Estimating the prognostic value of cross-sectional network connectivity for treatment response in depression.

BACKGROUND: Tightly connected symptom networks have previously been linked to treatment resistance, but most findings come from small-sample studies comparing single responder v. non-responder networks. We aimed to estimate the association between baseline network connectivity and treatment response in a large sample and benchmark its prognostic value against baseline symptom severity and variance. METHODS: N = 40 518 patients receiving treatment for depression in routine care in England from 2015-2020 were analysed. Cross-sectional networks were constructed using the Patient Health Questionnaire-9 (PHQ-9) for responders and non-responders (N = 20 259 each). To conduct parametric tests investigating the contribution of PHQ-9 sum score mean and variance to connectivity differences, networks were constructed for 160 independent subsamples of responders and non-responders (80 each, n = 250 per sample). RESULTS: The baseline non-responder network was more connected than responders (3.15 v. 2.70, S = 0.44, p < 0.001), but effects were small, requiring n = 750 per group to have 85% power. Parametric analyses revealed baseline network connectivity, PHQ-9 sum score mean, and PHQ-9 sum score variance were correlated (r = 0.20-0.58, all p < 0.001). Both PHQ-9 sum score mean (ß = -1.79, s.e. = 0.07, p < 0.001), and PHQ-9 sum score variance (ß = -1.67, s.e. = 0.09, p < 0.001) had larger effect sizes for predicting response than connectivity (ß = -1.35, s.e. = 0.12, p < 0.001). The association between connectivity and response disappeared when PHQ-9 sum score variance was accounted for (ß = -0.28, s.e. = 0.19, p = 0.14). We replicated these results in patients completing longer treatment (8-12 weeks, N = 22 952) and using anxiety symptom networks (N = 70 620). CONCLUSIONS: The association between baseline network connectivity and treatment response may be largely due to differences in baseline score variance.

In vitro and in vivo digestibility of prebiotic galactooligosacharides synthesized by ß-galactosidase from Lactobacillus delbruecki subsp. bulgaricus CRL450.

BACKGROUND: The general assumption that prebiotics reach the colon without any alterations has been challenged. Some in vitro and in vivo studies have demonstrated that 'non-digestible' oligosaccharides are digested to different degrees depending on their structural composition. In the present study, we compared different methods aiming to assess the digestibility of oligosaccharides synthesized by ß-galactosidase (ß-gal) of Lactobacillus delbruecki subsp. bulgaricus CRL450 (CRL450-ß-gal) from lactose, lactulose and lactitol. RESULTS: In the simulated gastrointestinal fluid method, no changes were observed. However, the oligosaccharides synthesized by CRL450-ß-gal were partially hydrolyzed in vitro, depending on their structure and composition, with rat small intestinal extract (RSIE) and small intestinal brush-border membrane vesicles (BBMV) from pig. Digestion of some oligosaccharides increased when mixtures were fed to C57BL/6 mice used as in vivo model; however, lactulose-oligosaccharides were the most resistant to the physiological conditions of mice. In general ß (1→6) linked products showed higher resistance compared to ß (1→3) oligosaccharides. CONCLUSION: In vitro digestion methods, without disaccharidases, may underestimate the importance of carbohydrates hydrolysis in the small intestine. Although BVMM and RSIE digestion assays are appropriate in vitro methods for these studies, in vivo studies remain the most reliable for understanding what actually happens in the digestion of oligosaccharides. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The Precision in Psychiatry (PIP) study: Testing an internet-based methodology for accelerating research in treatment prediction and personalisation.

BACKGROUND: Evidence-based treatments for depression exist but not all patients benefit from them. Efforts to develop predictive models that can assist clinicians in allocating treatments are ongoing, but there are major issues with acquiring the volume and breadth of data needed to train these models. We examined the feasibility, tolerability, patient characteristics, and data quality of a novel protocol for internet-based treatment research in psychiatry that may help advance this field. METHODS: A fully internet-based protocol was used to gather repeated observational data from patient cohorts receiving internet-based cognitive behavioural therapy (iCBT) (N = 600) or antidepressant medication treatment (N = 110). At baseline, participants provided > 600 data points of self-report data, spanning socio-demographics, lifestyle, physical health, clinical and other psychological variables and completed 4 cognitive tests. They were followed weekly and completed another detailed clinical and cognitive assessment at week 4. In this paper, we describe our study design, the demographic and clinical characteristics of participants, their treatment adherence, study retention and compliance, the quality of the data gathered, and qualitative feedback from patients on study design and implementation. RESULTS: Participant retention was 92% at week 3 and 84% for the final assessment. The relatively short study duration of 4 weeks was sufficient to reveal early treatment effects; there were significant reductions in 11 transdiagnostic psychiatric symptoms assessed, with the largest improvement seen for depression. Most participants (66%) reported being distracted at some point during the study, 11% failed 1 or more attention checks and 3% consumed an intoxicating substance. Data quality was nonetheless high, with near perfect 4-week test retest reliability for self-reported height (ICC = 0.97). CONCLUSIONS: An internet-based methodology can be used efficiently to gather large amounts of detailed patient data during iCBT and antidepressant treatment. Recruitment was rapid, retention was relatively high and data quality was good. This paper provides a template methodology for future internet-based treatment studies, showing that such an approach facilitates data collection at a scale required for machine learning and other data-intensive methods that hope to deliver algorithmic tools that can aid clinical decision-making in psychiatry.

The Effectiveness of Low-Intensity Psychological Interventions for Comorbid Depression and Anxiety in Patients with Long-Term Conditions: A Real-World Naturalistic Observational Study in IAPT Integrated Care.

BACKGROUND: Low-intensity psychological interventions may be a cost-effective, accessible solution for treating depression and anxiety in patients with long-term conditions, but evidence from real-world service settings is lacking. This study examined the effectiveness of low-intensity psychological interventions provided in the Improving Access to Psychological Therapies programme in England for patients with and without long-term conditions. METHODS: A retrospective analysis was conducted on patients (total N = 21,051, long-term conditions n = 4024) enrolled in three low-intensity psychological interventions, i.e. Internet-delivered cognitive behavioural therapy (iCBT), guided self-help (GSH), and psychoeducational group therapy (PGT) within a Talking Therapies service from 2016 to 2020. Primary outcomes included pre-post-treatment changes in depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). RESULTS: Overall, both cohorts significantly improved on all outcomes post-treatment, with large effect sizes. Patients with long-term conditions experienced a greater reduction in depression while those without experienced a greater reduction in anxiety, but these differences were marginal (< 1 score difference on both measures). No difference between the cohorts was shown when comparing the differential effectiveness across interventions, but those engaging in iCBT showed greater reduction in depression and anxiety than those in GSH and PGT, while those in GSH improved more than PGT. CONCLUSIONS: Low-intensity psychological interventions, particularly iCBT, were effective in treating depression and anxiety in patients with long-term conditions in a real-world service setting. Our large-scale study supports the continued and increased implementation of low-intensity psychological interventions for this subpopulation via integrated care.

The relationship between posttherapeutic Cognitive Behavior Therapy skills usage and follow-up outcomes of internet-delivered Cognitive Behavior Therapy.

BACKGROUND: Clients independently applying Cognitive Behavior Therapy (CBT) skills is an important outcome of CBT-based treatments. The relationship between posttherapeutic CBT skills usage and clinical outcomes remains under-researched-especially after internet-delivered CBT (iCBT). OBJECTIVE: Explore contemporaneous and lagged effects of posttherapeutic CBT skills usage frequency on iCBT follow-up outcomes. METHOD: Nested within a randomized controlled trial, 241 participants received 8-week supported iCBT for anxiety and/or depression, completing measures of anxiety, depression, functional impairment, and CBT skills usage frequency at 3-, 6-, 9-, and 12-month follow-up. Cross-lagged panel models evaluated primary aims. RESULTS: While analyses support a contemporaneous relationship between anxiety, depression, functional impairment, and CBT skills usage frequency, no consistent lagged effects were observed. CONCLUSION: Findings align with qualitative research but the role of CBT skills usage in the maintenance of iCBT effects remains unclear. Innovative research modeling temporal and possibly circular relationships between CBT skill usage and clinical outcomes is needed to inform iCBT optimization.

Assessment of Obsessive Thoughts About COVID-19 in 7 Latin American Countries: Structure and Measurement Invariance of the Obsession With COVID-19 Scale.

The present study aimed to evaluate the measurement invariance of the Obsession with COVID-19 Scale (OCS) among seven Latin American countries: Bolivia, Brazil, Cuba, El Salvador, Guatemala, Paraguay, and Uruguay. Although the OCS has been used in several countries and languages, there is a need for approaches that better integrate the cross-cultural equivalence of the scale. A total of 3185 people participated in the study. The results indicated the presence of a unidimensional structure and good reliability indices for the OCS in each country. The alignment method indicated that the OCS is an invariant measure of COVID-19 obsession among the populations of seven Latin American countries. The findings based on IRT analysis indicated that all OCS items had adequate discrimination and difficulty parameters. The findings contribute to the understanding of the internal structure of the scale in different countries at the same time, something that has been pending evaluation.

Estimating Cost-Effectiveness Using Alternative Preference-Based Scores and Within-Trial Methods: Exploring the Dynamics of the Quality-Adjusted Life-Year Using the EQ-5D 5-Level Version and Recovering Quality of Life Utility Index.

OBJECTIVES: This study aimed to explore quality-adjusted life-year (QALY) and subsequent cost-effectiveness estimates based on the more physical health-focused EQ-5D 5-level version (EQ-5D-5L) value set for England or cross-walked EQ-5D 3-level version UK value set scores or more mental health recovery-focused Recovering Quality of Life Utility Index (ReQoL-UI), when using alternative within-trial statistical methods. We describe possible reasons for the different QALY estimates based on the interaction between item scores, health state profiles, preference-based scores, and mathematical and statistical methods chosen. METHODS: QALYs are calculated over 8 weeks from a case study 2:1 (intervention:control) randomized controlled trial in patients with anxiety or depression. Complete case and with missing cases imputed using multiple-imputation analyses are conducted, using unadjusted and regression baseline-adjusted QALYs. Cost-effectiveness is judged using incremental cost-effectiveness ratios and acceptability curves. We use previously established psychometric results to reflect on estimated QALYs. RESULTS: A total of 361 people (241:120) were randomized. EQ-5D-5L crosswalk produced higher incremental QALYs than the value set for England or ReQoL-UI, which produced similar unadjusted QALYs, but contrasting baseline-adjusted QALYs. Probability of cost-effectiveness <£30 000 per QALY ranged from 6% (complete case ReQoL-UI baseline-adjusted QALYs) to 64.3% (multiple-imputation EQ-5D-5L crosswalk unadjusted QALYs). The control arm improved more on average than the intervention arm on the ReQoL-UI, a result not mirrored on the EQ-5D-5L nor condition-specific (Patient-Health Questionnaire-9, depression; Generalized Anxiety Disorder-7, anxiety) measures. CONCLUSIONS: ReQoL-UI produced contradictory cost-effectiveness results relative to the EQ-5D-5L. The EQ-5D-5L's better responsiveness and "anxiety/depression" and "usual activities" items drove the incremental QALY results. The ReQoL-UI's single physical health item and "personal recovery" construct may have influenced its lower 8-week incremental QALY estimates in this patient sample.

Diagnosis and treatment of urethral stricture in men with neurogenic lower urinary tract dysfunction: A systematic review.

AIM: To summarize available data focused on diagnosis and management of urethral stricture in men with neurogenic lower urinary tract dysfunction by a systematic review of the literature. MATERIALS AND METHODS: A systematic review of the literature was carried out through an extensive electronic database search performed in PubMed/MEDLINE and Scopus databases for full texts, and International Continence Society, American Urology Association, and European Association of Urology abstracts for citations related to urethral structure. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. RESULTS: A total of 316 articles were identified, 48 of which were selected for this review. Different strategies are currently being used for the management of urethral strictures, such as clean intermittent catheterization (CIC) which reduces stricture by up to 68%; direct vision internal urethrotomy which shows lower rates of renarrowing; urethroplasty which shows a success rate up to 70%; urinary diversion is the treatment of choice when reconstruction is not possible. CONCLUSIONS: Further studies are needed in this population because of the heterogeneity of the outcomes and the lack of a standardized definition and classification of this population.

Durability of treatment effects following internet-delivered cognitive behavioural therapy for depression and anxiety delivered within a routine care setting.

OBJECTIVE: To investigate post-treatment relapse and remission rates 3, 6 and 9 months after completion of an acute phase of a clinician-supported internet-delivered cognitive-behavioural therapy (iCBT) for anxiety and depressive symptoms, within a routine care setting. METHOD: Secondary analysis from a 12-month pragmatic randomized-controlled trial delivered within the Improving Access to Psychological Therapies (IAPT) programme in England. Participants in the intervention arm were included if they met criteria for reliable recovery from depression (PHQ-9) and anxiety (GAD-7) at post-treatment assessment. Survival analysis was used to assess durability of treatment effects and determine predictors to relapse at 3-, 6- and 9-month follow-up. Hazard ratios predicting time-to-relapse were estimated with semi-parametric Cox proportional hazards model. RESULTS: Of the 241 participants in the intervention arm, 89 participants met the criteria for reliable recovery from depression and anxiety at the post-treatment assessment. Of these 89 eligible cases, 29.2% relapsed within the 9-month period, with 70.8% remaining in remission at 9 months post-treatment. Of those who relapsed, 53.8% experienced a relapse of depression and anxiety; 7.7% experienced a relapse of depression only; and 38.4% experienced a relapse of anxiety only. Younger age, having a long-term condition, and residual symptoms of anxiety at end-of-treatment were all significant predictors of relapse. CONCLUSIONS: This study is the first to explore the remission and relapse rates after an acute phase of iCBT treatment, within a routine, stepped-care setting. The results add to the scarce literature on the durability of the effects of iCBT treatment in routine care settings, where patients are not typically followed up after receiving a completed course of treatment.

Following up internet-delivered cognitive behaviour therapy (CBT): A longitudinal qualitative investigation of clients' usage of CBT skills.

BACKGROUND: While the acquisition and application of Cognitive Behaviour Therapy (CBT) skills is a core component and likely mechanism of effect maintenance in all CBT-based treatments, the extent of post-therapeutic CBT skills usage among internet-delivered CBT (iCBT) clients remains under-researched. METHOD: Nested within a pragmatic randomized controlled trial, 241 participants received an 8-week supported iCBT intervention for anxiety and/or depression and answered open-ended questions about their use and experience of CBT skills at 3-, 6-, 9-, and 12-month follow-up. Recurrent, cross-sectional qualitative analysis following the descriptive and interpretive approach was used to create a taxonomy, through which all qualitative data was coded. RESULTS: In total, 479 qualitative responses across 181 participants were analysed. Participants reported using a wide range of CBT skills and associated helpful and hindering experiences and impacts. The reasons for discontinued CBT skills usage were diverse, ranging from rare adverse effects to healthy adaptation. CONCLUSION: The study shows how clients receiving iCBT in routine care learn CBT skills during treatment and utilize them in productive ways post-treatment. Findings coincide with similar research in face-to-face CBT and may inform future research to drive innovation and iCBT intervention development.

Time-dependent depression and anxiety symptoms as risk factors for recurrent cardiac events: findings from the UPBEAT-UK study.

BACKGROUND: Depression is a well-known risk factor for recurrent cardiac events (RCEs) but findings are less consistent for anxiety, not previously reported on using a time-dependent approach. We aimed to study the prognostic effect of anxiety and depression symptom levels on RCEs. METHODS: Data (N = 595) were drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Hospital Anxiety and Depression Scale symptoms were grouped into: agitation (three items), anxiety (four items), and depression (seven items) subscales. We performed two types of multivariate analyses using Cox proportional hazard models with delayed entry: with baseline variables (long-term analysis), and with variables measured 12-to-18 months prior to the event (short-term time-dependent analysis), as RCE risk factors. RESULTS: In the baseline analysis, both anxiety and depression, but not agitation, were separate RCE risk factors, with a moderating effect when considered jointly. In the short-term time-dependent analysis, elevated scores on the anxiety subscale were associated with increased RCE risk even when adjusted for depression [hazard ratio (95% confidence interval) 1.22 (1.05-1.41), p = 0.009]. Depression was no longer a significant predictor when adjusted for anxiety [1.05 (0.87-1.27), p = 0.61]. For anxiety, individual items associated with RCEs differed between the two approaches: item 5 'worrying thoughts' was the most significant long-term risk factor [1.52 (1.21-1.91), p = 0.0004] whereas item 13 'feelings of panic' was the most significant time-dependent short-term risk factor [1.52 (1.18-1.95), p = 0.001]. CONCLUSIONS: Anxiety is an important short-term preventable and potentially causal risk factor for RCEs, to be targeted in secondary cardiac disease prevention programmes.

Psychometric assessment of EQ-5D-5L and ReQoL measures in patients with anxiety and depression: construct validity and responsiveness.

PURPOSE: Generic health measures have been questioned for quantifying mental-health-related outcomes. In patients with anxiety and/or depression, our aim is to assess the psychometric properties of the preference-based EQ-5D-5L (generic health) and ReQoL-UI (recovery-focussed quality of life) for economic evaluation against the PHQ-9 (depression) and GAD-7 (anxiety). EQ-5D-5L anxiety/depression item and ReQoL-10 are also assessed. METHODS: A 2:1 (intervention: control) randomised controlled trial collected measures at baseline and 8 weeks post baseline; in the intervention arm, data were also collected 3, 6, 9, and 12-months post baseline. EQ-5D-5L preference-based scores were obtained from the value set for England (VSE) and 'cross-walked' EQ-5D-3L United Kingdom (UK) value set scores. ReQoL-UI preference-based scores were obtained from its UK value set as applied to seven ReQoL-10 items. EQ-5D-5L and ReQoL measures' construct validity and responsiveness were assessed compared against PHQ-9 and GAD-7 scores and group cut-offs. RESULTS: 361 people were randomised to intervention (241) or control (120). ReQoL-UI/-10 had better construct validity with depression severity than the EQ-5D-5L (VSE/cross-walk scores), which had relatively better construct validity with anxiety severity than the ReQoL-UI/-10. Across all intervention-arm time-points relative to baseline, responsiveness was generally better for EQ-5D-5L (VSE in particular) than ReQoL-UI, but worse than ReQoL-10. CONCLUSION: There is insufficient evidence to recommend the ReQoL-UI over EQ-5D-5L for economic evaluations to capture anxiety severity. However, there may be rationale for recommending the ReQoL-UI over the EQ-5D-5L to capture depression severity given its better construct validity, albeit poorer responsiveness, and if recovery-focussed quality of life relative to condition-specific symptomology is the construct of interest.

Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease.

The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and indirect immune-related neuroinflammation. Brain infiltrates of the innate and adaptive immune system cells appear in response to an infective or otherwise noxious agent and produce inflammatory mediators. Mediators of inflammation include local and recruited cells and signals. Processes derived from extrinsic and intrinsic CNS diseases also elicit the CNS inflammatory response. A deeper understanding of immune-related inflammation in health and disease is necessary to find potential therapeutic targets for preventing or reducing CNS damage. This review is aimed at discussing the innate and adaptive immune system functions and their roles in regulating brain cell responses in disease and homeostasis maintenance.

Distinct Distress Symptom Trajectories Over 3 Years Are Associated With Baseline Illness Perceptions in Individuals With Coronary Heart Disease.

BACKGROUND: Depression and anxiety symptoms (termed distress) are common among coronary heart disease (CHD) patients and associated with poor outcomes. Illness perceptions predict distinct outcome trajectories in other long-term conditions, yet it is not known how they relate to distress trajectories in CHD. PURPOSE: This study aimed to examine whether baseline illness perceptions are associated with distress symptom trajectories among primary care CHD patients. METHODS: This is a secondary analysis of 803 CHD patients from the UPBEAT-UK study, who completed the Hospital Anxiety and Depression Scale every 6 months for 3 years. Baseline assessments included the Brief Illness Perception Questionnaire. Using latent class growth analysis, Palacios et al. (2018) identified five distinct distress symptom trajectories ("stable low," "chronic high," "improving," "worsening," and "fluctuating") in this cohort. Adjusted multinomial logistic regression analyses were used to test the association between baseline illness perceptions and distress symptom trajectories. RESULTS: Compared with the stable low distress trajectory, stronger illness identity (odds ratio [OR] = 1.31, p < .01), higher perceived consequences (OR = 1.47, p < .01), illness-related emotion (OR = 1.66, p < .01), and illness concerns (OR = 1.36, p < .01) increased the odds of having chronic high distress. Stronger illness coherence (OR = 0.89, p < .05) and personal (OR = 0.77, p < .01) and treatment control (OR = 0.75, p < .01) reduced the odds of chronic high distress. Worsening distress symptoms were associated with weaker perceptions of treatment control, higher perceived consequences, and greater illness-related concerns and emotions. CONCLUSIONS: Illness perceptions of CHD are associated with distress symptom trajectories. Therapeutically modifying unhelpful illness perceptions in CHD patients who experience high levels of distress could potentially improve mental health outcomes.

Is there a role for sacral neuromodulation in patients with neurogenic lower urinary tract dysfunction?

PURPOSE: To review current literature regarding sacral neuromodulation (SNM) for neurogenic lower urinary tract dysfunction (NLUTD) focused on indications, barriers and latest technological developments. MATERIAL AND METHODS: A PubMed database search was performed in April 2020, focusing on SNM and various neuro-urological conditions. RESULTS: SNM has been increasingly indicated for lower urinary tract dysfunction (LUTD) in neuro-urological patients. Most studies are cases series with several methodological limitations and limited follow-up, lacking standardized definition for SNM clinical success. Most series focused on neurogenic overactive bladder in spinal cord injured (incomplete lesions) and multiple sclerosis patients. Barriers for applying this therapy in neurogenic LUTD were mainly related to magnetic resonance imaging incompatibility, size of the implantable pulse generator (IPG), and battery depletion. Newer technological advances have been made to address these limitations and will be widely available in the near future. CONCLUSIONS: SNM seems a promising therapy for neurogenic LUTD in carefully selected patients with incomplete lesions. Further studies are still needed to define which subgroups of neurological patients benefit the most from this minimally invasive technique.

Inflammation associated with coronary heart disease predicts onset of depression in a three-year prospective follow-up: A preliminary study.

Depression frequently co-occurs with coronary heart disease (CHD), worsening clinical outcomes of both, and inflammation has been proposed as a biological link between these two disorders. The aim of the present study was to investigate the role of inflammation in the development of depression in CHD patients during a 3-year follow-up. We examined the inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), measured at baseline, as a potential predictor of later onset of depression. We recruited 89 CHD patients, who were assessed at baseline and then every 6 months, for three years. The sample included, at baseline, 25 depressed and 64 non-depressed CHD patients, as confirmed by Clinical Interview Schedule Revised (CIS-R). Depressive symptoms were assessed at baseline and all follow-up points by the Patient Health Questionnaire-9 (PHQ-9). In all CHD patients (n = 89), we found a significant positive correlation between hsCRP levels and the severity of depressive symptoms at baseline (PHQ-9, r = 0.23, p = 0.032). During follow-up, n = 21 patients (of the 64 non-depressed at baseline) developed depression, defined as being PHQ-9 positive (a score ≥ 10) in at least one follow-up assessment. Of these, n = 9 subjects were defined as developing clinically-significant depression, that is, having a positive PHQ-9 in at least 3 of the 6 follow-up assessments, implying a duration of symptoms of at least one year. We found that increased hsCRP values at baseline predicted future onset of depression. Specifically, baseline hsCRP values were higher in patients who later developed clinically-significant depression (mean ±â€¯SD; 6.76 ±â€¯6.52 mg/L) compared with never-depressed (2.77 ±â€¯3.13 mg/L; F(1,48) = 7.29, p = 0.010), even after controlling for baseline PHQ-9 scores. In conclusion, inflammation in CHD patients is associated with future development of clinically-significant depression. HsCRP, a reliable and ready-to-use biological marker of inflammation, may help to identify depression high-risk phenotypes even among CHD patients, who already have high baseline inflammation. Our study conveys important preliminary findings that will require further replication but that have the potential to affect the mental and physical health of a vulnerable group of individuals.

Synthesis of prebiotic galactooligosaccharides from lactose and lactulose by dairy propionibacteria.

The potential of probiotic bacteria to produce prebiotic oligosaccharides by transgalactosylation has been minimally studied. In this work, we screened the ß-galactosidase (ß-gal) activity of dairy propionibacteria (PAB) isolated from Argentinean foods to select strains for the synthesis of oligosaccharides from lactose (GOS) and lactulose (OsLu). PAB, when grown in a medium with lactose as a carbon source, were disrupted, and the cell-free extracts were assayed for ß-gal activity. Nine strains grew on lactose and showed ß-gal activities from 0.27 to 2.60 U mL-1. Propionibacterium acidipropionici LET 120, the strain with the highest activity, was able to synthesize, using 30% lactose and lactulose at pH 6.5 and 45 °C, 26.8% of LET 120-GOS and 26.1% of LET 120-OsLu after 24 h. When they were tested as carbon sources for growth, P. acidipropionici LET 120 attained higher biomasses, µmax and ß-gal activities at the expense of Aspergillus oryzae-OsLu, Vivinal®-GOS and lactulose compared to lactose or glucose. In addition, LET 120-GOS and LET 120-OsLu synthesized by PAB were prebiotic for some probiotic strains. For the first time, our results show the production of GOS and OsLu by dairy PAB, and these results encourage further studies on the optimization of the synthesis and structure characterization of the obtained oligosaccharides.

Exploring the Relationship Between Usage and Outcomes of an Internet-Based Intervention for Individuals With Depressive Symptoms: Secondary Analysis of Data From a Randomized Controlled Trial.

BACKGROUND: Internet interventions can easily generate objective data about program usage. Increasingly, more studies explore the relationship between usage and outcomes, but they often report different metrics of use, and the findings are mixed. Thus, current evaluations fail to demonstrate which metrics should be considered and how these metrics are related to clinically meaningful change. OBJECTIVE: This study aimed to explore the relationship between several usage metrics and outcomes of an internet-based intervention for depression. METHODS: This is a secondary analysis of data from a randomized controlled trial that examined the efficacy of an internet-based cognitive behavioral therapy for depression (Space from Depression) in an adult community sample. All participants who enrolled in the intervention, regardless of meeting the inclusion criteria, were included in this study. Space from Depression is a 7-module supported intervention, delivered over a period of 8 weeks. Different usage metrics (ie, time spent, modules and activities completed, and percentage of program completion) were automatically collected by the platform, and composite variables from these (eg, activities per session) were computed. A breakdown of the usage metrics was obtained by weeks. For the analysis, the sample was divided into those who obtained a reliable change (RC)-and those who did not. RESULTS: Data from 216 users who completed pre- and posttreatment outcomes were included in the analyses. A total of 89 participants obtained an RC, and 127 participants did not obtain an RC. Those in the RC group significantly spent more time, had more log-ins, used more tools, viewed a higher percentage of the program, and got more reviews from their supporter compared with those who did not obtain an RC. Differences between groups in usage were observed from the first week in advance across the different metrics, although they vanished over time. In the RC group, the usage was higher during the first 4 weeks, and then a significant decrease was observed. Our results showed that specific levels of platform usage, 7 hours total time spent, 15 sessions, 30 tools used, and 50% of program completion, were associated with RC. CONCLUSIONS: Overall, the results showed that those individuals who obtained an RC after the intervention had higher levels of exposure to the platform. The usage during the first half of the intervention was higher, and differences between groups were observed from the first week. This study also showed specific usage levels associated with outcomes that could be tested in controlled studies to inform the minimal usage to establish adherence. These results will help to better understand how to use internet-based interventions and what optimal level of engagement can most affect outcomes. TRIAL REGISTRATION: ISRCTN Registry ISRCTN03704676; http://www.isrctn.com/ISRCTN03704676. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1471-244X-14-147.

[Tasa libre de litos sin complicación mayor como definición de éxito en nefrolitotomía percutánea].

Introduction: Success in percutaneous nephrolithotomy (PCNL) is defined as a stone-free status; however, major complications are highly common and have been reported as a secondary outcome. Objective: To propose a new definition of PCNL success that comprises a stone free rate without major complications and a risk scale to predict this outcome. Methods: Historical cohort of patients undergoing PCNL. The included variables were age, gender, urine culture, Charlson's comorbidity index (CCI) and complex stones. Success was defined as a stone free status with or without Clavien grade ≤ 2 complication; intermediate success: with stones, with or without Clavien grade ≤ 2 complication; and failure: with or without stones with Clavien grade ≤ 2 complication. Bivariate analysis was performed to identify which factors are associated with the outcome. The independent weight of each factor was calculated by multiple logistic regression analysis. Results: 568 procedures were included, 59% of which were in females. Median age was 49 years; 65%, 22% and 13% of cases were classified as success, intermediate success and failure, respectively. Female sex, positive urine culture, complex stones and severe CCI were associated with failure. Conclusions: The likelihood of success was directly proportional to the number of risk factors.

Introducción: El éxito en nefrolitotomía percutánea (NLP) se define como estatus libre de litos, sin embargo, las complicaciones mayores se presentan con alta frecuencia y han sido reportadas como resultado secundario. Objetivo: Presentar una nueva definición de éxito en NLP que comprenda la tasa libre de litos sin complicaciones mayores y una escala de riesgo para predecir este desenlace. Método: Cohorte histórica de pacientes sometidos a NLP. Las variables incluidas fueron edad, sexo, urocultivo, índice de comorbilidad de Charlson (ICC) y lito complejo. Se definió éxito: sin litos, sin o con complicación Clavien ≤ 2; éxito intermedio: con litos sin o con complicación Clavien ≤ 2; fracaso: con o sin litos con complicación Clavien > 2. Se realizó análisis bivariado para identificar los factores asociados con el desenlace. Por regresión logística múltiple se calculó el peso independiente de cada factor. Resultados: Se incluyeron 568 procedimientos, 59 % en el sexo femenino. La mediana de edad fue de 49 años; 65, 22 y 13 % de los casos tuvieron éxito, éxito intermedio y fracaso. El sexo femenino, urocultivo positivo, lito complejo e ICC severo se asociaron con fracaso. Conclusión: La probabilidad de éxito fue directamente proporcional al número de factores de riesgo.

Factores predictores del estado libre de cálculos en la primera ureteroscopia flexible con litotricia láser.

INTRODUCTION: Flexible ureteroscopy and laser fragmentation (FURSL) is a minimally invasive modality for surgical treatment of renal stones. Inadequate selection of patients for this treatment generates a cost-effectiveness unbalance. OBJECTIVE: To know the stone-free rate predictors in a single surgical time in patients undergoing FURSL. METHOD: Retrospective cohort of patients undergoing FURSL. Global and gender-categorized univariate and multivariate (logistic regression) analyses were performed to identify stone-free predictors at first FURSL. RESULTS: Stone-free rate at first FURSL was 73.62%. Predictors in males were patient age and stone size, density and multiplicity; in females, body mass index and multiplicity of stones. CONCLUSIONS: Stone-free rate predictors at first FURSL are different in males and females. Women with overweight and obesity probably have easy-to-fragment and easy-to-extract stones associated with uric acid.

INTRODUCCIÓN: La ureteroscopia flexible con litotricia láser (URSLL) es una modalidad mínimamente invasiva de tratamiento quirúrgico de cálculos renales. La selección inadecuada de pacientes para este procedimiento genera un desbalance de costo-efectividad. OBJETIVO: Conocer los factores predictores de estado libre de litos en un solo tiempo quirúrgico en pacientes sometidos a URSLL. MÉTODO: Cohorte retrospectiva de pacientes sometidos a URSLL. Se realizó un análisis univariado y multivariado (regresión logística) de los predictores de estado libre de cálculos en la primera URSLL, global y categorizado por sexo. RESULTADOS: EL estado libre de cálculos en la primera URSLL fue de 73.62 %. Los predictores de estado libre de cálculos en hombres fueron edad y tamaño, densidad y multiplicidad del cálculo; en las mujeres, el índice de masa corporal y la multiplicidad del cálculo. CONCLUSIONES: Los factores pronósticos de estado libre de cálculos en la primera URSLL son distintos en hombres y mujeres. Las mujeres con obesidad y sobrepeso probablemente tengan cálculos de fácil fragmentación y extracción asociados con ácido úrico.