). No association was found between the EDSS results and JHRLSS, demographic data, or comorbidities. CONCLUSION: Restless legs syndrome is commonly found among patients with multiple sclerosis in Lebanon, is underdiagnosed, and ought to be systematically evaluated for in order to improve the patients' quality of life.

[Novel adverse effects of laser-assisted axillary hair removal]. / Nouveaux effets indésirables du laser dépilatoire axillaire.

BACKGROUND: Several adverse effects of depilatory laser may now be commonly expected in relation to skin type and anatomic location. We report and analyse unusual events in patients undergoing laser-assisted axillary hair removal, including hyperhidrosis, bromhidrosis and leukotrichia. OBJECTIVE: The aim of this study was to examine a large patient population, assess the frequency of these adverse effects, and establish a correlation with different hair-removal laser protocols. PATIENTS AND METHODS: A retrospective case-control study of patients undergoing laser-assisted axillary hair removal was conducted to determine the incidence of these adverse effects in relation to skin type and types of laser used. RESULTS: Hyperhidrosis, bromhidrosis and leukotrichia were seen in 11, 4, and 2% of patients respectively. Hyperhidrosis was significantly less frequent in patients with skin types III and IV than in those with skin type II or V. Combined diode and alexandrite laser sessions were associated with a significantly higher incidence of hyperhidrosis compared to diode or alexandrite sessions alone. Regarding bromhidrosis and leukotrichia, no significant correlation with age, skin type or laser settings was revealed by the statistical analysis. CONCLUSION: Hyperhidrosis, bromhidrosis and leukotrichia are likely new adverse effects of laser-assisted axillary hair removal.

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials.

AIMS: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. MATERIALS AND METHODS: The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. RESULTS: In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS. CONCLUSION: The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

K-complex-induced seizures in autosomal dominant nocturnal frontal lobe epilepsy.

OBJECTIVE: To examine in detail the relations between seizures and K-complexes in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). METHODS: Prolonged continuous video-EEG recording and analysis of 30 seizures in an 18-year-old woman suffering from ADNFLE with a CHRNA4 gene mutation. RESULTS: Twenty-seven of 30 recorded seizures started just after a K-complex. In nine cases a sound induced a K-complex that was immediately followed by the seizure. Most seizures preceded repetitive and brief ictal restarts. CONCLUSIONS: Three new characteristics have been observed in this ADNFLE patient: a K-complex is almost invariably present at seizure onset; sounds trigger some seizures; ictal restarts occur often. SIGNIFICANCE: These new observations--the presence of K-complexes at seizure onset and occurrence of sound-triggered seizures--support the view that ADNFLE seizures may be initiated by K-complexes.

Palbociclib in hormone receptor positive advanced breast cancer: A cost-utility analysis.

INTRODUCTION: The addition of palbociclib to letrozole improves progression-free survival in the first-line treatment of hormone receptor positive advanced breast cancer (ABC). This study assesses the cost-utility of palbociclib from the Canadian healthcare payer perspective. METHODS: A probabilistic discrete event simulation (DES) model was developed and parameterised with data from the PALOMA 1 and 2 trials and other sources. The incremental cost per quality-adjusted life-month (QALM) gained for palbociclib was calculated. A time horizon of 15 years was used in the base case with costs and effectiveness discounted at 5% annually. Time-to- progression and time-to-death were derived from a Weibull and exponential distribution. Expected costs were based on Ontario fees and other sources. Probabilistic sensitivity analyses were conducted to account for parameter uncertainty. RESULTS: Compared to letrozole, the addition of palbociclib provided an additional 14.7 QALM at an incremental cost of $161,508. The resulting incremental cost-effectiveness ratio was $10,999/QALM gained. Assuming a willingness-to-pay (WTP) of $4167/QALM, the probability of palbociclib to be cost-effective was 0%. Cost-effectiveness acceptability curves derived from a probabilistic sensitivity analysis showed that at a WTP of $11,000/QALM gained, the probability of palbociclib to be cost-effective was 50%. CONCLUSION: The addition of palbociclib to letrozole is unlikely to be cost-effective for the treatment of ABC from a Canadian healthcare perspective with its current price. While ABC patients derive a meaningful clinical benefit from palbociclib, considerations should be given to increase the WTP threshold and reduce the drug pricing, to render this strategy more affordable.

Quantifying Health Utilities in Patients Undergoing Stereotactic Body Radiation Treatment for Liver Metastases for Use in Future Economic Evaluations.

AIM: Stereotactic body radiation therapy (SBRT) is increasingly used as an option for those with liver metastases. In order to facilitate future economic impact of health technologies, health utility scores may be used. The EuroQOL-5D-3L (EQ-5D) preference-based healthy utility instrument was used to evaluate the impact of treatment with SBRT on health utility scores. MATERIALS AND METHODS: Between August 2013 and October 2014, 31 patients treated with 3-5 fractions of SBRT for liver metastases were enrolled in this study. The EQ-5D instrument was administered at baseline, during and up to 6 months post-SBRT. RESULTS: Mean EQ-5D score at baseline was 0.857, which remained stable across the entire study time period. Transient increases in difficulties with mobility (9.7% reported at baseline to 16.1% on the last day of treatment) and usual activities (3.2% reported at baseline to 34.5% on day two) were found during the course of treatment; these returned to baseline levels subsequently. The mean visual analogue score at baseline was 65.8 and remained unchanged throughout treatment and follow-up. CONCLUSIONS: The stability of health utility scores and problems reported by patients undergoing treatment indicate that SBRT for liver metastases does not impart a significant adverse effect on quality of life. These results may be used for future economic evaluation of SBRT.

Stereotactic Body Radiotherapy versus Low Dose Rate Brachytherapy for Localised Prostate Cancer: a Cost-Utility Analysis.

AIMS: To conduct a cost-utility analysis comparing stereotactic body radiotherapy (SBRT) with low dose rate brachytherapy (LDR-BT) for localised prostate cancer (PCa). MATERIALS AND METHODS: A decision-analytic Markov model was developed from the healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Health states included 'recurrence-free', 'biochemical recurrence' (BR), 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. A willingness-to-pay threshold of $50 000/QALY was used. RESULTS: SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $2615. Under base case conditions, our results were sensitive to the BR probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes marginally more effective with 0.009QALYs gained at a cost of $272 848/QALY. CONCLUSIONS: SBRT represents an economically attractive radiation strategy. Further research should be carried out to provide longer-term follow-up and high-quality evidence.