Sugar-Sweetened Beverages and Adverse Human Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies.

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health.

Determinants of depression among undergraduate medical students of a private medical college in Lahore.

OBJECTIVE: To assess the prevalence and determinants of depression in undergraduate medical students within their learning environment. METHODS: The descriptive cross-sectional study was conducted at the Lahore Medical and Dental College, Lahore, Pakistan, from May to June 2015, and comprised medical students of all the five professional years. A structured questionnaire was used to collect data. Section one of the questionnaire related to demographic information, section two comprised Patient health questionnaire-9 for screening depression, and section three was the Dundee ready education environment measure inventory to gather students' perceptions of their learning environment. Data was analysed using SPSS 22. RESULTS: Of the 533 students, 206(39%) were males, 327(61%) were females, 213(40%) were of preclinical years and 320(60%) were of clinical academic years. Overall, 399(75%) students were found to be depressed. Of them, 255(64%) were females and 144(36%) were males. Among the students, 96(18%) had negative perception of their learning environment, and out of these, 91(95%) were found to be depressed. There was significant association of depression with female gender (p=0.037) and negative perception of the students of their learning climate (p<0.001). CONCLUSIONS: The prevalence of depression was found to be high among the medical students and it was associated with female gender and negative perception of the learning environment.

High paternal testosterone may protect against postpartum depressive symptoms in fathers, but confer risk to mothers and children.

Following the birth of an infant, decreases in testosterone and increases in depressive symptoms have been observed in fathers. Paternal testosterone may reflect fathers' investment in pair-bonding and paternal caregiving and, as such, may be associated with maternal and familial well-being. This study tests associations between paternal testosterone, paternal and maternal postpartum depressive symptoms, and subsequent family functioning. Within 149 couples, fathers provided testosterone samples when infants were approximately nine months old and both parents reported on postpartum depressive symptoms at two, nine, and 15months postpartum. Fathers with lower aggregate testosterone reported more depressive symptoms at two and nine months postpartum. Mothers whose partners had higher evening testosterone reported more depressive symptoms at nine and 15months postpartum. Maternal relationship satisfaction mediated this effect, such that mothers with higher testosterone partners reported more relationship dissatisfaction, which in turn predicted more maternal depressive symptoms. Higher paternal testosterone and paternal depressive symptoms at nine months postpartum each independently predicted greater fathering stress at 15months postpartum. Higher paternal testosterone also predicted more mother-reported intimate partner aggression at 15months postpartum. In addition to linear relationships between testosterone and depression, curvilinear relationships emerged such that fathers with both low and high testosterone at nine months postpartum reported more subsequent (15-month) depressive symptoms and fathering stress. In conclusion, whereas higher paternal testosterone may protect against paternal depression, it contributed to maternal distress and suboptimal family outcomes in our sample. Interventions that supplement or alter men's testosterone may have unintended consequences for family well-being.

Aerobic and resistance training improves mood state among adults living with HIV.

The purpose of this investigation was to examine the effects of combined aerobic and resistance exercise training among self-reported mood disturbances, perceived stress, frequency of self-reported symptoms, and symptom distress in a sample of HIV+ adults. For this purpose, 49 participants were randomly assigned into an exercise (EX) or control (CON) group. Those in the EX group completed 50 min of supervised aerobic and resistance training at a moderate intensity twice a week for 6 weeks. The CON group reported to the university and engaged in sedentary activities. Data were collected at baseline before randomization and 6 weeks post intervention. Measures included the symptom distress scale (SDS), perceived stress scale (PSS), profile of mood states (POMS) total score, and the POMS sub-scale for depression and fatigue. A 2 way ANOVA was used to compare between and within group interactions. The EX group showed a significant decrease in reported depression scores (p=0.03) and total POMS (p=0.003). The CON group reported no change in POMS or SDS, but showed a significant increase in PSS. These findings indicate that combination aerobic and resistance training completed at a moderate intensity at least twice a week provides additional psychological benefits independent of disease status and related symptoms.

Citalopram for the prevention of depression and its consequences in HIV-hepatitis C coinfected individuals initiating pegylated interferon/ribavirin therapy: a multicenter randomized double-blind placebo-controlled trial.

BACKGROUND: Depression related to interferon-alpha (IFN-α) is common, may reduce adherence, and can be treatment limiting. HIV-HCV coinfected persons experience lower sustained virologic response rates and commonly have psychiatric comorbidities, thus they may benefit from prevention of depression. OBJECTIVE: The aim of the study was to determine whether prophylactic citalopram can increase HCV treatment adherence and reduce the incidence of moderate depression in HIV-HCV coinfected patients initiating PEG-IFN-α/ribavirin therapy. METHODS: This was an investigator-initiated Canadian multicenter randomized, double-blind placebo-controlled trial. HIV-HCV coinfected patients were randomized in a 1:1 ratio to receive citalopram or placebo 3 weeks prior to starting PEG-IFN-α2b/ribavirin, stratified by study center and HCV genotype. The protocol design permitted the comparison of prophylaxis with the treatment of emergent depression. The primary outcomes were adherence (assessed through questionnaire and returned medication) and time to moderate depression measured by Beck Depression Inventory-II (BDI- II) score greater than 15, confirmed 2 weeks apart. RESULTS: Seventy-six patients (36 citalopram/40 placebo) were randomized. Overall adherence was high, ranging from 95% (week 12) to 91% (week 48). There was no difference between arms with respect to mean or median adherence at any study time point. Cumulative incidence of moderate depression did not differ significantly by group (log rank P = .32). The hazard ratio for moderate depression was 0.81 (95% CI, 0.26 to 2.54) for citalopram compared with placebo when adjusted for baseline BDI-II score. CONCLUSIONS: A strategy of prophylactic citalopram compared to treatment of emergent depression was not associated with higher adherence or a reduction in treatment-limiting depression nor did it significantly reduce depressive symptoms among HIV-HCV coinfected persons during treatment for HCV.

Measures against preschool noise and its adverse effects on the personnel: an intervention study.

PURPOSE: The aim of the study was to analyze the exposure effects of different types of noise measures carried out at preschools. The project was carried out as an intervention study. METHODS: The investigation included 89 employees at 17 preschools in the northern part of Sweden. Individual noise recordings and recordings in dining rooms and play halls were made at two departments in each preschool. The adverse effects on the employees were analyzed with validated questionnaires and saliva cortisol samples. Evaluations were made before and 1 year after the first measurement. Between the two measurements, measures were taken to improve the sound environments at the preschools. RESULTS: The effects of the measures varied a lot, with respect to both the sound environments and health. Regarding acoustical measures, significant changes were seen for some of the variables analyzed. For most of the tested effects, the changes, however, were very small and non-significant. The effects of organizational measures on the objective and subjective noise values were in overall less pronounced. CONCLUSION: Acoustical measures improved the subjectively rated sound environment more than organizational measures. This may be due to the high work effort needed to implement organizational measures. Even though the sound level was not lower, the personnel experienced improvements of the sound environment.

Depressive symptoms, low-grade inflammation, and poor oral health prevents the success of nutritional guidance in older caregivers.

PURPOSE: The present study aimed to determine which factors prevents the success of nutritional interventions for older family caregivers (FCs), in the form of individually tailored nutritional guidance. METHODS: The present study focuses on the intervention group of FCs (n = 63) of a randomized controlled trial. Older FCs (≥60 years of age) receiving a care allowance for a home-living care recipient (≥65 years of age) were included in the present study, which focused on nutritional interventions via individually tailored nutritional guidance provided by a clinical nutritionist. The associations between changes in protein intake (3-day food record), Mini Nutritional Assessment (MNA) scores, and plasma albumin and prealbumin concentrations, as well as associated factors, for the 6-month intervention period were analyzed using generalized estimating equations. RESULTS: Intervention time, female sex, older age, higher net income, better hand grip strength, more teeth, and removable denture use were positively associated with an increase in protein intake. Fewer depressive symptoms were associated with a positive change in the MNA scores. Younger age, lower education level, lower body mass index (BMI), higher depressive symptoms, and fewer teeth were associated with an increase in plasma albumin concentration. Younger age, lower education, lower plasma concentration of high-sensitivity C-reactive protein at 6 months, lower Sense of Coherence (SOC) -13 score, fewer teeth, and absence of removable dentures were associated with an increase in plasma prealbumin concentration. CONCLUSION: Older female FCs with a higher income, better hand grip strength, lower education, and lower SOC benefited most from individually tailored nutritional guidance. Depressive symptoms, oral health, and low-grade inflammation should be considered when providing nutritional guidance to older FCs. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04003493 (July 1, 2019).

Improvement in physiological and psychological parameters after 6 months of yoga practice.

Yoga is believed to have beneficial effects on cognition, attenuation of emotional intensity and stress reduction. Previous studies were mainly performed on eastern experienced practitioners or unhealthy subjects undergoing concomitant conventional therapies. Further investigation is needed on the effects of yoga per se, as well as its possible preventive benefits on healthy subjects. We investigated the effects of yoga on memory and psychophysiological parameters related to stress, comparing yoga practice and conventional physical exercises in healthy men (previously yoga-naïve). Memory tests, salivary cortisol levels and stress, anxiety, and depression inventories were assessed before and after 6 months of practice. Yoga practitioners showed improvement of the memory performance, as well as improvements in psychophysiological parameters. The present results suggest that regular yoga practice can improve aspects of cognition and quality of life for healthy individuals. An indirect influence of emotional state on cognitive improvement promoted by yoga practice can be proposed.

Developing effective animal-assisted intervention programs involving visiting dogs for institutionalized geriatric patients: a pilot study.

AIM: An ever increasing interest in the therapeutic aspects of the human-animal bond has led to a proliferation of animal-assisted interventions (AAI) involving dogs. However, most of these programs lack a solid methodological structure, and basic evaluative research is needed. The purpose of this study was to test the value of dog-assisted interventions as an innovative tool to increase quality of life in the geriatric population. METHODS: Nineteen patients (men and women) with a mean age of 85 years participated in the study. Interactions between patients and visiting dogs occurred either in a social situation (socialization sessions) or in a therapeutic context (physical therapy sessions). We derived and characterized a specific ethogram of elderly-dog interactions aimed at evaluating the effectiveness of visiting dogs in improving mood, catalyzing social interactions and reducing their everyday apathetic state. Cortisol levels were also measured in the saliva, and depressive state was evaluated. RESULTS: Overall, results show a time-dependent increase in social behaviour and spontaneous interactions with the dogs. Dog-mediated interactions affected the daily increase in cortisol levels, thus having an 'activational effect', in contrast to the apathetic state of institutionalized elderly. CONCLUSIONS: Dog-mediated intervention programs appear to be promising tools to improve the social skills and enrich the daily activities of the institutionalized elderly.

Significant immediate and long-term improvement in quality of life and disease coping in patients with vitiligo after group climatotherapy at the Dead Sea.

Quality of life in patients with vitiligo is impaired. This study explored the immediate effect of 20 days of climatotherapy at the Dead Sea on quality of life, coping with the disease, general well-being and individual stress levels in a group of 71 patients with vitiligo and 42 matched controls. The long-term effect was assessed after 12 months in 33/71 patients and 12/42 controls. Study instruments were Dermatology Life Quality Index, Beck Depression Inventory and the Adjustment to Chronic Skin Disorders Questionnaire. Stress measurements were based on cortisol and ß-endorphin concentrations in saliva samples. Quality of life was significantly improved at day 20 at the Dead Sea compared with day 1, and this was still significant after 12 months. Moreover, social anxiety/avoidance, anxious-depressive mood and helplessness as measured by the Adjustment to Chronic Skin Disorders Questionnaire were significantly reduced. There was no difference in levels of cortisol and ß-endorphin between patients and controls, indicating that stress per se is not a significant contributor in vitiligo. In conclusion, therapy in patient groups offers an effective tool for long-lasting improvement in quality of life and patients' well-being.

Long-term efficacy of resilient appliance therapy in TMD pain patients: a randomised, controlled trial.

The aim was to investigate long-term efficacy of a resilient appliance in patients with pain due to temporomandibular disorders (TMD). A randomised, controlled trial was performed in 80 recruited TMD pain patients. They were randomly allocated to one of two groups: treatment with a resilient appliance or treatment with a hard, palatal, non-occluding appliance. The primary treatment outcome was judged positive when patients' characteristic pain intensity decreased by at least 30%. Additional treatment outcomes were physical functioning, emotional functioning and headache. At the 12-month follow-up 50% of the patients in the treatment group and 42% in the control group had a 30% reduction of characteristic pain intensity, when calculated in an intent-to-treat analysis. Jaw function improved in both groups at the 6- and 12-month follow-up. Emotional functioning improved in both groups at the 6-month follow-up; an improvement concerning grade of depression was found in the control group at 12 months. Headache decreased in both groups at both follow-ups. There were no statistically significant differences found regarding primary and additional outcomes between groups at the 6- and 12-months follow-up. There was no statistically significant difference between the resilient appliance and the non-occluding control appliance in reducing TMD pain, physical functioning, emotional functioning and headache in a 12 months perspective.

The Beneficial Role of Filipendula ulmaria Extract in Prevention of Prodepressant Effect and Cognitive Impairment Induced by Nanoparticles of Calcium Phosphates in Rats.

Mineral components of dental composites are used in many medical and dental applications, including preventive, restorative, and regenerative dentistry. To evaluate the behavioural alterations induced by nanosized particles of novel dental composites, by means of depressive level and cognitive functions, experimental groups of rats were chronically administered with nanosized hydroxyapatite (HA), tricalcium phosphate (TCP), and amorphous calcium phosphate (ACP) with or without simultaneous application of Filipendula ulmaria L. (FU) methanolic extract. The significant prodepressant action was observed in groups solely treated with HA and ACP. Besides, prolonged treatment with ACP also resulted in a significant decline in cognitive functions estimated in the novel object recognition test. The adverse impact of calcium phosphates on estimated behavioural functions was accompanied by increased oxidative damage and apoptotic markers in the prefrontal cortex, as well as diminished specific neurotrophin (BDNF) and gabaergic expression. The results of our investigation showed that simultaneous antioxidant supplementation with FU extract prevented calcium phosphate-induced behavioural disturbances, as well as prooxidative and apoptotic actions, with the simultaneous restoration of BDNF and GABA-A receptors in the prefrontal cortex. These findings suggest that FU may be useful in the prevention of prodepressant impact and cognitive decline as early as the manifestation of calcium phosphate-induced neurotoxicity.

A multidisciplinary therapeutic approach for reducing the risk of psychiatric side effects in patients with chronic hepatitis C treated with pegylated interferon α and ribavirin.

GOALS: To evaluate the effectiveness of psychiatric counseling in reducing the rate of development of psychiatric side effects of antiviral therapy with interferon-α and ribavirin among study participants compared with standard clinical monitoring alone. BACKGROUND: Interferon-α is used to treat chronic hepatitis C. Interferons may induce adverse events that usually, but not always, reverse within a few days after the end of therapy. STUDY: Two hundred eleven patients with chronic hepatitis C, genotype 1b were treated with peginterferon and ribavirin for 48 weeks in a prospective trial. Two groups were randomly created. Group A was interviewed by a team of gastroenterologists, psychiatrists, and psychologists and treated with psychotherapy once a month. Group B was monitored once a month according to a conventional protocol that did not include psychotherapy. SVR (sustained viral response), severe psychiatric symptom onset, and mood progression were assessed (P calculated using Fisher exact test, Friedman test, Dunn posttest, and Mann-Whitney U-test). RESULTS: At baseline, there was no difference in depressive symptoms or liver histologic score between the 2 groups. The onset rate of severe psychiatric manifestations was 4.7% (Group A) and 16.1% (Group B) between the 24th and 36th weeks (P<0.01). Fifteen participants in Group A and 39 in Group B required antidepressants and benzodiazepines (P<0.05). CONCLUSIONS: Patients can develop depressive symptoms during interferon therapy. Multidisciplinary medical treatment with psychiatric counseling provided during the treatment of chronic hepatitis C may contribute to the decrease or prevent the higher rates of depression associated with interferon treatment.

Effect of occlusal splint on oxidative stress markers and psychological aspects of chronic temporomandibular pain: a randomized controlled trial.

Temporomandibular disorders (TMD), when progress to a chronic state, might contribute to psychosocial or psychological distress. This study aimed to evaluate the effect of stabilization splint (SS) therapy on pain, pain-related disability and psychological traits of chronic TMD patients, as well as to assess selected oxidative stress (OS) biomarkers during 6-month treatment and associate them with the symptoms of anxiety and depression. Thirty-four participants were randomly assigned into two treatment groups [SS and placebo splint (PS)]. Primary outcomes were pain intensity and pain-related disability while secondary outcomes included depressive and anxiety symptoms. The influence of the treatment type was analyzed with regards to the levels of OS biomarkers in saliva. Participants treated with SS demonstrated significantly greater improvement in pain-related disability (Pain-free mouth opening: p = 0.018, η2 = 0.166; Number of disability days: p = 0.023, η2 = 0.155) and greater reduction of depressive symptoms scores (p = 0.007, η2 = 0.207). When compared to the PS group, participants in the SS group showed a significant reduction of oxidant/antioxidant ratio (p = 0.018, η2 = 0.167) at a 3-month follow-up. A stabilization splint provides advantages over PS in the treatment of depressive symptoms and pain-related disability. Furthermore, clinical success in terms of reduction of depressive symptoms, which correlates with the reduction of oxidative stress markers in the SS group, indicates that oxidative stress is related to psychological factors in chronic TMD patients.

Lower prevalence of depression in hemodialysis patients who use polysulfone dialyzers.

BACKGROUND: Depression is common in dialysis patients and is also associated with the presence of chronic inflammation. Dialysis patients who use polysulfone dialyzers are less likely to have inflammation. It is unknown whether the use of polysulfone dialyzers is associated with lower prevalence of depression. METHOD: The aim of this cross-sectional study is to examine the association between the use of polysulfone dialyzers and depression in dialysis patients. This association was examined by use of univariate and multivariate analysis. RESULTS: Depression affected 35% of our hemodialysis patients. Compared with nondepressed patients, depressed patients were more likely to be male, thinner (lower body mass index), and have more comorbidities. Depression was also associated with the use of cellulose derivative dialyzers (p = 0.008). In multivariate analysis with stepwise regression, gender, albumin, number of comorbidities, and BMI lost their significance. However, the use of polysulfone dialyzers remained correlated with a lower prevalence of depression (odds ratio 0.063, 95% confidence interval 0.01-0.43; p = 0.005). This indicates that the type of dialyzer is independently associated with depression in these hemodialysis patients. CONCLUSION: The prevalence of depression was lower in patients using polysulfone dialyzers than cellulose derivative dialyzers. Using more biocompatible dialyzers appears to be associated with better mental health in hemodialysis patients.

Effects of low-power laser auriculotherapy on the physical and emotional aspects in patients with temporomandibular disorders: A blind, randomized, controlled clinical trial.

OBJECTIVES: This study evaluated the effects of low-power laser auriculotherapy (LA) on the physical and emotional symptoms of patients with temporomandibular disorders (TMDs), in comparison with occlusal splints (OS). DESIGN: Randomized, blinded, prospective, non-inferiority clinical trial. INTERVENTIONS: The patients received OS (control group) or LA (experimental group). MAIN OUTCOME MEASURES: Following the Consolidated Standards of Reporting Trials (CONSORT) guidelines, patients with TMD were evaluated by using axes I and II of the Research Diagnostic Criteria for RDC-TMD. Both intra- and intergroup quantitative variables were analyzed with ANOVA (p < 0.05), while qualitative variables were analyzed with the Kruskal-Wallis (intergroup evaluations; p < 0.05) or Mann-Whitney tests (intragroup analyses; p < 0.05). RESULTS: OS improved five physical symptoms of TMD (pain in the right temporal muscle, right and left masseter muscles, left joint, and left intraoral region), while LA improved six (jaw functioning; pain in left masseter muscle, right and left joints, and right and left intraoral regions). Similarly, OS improved seven emotional symptoms (degree of depression, degree of non-specific physical symptoms, excluding pain, degree of non-specific physical symptoms including pain, average pain value in the past 6 months, presence of depression, intensity and characteristics of pain, non-specific physical symptoms including pain), while LA improved five (degree of non-specific physical symptoms including pain, presence of depression, intensity and characteristics of pain, non-specific physical symptoms including pain, non-specific physical symptoms excluding pain). CONCLUSION: LA improved the physical and emotional symptoms of TMD, with results similar to OS. CLINICAL RELEVANCE: For the physical and emotional symptoms associated with TMD, LA showed similar outcomes as OS.

Management of reticular oral lichen planus patients with burning mouth syndrome-like oral symptoms: a pilot study.

OBJECTIVES: We sought to determine the efficacy of psychotropic drug in the management of BMS-like oral symptoms in patients with reticular oral lichen planus (R-OLP) refractory to conventional therapies, and its impact on anxious and depressive symptoms. MATERIALS AND METHODS: We enrolled 28 cases of symptomatic R-OLP. The Numeric Rating Scale (NRS), the Total Pain Rating Index (T-PRI), the Hamilton rating scales for Depression (HAM-D) and Anxiety (HAM-A) were performed at baseline (time 0), after 2 months of topical clonazepam (time 1) and after 6 months of benzodiazepine and antidepressant drugs (time 2). RESULTS: R-OLP patients showed a statistically significant improvement in the NRS and T-PRI scores from time 0 [median: 9.0 (IQR: 7.2-10.0) and 10.5 (IQR: 7.0-13.0), respectively] to time 2 [(median: 2.0 (IQR: 2.0-3.0) (p < .001) and 3.0 (IQR: 2.0-4.7) (p < .001), respectively]. Similarly, the HAM-A and HAM-D scores showed an improvement from time 0 [(median: 15.0 (IQR: 10.2-17.8) and 13.0 (IQR: 12.0-15.0), respectively] to time 2 [median: 6.0 (IQR: 4.0-7.0) (p < .001) and 5.5 (IQR: 4.25-6.0) (p < .001), respectively]. CONCLUSIONS: Psychotropic drugs turned out to be effective in the management of BMS-like oral symptoms in R-OLP patients refractory to conventional immunosuppressive therapy, although in a long-term period.

Comparative effectiveness of photobiomodulation and manual therapy alone or combined in TMD patients: a randomized clinical trial.

The effectiveness of photobiomodulation (PBM) and manual therapy (MT), alone or combined (CT), were evaluated in pain intensity, mandibular movements, psychosocial aspects, and anxiety symptoms of temporomandibular disorder (TMD) patients. Fifty-one TMD patients were randomly assigned to three groups: the PBM group (n = 18), which received PBM with 808 nm, 100 mW, 13.3 J/cm2, and 4 J per point; the MT group (n=16) for 21 minutes each session on masticatory muscles and temporomandibular joint TMJ; and the CT group (n = 17), applied during twelve sessions. Seven evaluations were performed in different moments using visual analogue scale (VAS), Research Diagnosis Criteria for Temporomandibular Disorders (RDC/TMD) Axis I and II, and Beck anxiety inventory (BAI). All groups demonstrated reductions in pain and improvement in jaw movements during treatment and at follow-up (< 0.001). The assessment of psychosocial aspects of TMD, comparing baseline and follow-up in all treatment groups, revealed that treatment did not promote modification in the intensity of chronic pain (p > 0.05). However, depression symptoms showed a reduction in PBM and CT groups (p≤0.05). All treatments promoted reduction in physical symptoms with and without pain and enhancement of jaw disabilities (p ≤ 0.05). MT promotes improvement in 5 functions, PBM in 2, and CT in 1 (p < 0.001). BAI analysis revealed that all treatments lead to a reduction in anxiety symptoms (p≤0.05). All protocols tested were able to promote pain relief, improve mandibular function, and reduce the negative psychosocial aspects and levels of anxiety in TMD patients. However, the combination of PBM and MT did not promote an increase in the effectiveness of both therapies alone.