Efficacy and safety of deep brain stimulation for treatment-refractory anorexia nervosa: a systematic review and meta-analysis

Background: Several pioneering studies investigated deep brain stimulation (DBS) in treatment-refractory anorexia nervosa (AN) patients, but overall effects remain yet unclear. Aim of this study was to obtain estimates of efficacy of DBS in AN-patients using meta-analysis. Methods: We searched three electronic databases until 1st of November 2021, using terms related to DBS and AN. We included trials that investigated the clinical effects of DBS in AN-patients. We obtained data including psychiatric comorbidities, medication use, DBS target, and study duration. Primary outcome was Body Mass Index (BMI), secondary outcome was quality of life, and the severity of psychiatric symptoms, including eating disorder, obsessive-compulsive, depressive, and anxiety symptoms. We assessed the risk of bias using the ROBINS-I tool. Results: Four studies were included for meta-analysis, with a total of 56 patients with treatment-refractory AN. Follow-up ranged from 6–24 months. Random effects meta-analysis showed a significant increase in BMI following DBS, with a large effect size (Hedges’s g = 1 ∙ 13; 95% CI = 0 ∙ 80 to 1 ∙ 46; Z-value = 6 ∙ 75; P < 0 ∙ 001), without heterogeneity (I2= 0 ∙ 00, P = 0 ∙ 901). Random effects meta-analysis also showed a significant increase in quality of life (Hedges’s g = 0 ∙ 86; 95% CI = 0 ∙ 44 to 1 ∙ 28; Z-value = 4 ∙ 01, P < 0 ∙ 001). Furthermore, DBS decreased the severity of psychiatric symptoms (Hedges’s g = 0 ∙ 89; 95% CI = 0 ∙ 57 to 1 ∙ 21; Z-value = 5 ∙ 47; P < 0 ∙ 001, I2= 4 ∙ 29, P = 0 ∙ 371). Discussion: In this first meta-analysis, DBS showed statistically large beneficial effects on weight restoration, quality of life, and reduction of psychiatric symptoms in patients with treatment-refractory AN. These outcomes call for more extensive naturalistic studies to determine the clinical relevance for functional recovery. This study is preregistered in PROSPERO,CRD42022295712

Five-year analysis on the long-term effects of dabrafenib plus trametinib (D + T) in patients with BRAF V600–mutant unresectable or metastatic melanoma

Background: First-line treatment with D+T demonstrated prolonged progression-free survival (PFS) and overall survival (OS) in patients with BRAF V600–mutant unresectable or metastatic melanoma. With 5 years of follow-up, we report survival and describe characteristics of patients in the phase 3 COMBI-d and COMBI-v trials with long-term benefit. Methods: Pooled 5-year landmark data for patients treated with D+T in the phase 3 COMBId (NCT01584648) and COMBI-v (NCT01597908) trials were analyzed. The trials enrolled patients with previously untreated BRAF V600E/K–mutant unresectable or metastatic melanoma. Patients received D 150 mg twice daily plus T 2 mg once daily vs either D + placebo (COMBI-d) or vemurafenib (COMBI-v). The primary endpoints were PFS in COMBI-d and OS in COMBI-v. Results: The pooled population included 563 patients who received D+T (COMBI-d, n = 211; COMBI-v, n = 352)

Patient perception of the benefit of a BRAF inhibitor in metastatic melanoma: quality-of-life analyses of the BREAK-3 study comparing dabrafenib with dacarbazine

Background: In a randomized phase III study (BREAK-3), dabrafenib showed prolonged progression-free survival (PFS) (median 5.1 versus 2.7 months; hazard ratio = 0.30; 95% confidence interval 0.18–0.53; P < 0.0001) compared with dacarbazine (DTIC) in patients with BRAF V600E metastatic melanoma. Assessing how these results are transformed into a real health benefit for patients is crucial. Methods: The EORTC QLQ-C30 questionnaire assessed quality of life (QoL) at baseline and follow-up visits. Results: For DTIC, all functional dimensions except role dimension worsened from baseline at follow-up. For dabrafenib, all functionality dimensions remained stable relative to baseline or improved at week 6; mean change in seven symptom dimensions improved from baseline, with appetite loss, insomnia, nausea and vomiting, and pain showing the greatest improvement. In the DTIC arm, symptom dimensions were unchanged or worsened from baseline for all symptoms except pain (week 6), with the greatest exacerbations observed for fatigue and nausea and vomiting. Mixed-model-repeated measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements from baseline in favor of dabrafenib for emotional and social functioning, nausea and vomiting, appetite loss, diarrhea, fatigue, dyspnea, and insomnia at weeks 6 and/or 12. After crossing over to dabrafenib upon progression (n = 35), improvements in all QoL dimensions were evident after receiving dabrafenib for 6 (n = 31) to 12 (n = 25) weeks. Conclusions: This first reported QoL analysis for a BRAF inhibitor in metastatic melanoma demonstrates that the high tumor response rates and PFS superiority of dabrafenib over DTIC is not only a theoretical advantage, but also transforms in a rapid functional and symptomatic benefit for the patient. Clinical Trials.gov identifier NCT01227889

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Metoda I-SCAN w ocenie nacisku wywieranego przez wyroby włókiennicze

The capabilities of the I-SCAN (TekScan) system for pressure measurements were tested in in vivo and in vitro condition using hosiery articles at a pressure of 18-21mmHg, as declared by the manufacturers. For two types of knee-length socks with the same structure and slight difference in composition (polyamide/elastomer 78/22% and 64/36%) the pressure was measured on the ankle and calf in four positions (1-front, 2-inner side, 3-back, 4-outer side). The highest pressure values were found for the 1-front position and the lowest for the 2-inner side position. It was shown that there is a correlation between the in vivo and in vitro tests. The I-SCAN method allows to take measurements in various place and to create maps of the pressure distribution.Nacisk wyrobów włókienniczych może powodować niepożądany wpływ na użytkownika lub działać profilaktycznie. W obu przypadkach ocena nacisku wymaga odpowiednich metod dostosowanych do przeznaczenia wyrobu. Badano możliwości systemu I-SCAN (TekScan) w warunkach in vivo i in vitro, na przykładzie wyrobów pończoszniczych należących do pierwszej klasy nacisku 18-21mmHg. W przeciwieństwie do powszechnie stosowanych metod, metoda I-SCAN bazująca na elastycznych matach pomiarowych umożliwia pomiar w dowolnym miejscu i tworzenie map nacisku. Dla dwóch rodzajów podkolanówek o zbliżonym składzie (poliamid/elastomer 78/22% i poliamid/elastomer 64/36%), i takiej samej strukturze zmierzono nacisk na wysokości kostki i łydki w czterech pozycjach (1–przód, 2-strona wewnętrzna, 3–tył, 4–strona zewnętrzna). Największy nacisk na kostce i łydce występował w pozycji 1-przód, a najmniejszy w pozycji 2-strona wewnętrzna. Wykazano, że dla metody I-SCAN istnieje korelacja między badaniami in vivo i in vitro

Sztywność zginania dzianin – porównanie metod badań

The bending stiffness of a textile is a feature determining comprehensive indicators such as fabric drapability and handle. Most methods of assessing the bending stiffness of textiles are based on the principle of the determination of the strain and force dependence. The simplest are methods involving the unidirectional straining force, which do not consider the anisotropy of the fabric’s physical properties. However, methods that allow the determination of multi-directional stiffness provide a more complete assessment. The aim of this work was to comparatively evaluate three testing methods that utilise different measurement principles. The experimental design included a unidirectional force action (PN-73/P0431), multidirectional force action (ASTM-D 4032-94), and bending stiffness testing by the direct determination of Young’s modulus by the method used at Kiev University. The methods analysed were assessed by statistical tests. Knitted fabrics with a net stitch were used as the test materials.Sztywność zginania materiałów włókienniczych jest jednym z parametrów kompleksowej oceny włókien oraz układalności i chwytu wyrobów. Większość metod, opisanych i stosowanych w laboratoriach włókienniczych, opiera się na zasadzie pośredniego określania sztywności przez wyznaczanie zależności odkształcenia i siły wywołującej te odkształcenia. Najprostsze są metody stosujące jednokierunkowe działanie siły, które nie uwzględniają anizotropii właściwości fizycznych wyrobu. Metody, które pozwalają określać wielokierunkową sztywność dają pełniejszą ocenę. Celem pracy była ocena porównawcza trzech metod badań uwzględniających różne zasady pomiaru. Program eksperymentu zawierał zasadę jednokierunkowego działania siły (PN-73/P0431), wielokierunkowe działanie siły (ASTM-D 4032-94) i badanie sztywności zginania przez wyznaczenie modułu Younga metodą zastosowaną w Kiev University .Ocenę metod dokonano na podstawie testów statystycznych. Materiał badawczy stanowiły kolumienkowe dzianiny o splocie siatki

Antybakteryjne włókniny filtracyjne modyfikowane polilaktydowymi mikrosferami zawierającymi triclosan

The paper analyses the properties of filter nonwovens modified with triclosan-containing microspheres in order to obtain antibacterial effects. The carrier of triclosan consists of microspheres made of degraded polylactide (PLA) that gradually releases triclosan, providing a uniform dosing of the antibacterial effect. The incorporation of triclosan-containing microspheres into the structure of nonwovens was carried out by padding or spraying a bath containing 2.5% or 5% microspheres. The antibacterial effect and influence of the modification on the air permeability of the filter nonwovens were assessed. The stability of the antibacterial effect was assessed on the basis of simulation tests with the use of a test stand operating with an air conditioner. Analysis of the results obtained showed that the modification used allows one to attain very good antibacterial properties. Better effects can be obtained with the use of the padding technique than by spraying. The simulation tests of nonwoven padded with a bath containing 5% of microspheres and performed with the use of an air conditioner showed that the antibacterial effect was stable for 12 months.Przedmiotem publikacji jest analiza właściwości włóknin filtracyjnych modyfikowanych mikrosferami z triclosanem, w celu uzyskania efektu antybakteryjnego. Nośnikiem triclosanu są mikrosfery z degradowalnego polilaktydu (Polylactide - PLA), który powoduje stopniowe uwalnianie triclosanu zapewniając równomierne dawkowanie działania antybakteryjnego. Wprowadzenie mikrosfer z triclosanem w strukturę włóknin wykonano metodą napawania i natryskiwania kąpielą zawierającą 2,5 i 5% mikrosfer. Dokonano oceny efektu antybakteryjnego oraz wpływu modyfikacji na przepuszczalność powietrza włóknin filtracyjnych. Trwałość efektu antybakteryjnego oceniono na podstawie symulacyjnych badań na stanowisku badawczym pracującym z urządzeniem klimatyzacyjnym. Analiza wyników wykazała, że zastosowana modyfikacja pozwala na uzyskanie bardzo dobrych właściwości antybakteryjnych. Lepsze efekty uzyskuje się przy zastosowaniu techniki napawania niż natryskiwania. Badania symulacyjne, na urządzeniu klimatyzacyjnym, włókniny napawanej kąpielą o stężeniu 5% mikrosfer, wykazały trwałość efektu antybakteryjnego w okresie ponad 12 miesięcy

Efficacy and safety of deep brain stimulation for treatment-refractory anorexia nervosa: a systematic review and meta-analysis

Background: Several pioneering studies investigated deep brain stimulation (DBS) in treatment-refractory anorexia nervosa (AN) patients, but overall effects remain yet unclear. Aim of this study was to obtain estimates of efficacy of DBS in AN-patients using meta-analysis. Methods: We searched three electronic databases until 1st of November 2021, using terms related to DBS and AN. We included trials that investigated the clinical effects of DBS in AN-patients. We obtained data including psychiatric comorbidities, medication use, DBS target, and study duration. Primary outcome was Body Mass Index (BMI), secondary outcome was quality of life, and the severity of psychiatric symptoms, including eating disorder, obsessive-compulsive, depressive, and anxiety symptoms. We assessed the risk of bias using the ROBINS-I tool. Results: Four studies were included for meta-analysis, with a total of 56 patients with treatment-refractory AN. Follow-up ranged from 6–24 months. Random effects meta-analysis showed a significant increase in BMI following DBS, with a large effect size (Hedges’s g = 1 ∙ 13; 95% CI = 0 ∙ 80 to 1 ∙ 46; Z-value = 6 ∙ 75; P < 0 ∙ 001), without heterogeneity (I2= 0 ∙ 00, P = 0 ∙ 901). Random effects meta-analysis also showed a significant increase in quality of life (Hedges’s g = 0 ∙ 86; 95% CI = 0 ∙ 44 to 1 ∙ 28; Z-value = 4 ∙ 01, P < 0 ∙ 001). Furthermore, DBS decreased the severity of psychiatric symptoms (Hedges’s g = 0 ∙ 89; 95% CI = 0 ∙ 57 to 1 ∙ 21; Z-value = 5 ∙ 47; P < 0 ∙ 001, I2= 4 ∙ 29, P = 0 ∙ 371). Discussion: In this first meta-analysis, DBS showed statistically large beneficial effects on weight restoration, quality of life, and reduction of psychiatric symptoms in patients with treatment-refractory AN. These outcomes call for more extensive naturalistic studies to determine the clinical relevance for functional recovery. This study is preregistered in PROSPERO,CRD42022295712

Patient perception of the benefit of a BRAF inhibitor in metastatic melanoma: quality-of-life analyses of the BREAK-3 study comparing dabrafenib with dacarbazine

Background: In a randomized phase III study (BREAK-3), dabrafenib showed prolonged progression-free survival (PFS) (median 5.1 versus 2.7 months; hazard ratio = 0.30; 95% confidence interval 0.18–0.53; P < 0.0001) compared with dacarbazine (DTIC) in patients with BRAF V600E metastatic melanoma. Assessing how these results are transformed into a real health benefit for patients is crucial. Methods: The EORTC QLQ-C30 questionnaire assessed quality of life (QoL) at baseline and follow-up visits. Results: For DTIC, all functional dimensions except role dimension worsened from baseline at follow-up. For dabrafenib, all functionality dimensions remained stable relative to baseline or improved at week 6; mean change in seven symptom dimensions improved from baseline, with appetite loss, insomnia, nausea and vomiting, and pain showing the greatest improvement. In the DTIC arm, symptom dimensions were unchanged or worsened from baseline for all symptoms except pain (week 6), with the greatest exacerbations observed for fatigue and nausea and vomiting. Mixed-model-repeated measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements from baseline in favor of dabrafenib for emotional and social functioning, nausea and vomiting, appetite loss, diarrhea, fatigue, dyspnea, and insomnia at weeks 6 and/or 12. After crossing over to dabrafenib upon progression (n = 35), improvements in all QoL dimensions were evident after receiving dabrafenib for 6 (n = 31) to 12 (n = 25) weeks. Conclusions: This first reported QoL analysis for a BRAF inhibitor in metastatic melanoma demonstrates that the high tumor response rates and PFS superiority of dabrafenib over DTIC is not only a theoretical advantage, but also transforms in a rapid functional and symptomatic benefit for the patient. Clinical Trials.gov identifier NCT01227889