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Background and objectivesThe standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) includes androgen deprivation therapy (ADT), novel antihormonal therapies (NHT) and/or chemotherapy. Patients with newly diagnosed oligometastatic prostate cancer (omPCa) represent a distinct subgroup of mHSPC, for which the optimal treatment, particularly the role of radical prostatectomy (RP) and metastasis-directed therapy (MDT), is currently under debate.Materials and methodsIn this single center, retrospective analysis, 43 patients with newly diagnosed omPCa were included. All patients underwent RP as part of a multimodal, personalized treatment approach. Other treatments included ADT, NHT, MDT (surgery or radiotherapy), adjuvant radiotherapy (prostatic fossa and/or pelvic lymph nodes) or chemotherapy in various combinations. Clinical endpoints were progression free and cancer specific survival (PFS, CSS).ResultsNo patient with omPCa died from prostate cancer during an up to ten years follow-up period after intensified multimodal treatment i.e., RP, ADT, adjuvant radiation therapy and MDT (n=13). In contrast, patients requiring chemotherapy (n=10) showed a significantly worse PFS (p

Abstract Background Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and

Purpose: This study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM). Methods: Outcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS). Results: After PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27–0.56 vs. HR 0.50; 95% CI 0.30–0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50–1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30–0.98 vs. HR 0.49; 95% CI 0.29–0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34–2.06). Conclusion: The comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI. [ABSTRACT FROM AUTHOR]

Background: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.Methods: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression.Results: Both treatments resulted in substantial improvements at post (PeEx-I: dwithin  = 1.50, PeEx-S: dwithin  = 1.78) and follow-up (PeEx-I: dwithin  = 2.34; PeEx-S: dwithin  = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TRPeEx-I  = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse.Conclusions: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner. [ABSTRACT FROM AUTHOR]

Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925 [ABSTRACT FROM AUTHOR]

[Display omitted] • EET enhancement strategies in AD for treating refractory wastewaters are reviewed. • Applications of refractory wastewaters treatment by enhanced EET are discussed. • Prospects of enhanced treating refractory wastewaters based on EET are proposed. In anaerobic digestion (AD) system for the treatment of refractory wastewater, extracellular electron transfer (EET) by microorganisms is critical in influencing pollutant degradation and wastewater resourcing. However, when removing pollutants from refractory wastewater using AD technology, hydrolysis by extracellular enzymes is limited by EET efficiency, which often difficult to achieve their efficient degradation. Meanwhile, the anaerobic bacterial community was impacted by the toxicity of pollutants, which also affected the interspecies electron transfer, which seriously affected the effluent water quality and methane production. Therefore, intensifying the EET efficiency of the anaerobic system has become the key to break through the bottleneck of refractory wastewater treatment and resource utilization technology. In this paper, the EET mechanisms in the AD system for treating refractory wastewaters are summarized and a systematic review of EET intensification strategies for AD systems for treating refractory wastewaters, including EET from microorganisms to pollutants and electroactive bacteria to methanogens, is presented. In addition, this paper discusses in detail the application of EET based on enhanced treatment of refractory wastewaters containing pollutants with electron-absorbing groups (azo dyes, halogenated compounds, nitroaromatic compounds) and heavy metal oxides, and it also looks forward to the research direction and application prospect of regulating EET. This paper will provide a reference for treating and resourcing refractory wastewaters by AD technology. [ABSTRACT FROM AUTHOR]

Intensified treatment such as extended lymph node dissection (LND) and/or perioperative chemotherapy in addition to radical nephroureterectomy (RNU) has been suggested for high-risk cases of upper tract urothelial carcinoma (UTUC). We aimed to identify preoperative predictors of tumour stage and prognosis in the diagnostic work-up before RNU. Further to evaluate if our findings could be used in selecting patients for intensified treatment. A total of 179 patients treated with RNU for UTUC at Haukeland University Hospital (HUS) and Vestfold Hospital Trust (VHT) during 2005–2017 were included in this retrospective study. All relevant preoperative variables regarding the patient, the CT and the ureteroscopy (URS) were registered and analysed regarding their ability to predict non-organ confined disease (NOCD, pT3+ and/or N+) at final pathology after RNU. The prognosis was assessed calculating survival for the cohort and stratified by preoperative variables. Local invasion and pathological lymph nodes at CT predicted NOCD in uni and multivariate regression analyses (OR 3.36, p=.004 and OR 6.21, p=.03, respectively). Reactive oedema surrounding the tumour (OR 2.55, p=.02), tumour size (4.8 vs. 3.9 cm, p=.006) and high-grade tumour at URS biopsy (OR 3.59, p=.04) predicted NOCD at univariate regression analyses. The 5-year CSS and OS for the entire cohort was 79% and 60%. ECOG, local invasion, pathological lymph nodes and reactive oedema surrounding the tumour at CT predicted CSS. Several variables at the CT predicted both stage and survival. Local invasion at CT seems the most promising feature for selecting patients for intensified treatment. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the evidence-based treatments for PTSD are as effective in patients with CA-PTSD. Objective: We aimed to investigate the effectiveness of three variants of prolonged exposure therapy. Method: We recruited adults with CA-PTSD. Participants were randomly assigned to Prolonged Exposure (PE; 16 sessions in 16 weeks), intensified Prolonged Exposure (iPE; 12 sessions in 4 weeks followed by 2 booster sessions) or a phase-based treatment, in which 8 sessions of PE were preceded by 8 sessions of Skills Training in Affective and Interpersonal Regulation (STAIR+PE; 16 sessions in 16 weeks). Assessments took place in week 0 (baseline), week 4, week 8, week 16 (post-treatment) and at a 6-and 12-month follow-up. The primary outcome was clinician-rated PTSD symptom severity. Results: We randomly assigned 149 patients to PE (48), iPE (51) or STAIR+PE (50). All treatments resulted in large improvements in clinician assessed and self-reported PTSD symptoms from baseline to 1-year follow-up (Cohen’s d > 1.6), with no significant differences among treatments. iPE led to faster initial symptom reduction than PE for self-report PTSD symptoms (t135 = −2.85, p = .005, d = .49) but not clinician-assessed symptoms (t135 = −1.65, p = .10) and faster initial symptom reduction than STAIR+PE for self-reported (t135 = −4.11, p < .001, d = .71) and clinician-assessed symptoms (t135 = −2.77, p = .006, Cohen’s d = .48) STAIR+PE did not result in significantly more improvement from baseline to 1-year follow-up on the secondary outcome emotion regulation, interpersonal problems and self-esteem compared to PE and iPE. Dropout rates did not differ significantly between conditions. Conclusions: Variants of exposure therapy are tolerated well and lead to large improvements in patients with CA-PTSD. Intensifying treatment may lead to faster improvement but not to overall better outcomes. The trial is registered at the clinical trial registry, number NCT03194113, https://clinicaltrials.gov/ct2/show/NCT03194113

Background: It is unclear whether the evidence-based treatments for PTSD are as effective in patients with CA-PTSD. Objective: We aimed to investigate the effectiveness of three variants of prolonged exposure therapy. Method: We recruited adults with CA-PTSD. Participants were randomly assigned to Prolonged Exposure (PE; 16 sessions in 16 weeks), intensified Prolonged Exposure (iPE; 12 sessions in 4 weeks followed by 2 booster sessions) or a phase-based treatment, in which 8 sessions of PE were preceded by 8 sessions of Skills Training in Affective and Interpersonal Regulation (STAIR+PE; 16 sessions in 16 weeks). Assessments took place in week 0 (baseline), week 4, week 8, week 16 (post-treatment) and at a 6-and 12-month follow-up. The primary outcome was clinician-rated PTSD symptom severity. Results: We randomly assigned 149 patients to PE (48), iPE (51) or STAIR+PE (50). All treatments resulted in large improvements in clinician assessed and self-reported PTSD symptoms from baseline to 1-year follow-up (Cohen's d > 1.6), with no significant differences among treatments. iPE led to faster initial symptom reduction than PE for self-report PTSD symptoms (t135 = −2.85, p =.005, d =.49) but not clinician-assessed symptoms (t135 = −1.65, p =.10) and faster initial symptom reduction than STAIR+PE for self-reported (t135 = −4.11, p <.001, d =.71) and clinician-assessed symptoms (t135 = −2.77, p =.006, Cohen's d =.48) STAIR+PE did not result in significantly more improvement from baseline to 1-year follow-up on the secondary outcome emotion regulation, interpersonal problems and self-esteem compared to PE and iPE. Dropout rates did not differ significantly between conditions. Conclusions: Variants of exposure therapy are tolerated well and lead to large improvements in patients with CA-PTSD. Intensifying treatment may lead to faster improvement but not to overall better outcomes. The trial is registered at the clinical trial registry, number NCT03194113, • Childhood abuse-related PTSD can be effectively treated with (variants of) exposure therapy. • STAIR+PE and intensified PE did not improve treatment outcomes compared to PE.• Intensified PE showed faster symptom improvement. [ABSTRACT FROM AUTHOR]

To examine the effects of a multi-factorial, intensified treatment on self-reported health status, treatment satisfaction, and diabetes-related distress in screen-detected type 2 diabetes patients. Cluster-randomised controlled trial; A total of 498 screen-detected type 2 diabetes patients from 79 general practices were assigned to intensified ( n = 255) or routine treatment according to Dutch guidelines ( n = 243). At baseline and after 3 years, patients completed the Short Form-36 and the European Quality of Life-5 Dimensions questionnaires. After 4.5 years, patients completed the Diabetes Treatment Satisfaction Questionnaire and the Problem Areas In Diabetes scale. We analysed the effects of intensified treatment on self-rated health status, treatment satisfaction, and diabetes-related distress, using random effects models to account for clustering at practice level. Three to 5 years after type 2 diabetes was detected by screening, there were no differences between intensified and routine treatment in self-reported health status, treatment satisfaction, and diabetes-related distress. Multi-factorial, intensified treatment did not influence self-rated health status, treatment satisfaction, and distress in screen-detected type 2 diabetes patients. Therefore, health care professionals do not have to fear negative effects of an intensified treatment on these psychological outcomes. [ABSTRACT FROM AUTHOR]

SUMMARY Aims Autonomic neuropathy is a serious diabetic complication, probably contributing to the death of many young people with Type 1 diabetes mellitus. It is often not diagnosed. Methods Patients with Type 1 diabetes from the Stockholm Diabetes Intervention Study were investigated with power spectral analysis (n = 88), heart rate and blood pressure reactions to tilting (n = 66), and heart rate variability during deep breathing (n = 70) a mean of 11.4 years after randomization to intensified conventional treatment (ICT) or standard treatment (ST), the treatment groups similar with regard to age, duration of diabetes and metabolic control at baseline (HbA1c 9.4 (1.3)%, mean (sd)). Blood glucose levels (mean of 29 HbA1c values) during the 10 years were lower in the patients from the ICT group (7.2 (0.6) vs. 8.3 (1.0)%, P = 0.001). Results Heart rate variability (HRV) in the high frequency range (P = 0.034), the expiration–inspiration ratio (P = 0.020), and the brake index during tilt (P = 0.044) were lower in the ST group, indicating more pronounced parasympathetic insufficiency. Systolic blood pressure fell by 10 (16) mmHg in the ST group, and by 2.5 (15) mmHg in the ICT group 8 min after rising from the supine to a 70° upright position (P = 0.034). A decreased autonomic function was associated with age and higher HbA1c. Conclusion Better autonomic nerve function is associated with lower HbA1c and lower age which were both the same in the intensively and the conventionally treatment groups at baseline. After a mean of 11.4 years autonomic function was better in the intensively treated group. [ABSTRACT FROM AUTHOR]

Blood glucose values close to normal reduce the microvascular complications of insulin-dependent diabetes mellitus. The Stockholm study of this effect continued after the initial 7.5-year period in order to see what happened when intensively treated patients were left to control their own treatment while treatment was intensified in the control group. Forty-three patients with insulin-dependent diabetes randomised to intensified conventional treatment (ICT) and 48 patients randomised to standard treatment (ST) were followed-up for 10 years. Vascular complications, treatment side-effects and well-being were studied. Risk factors for complications were sought. HbA (normal range 3.9-5.7 %) was reduced from 9.5 ± 1.4 % (mean ± SD) in the ICT group and 9.4 ± 1.2 % in the ST group to a mean (during 10 years) of 7.2 ± 0.6 % and 8.3 ± 1.0 %, respectively ( p < 0.001). Serious retinopathy (63 vs 33 %, p = 0.003), nephropathy (26 vs 7 %, p = 0.012) and symptoms of neuropathy (32 vs 14 %, p = 0.041) were more common in the ST group after 10 years. HbA and age were the only risk factors for complications. Self-reported well-being increased to a greater degree and severe hypoglycaemia was more common in the ICT group. Cognitive function after 10 years was similar in both treatment groups, and was not related to the number of severe hypoglycaemic episodes. Intensified insulin treatment leads to reduced long-term complications and increased well-being without causing undue side-effects. [Diabetologia (1996) 39: 1483-1488] [ABSTRACT FROM AUTHOR]