Mind it! A mindfulness-based group psychotherapy for substance use disorders in adolescent inpatients.

Cannabis use disorder (CUD) is the most frequent reason for psychiatric inpatient substance use disorder (SUD) treatment among 15-19-year-olds in Germany. Despite effective treatment programs, relapse rates remain high. Thus, existing multi-component programs (TAU) need to be enhanced with SUD-specific elements. Mindfulness-based interventions (MBI) seem promising as they can positively influence SUD-related behaviors (e. g. craving). Given limited research in adolescents, this randomized controlled trial investigated the extent to which MBI-based group therapy (Mind it!) as an add-on treatment to TAU led to fewer cannabis use days after 6 months in 84 adolescent inpatients with CUD. Additionally, craving, severity of CUD, and changes in mindfulness were monitored (pre-, post-, and follow-up (FU) assessments). The results revealed a significant reduction in cannabis use days in both groups at 6-month FU (d = - 0.72 and = - 0.75). Although minor additional benefits of Mind it! were evident post-treatment, specifically reduction of craving and SUD severity, by the 6-month mark, TAU exhibited a more substantial decrease in SUD severity (d = 0.78), and reward craving (d = 0.28) compared to Mind it!. Regarding self-regulation skills (mindfulness), Mind it! demonstrated superiority over TAU after 6-month FU (d = 0.27). Therapists judged the MBI as feasible. (Serious) adverse events were unrelated to Mind it!. There was a systematic dropout among Mind it! participants. Primarily, the results emphasize the effectiveness of TAU in reducing cannabis use. MBI also seem feasible for youth, but results remain inconsistent and unstable over time. Importantly, enhanced adherence to reduce dropouts is needed.Trial registration: German Clinical Trials Register, DRKS00014041. Registered on 17 April 2018.

Bright Light Therapy as Add-On to Inpatient Treatment in Youth With Moderate to Severe Depression: A Randomized Clinical Trial.

Importance: Major depressive disorder is one of the most common mental disorders among adolescents, entailing severe, long-term psychosocial impairment and a high risk of chronicity. In view of the large number of patients requiring treatment, along with insufficient treatment responses with small effect sizes, innovative adjunctive treatment strategies are urgently needed. Objective: To investigate whether the effect of adolescent psychiatric inpatient treatment as usual for major depressive disorder can be enhanced by simultaneous use of morning bright light therapy. Design, Setting, and Participants: This was a double-blind, placebo-controlled randomized parallel-group trial with enrollment between March 2018 and November 2020 and follow-up completed in May 2021. The study took place among inpatients at 4 university hospitals for child and adolescent psychiatry across Germany. Of 248 eligible youth aged 12 to 18 years fulfilling ICD-10 criteria for major depressive disorder, 227 were randomized to bright light therapy (n = 116) or placebo red light (n = 111); 151 participants completed the study. Interventions: Up to 20 sessions of either morning bright light therapy with an intensity of 10 000 lux or placebo red light (100 lux) in addition to multimodal inpatient treatment as usual over 4 weeks. Main Outcomes and Measures: The primary outcome was the change in Beck Depression Inventory-II (BDI-II) score from baseline to posttreatment in the intention-to-treat sample. Results: Among the 224 patients included in the intention-to-treat analyses (192 girls and 32 boys; mean [SD] age, 15.5 [1.4] years), the mean (SD) BDI-II score at baseline was 37.3 (8.7). BDI-II scores were significantly reduced after 4 weeks (postassessment) by a mean of -7.5 (95% CI, -9.0 to -6.0; Hedges g = 0.71). Bright light therapy had no impact on this change (no significant group × time effect). Loss to follow-up was 31% (n = 69) at 16 weeks and 49% (n = 110) at 28 weeks. There were 10 serious adverse events throughout the whole trial, which were not considered related to study treatment. Conclusions and Relevance: The findings in this study did not indicate superiority of bright light therapy over placebo red light therapy in a large sample of adolescent inpatients with moderate or severe major depressive disorder. Both groups benefited equally from treatment as usual, showing relevant symptom reduction. Trial Registration: German Clinical Trials Register: DRKS00013188.

[Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria]. / Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie.

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.

Hostile and threatening interpretation biases in adolescent inpatients are specific to callous-unemotional traits and social anxiety.

Psychopathological syndromes, such as disruptive behavior and anxiety disorders in adolescence, are characterized by distorted cognitions and problematic behavior. Biased interpretations of ambiguous social situations can elicit both aggressive and avoidance behavior. Yet, it is not well understood whether different interpretation biases are specific to different syndromes, or whether they can co-occur. We assessed both hostile and threatening interpretation biases in identical social situations, and proposed that they are uniquely related to callous-unemotional (CU) traits and social anxiety, respectively. We also explored the role of gender and age herein. The sample consisted of 390 inpatients between 10 and 18 years of age with a variety of psychiatric disorders. Hostile and threatening interpretations were assessed with the Ambiguous Social Scenario Task (ASST) consisting of 10 written vignettes. Both CU-traits and social anxiety were assessed with self-report questionnaires. Results showed that, overall, CU-traits were related to more hostile interpretations, whereas social anxiety was related to more threatening interpretations. In addition, in boys, hostile and threatening interpretations correlated significantly positive with each other. Age was not related to interpretation biases. Together, these results generally support the content-specificity of interpretation biases in concepts relevant to disruptive behavior disorders and anxiety disorders, and indicate that different interpretation biases can co-occur specifically in boys.

[Interinstitutional cooperation between youth welfare services, child and adolescent psychiatry and adult psychiatry - an empirical study]. / Interinstitutionelle Kooperation der Jugendhilfe, der Kinder- und Jugendlichenpsychiatrie und der Erwachsenenpsychiatrie ­ Eine empirische Untersuchung.

Family support in Germany is provided by a conglomerate of different support systems. In order to optimize the networking and cooperation of these inter-institutional support systems, it is important to gain a deeper understanding of the existing cooperation structures. Against this background, different qualitative and quantitative aspects were surveyed and analyzed by means of a questionnaire among participants from different help systems. The results point in particular to the currently existing special role of adult psychiatry.

The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG).

ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.

The importance of familial risk factors in children with ADHD: direct and indirect effects of family adversity, parental psychopathology and parenting practices on externalizing symptoms.

BACKGROUND: Children experiencing unfavorable family circumstances have an increased risk of developing externalizing symptoms. The present study examines the direct, indirect and total effects of family adversity, parental psychopathology, and positive and negative parenting practices on symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children with ADHD. METHODS: Data from 555 children (M = 8.9 years old, 80.5% boys) who participated in a multicenter study on the treatment of ADHD (ESCAschool) were analyzed using structural equation modeling (SEM). RESULTS: The SEM analyses revealed that (a) family adversity and parental psychopathology are associated with both child ADHD and ODD symptoms while negative parenting practices are only related to child ODD symptoms; (b) family adversity is only indirectly associated with child ADHD and ODD symptoms, via parental psychopathology and negative parenting practices; (c) the detrimental effect of negative parenting practices on child ADHD and ODD symptoms is stronger in girls than in boys (multi-sample SEM); (d) there are no significant associations between positive parenting practices and child ADHD or ODD symptoms. CONCLUSIONS: Family adversity, parental psychopathology, and negative parenting practices should be routinely assessed by clinicians and considered in treatment planning. Trial registration (18th December 2015): German Clinical Trials Register (DRKS) DRKS00008973.

Associations of sleep and emotion regulation processes in childhood and adolescence - a systematic review, report of methodological challenges and future directions.

Sleep and emotions are closely associated; however, the methodological challenges in the examination of sleep and the processes of emotion regulation in children and adolescents have not been investigated so far. Additionally, there is the demand to identify the levels of emotion regulating processes in which problematic or restricted sleep causes effect. Experimental sleep deprivation as well as prevalent sleep problems have been found to have negative influence on mental health and regulating functions. This review focuses first on the methodological protocols of the included studies. Subsequently, the results are summarized in the context of a multilevel model of emotion regulation. Thereafter, suggestions for future directions are given. Sleep problems and sleep deprivation are associated with a decrease of functional emotion regulating behavior and impaired emotion generation, and prolonged sleep enhances better mood and affect states, positive emotion expression, and faster sensory processing in response to emotional stimuli. This literature review highlights the limitations in current research, focusing on types of measurements, task characteristics, and data analysis. At the conclusion, suggestions are given for the future research direction in the field of sleep and emotion regulation in children and adolescents.

Better safe than sorry: Divergent error-related negativity and error positivity in shame-prone adolescents.

BACKGROUND: The present study examines whether adolescents who are prone to shame show intense performance monitoring in order to avoid mistakes. Higher amplitudes of error-related negativity (ERN) or error positivity (Pe) are potential proxies to measure performance monitoring from a neurophysiological perspective. Depressive symptom severity has been found to correlate with increased ERN and Pe amplitudes. However, research on the influence of shame proneness on this correlation is lacking, although it is known that depression comes with greater shame proneness. METHODS: A total of 112 adolescent participants (61 inpatients with a clinical diagnosis of depression and 51 healthy volunteers) performed two rounds of the Eriksen flanker task. In one round, incorrect responses led to derogatory feedback, in the other round, correct responses led to encouraging feedback. ERN and Pe after incorrect responses were measured. RESULTS: Repeated measures ANOVAs revealed that after derogatory feedback, ERN-latencies were longer, also when controlling for shame-proneness. Shame-proneness and ERN-amplitudes correlated. LIMITATIONS: Despite the methodological soundness of the present study, its strongest limitation lies in the lack of insight into the subjective level of shame after derogatory feedback. CONCLUSION: The results are discussed in light of punishment sensitivity of shame-prone adolescents. Future research is needed to gain greater insight into the relationship between shame proneness and punishment sensitivity.

I C U but I don't care: Callous-unemotional traits and approach-avoidance behaviour in conduct disorder.

BACKGROUND AND OBJECTIVES: Conduct disorder (CD) is associated with deficits in social-emotional behaviour, such as increased levels of aggression. Callous-unemotional (CU-) traits foster those deficits and contribute to severe rates of instrumental aggression in CD. Previous studies of that increase in aggression have mainly focused on intentional aspects of behaviour. Unintentional behaviour, such as automatic approach and avoidance, has not been taken into account despite being highly relevant for behaviour. Therefore, the relevance of CU-traits for automatic actions and the feasibility of an approach-avoidance-task to measure those actions in CD-patients were investigated in a study series. METHODS: Study 1 22 CD-patients executed an approach-avoidance task, where participants pushed or pulled pictures of emotional faces using a joystick. CU-traits were assessed via parent-report. Study 2 28 CD-patients and 19 typically developing children (TD) executed the AAT. Again, CU-traits were assessed via parent-report. RESULTS: The AAT was a feasible instrument to measure automatic action tendencies and revealed that, while TD-children showed an avoidance bias towards angry faces, CD-patients showed a lack of automatic avoidance of anger. Across the whole sample (TD and CD combined), CU-traits predicted less threat avoidance. LIMITATIONS: The small sample size may have limited the power to detect smaller approach-avoidance tendencies towards other emotions. CONCLUSIONS: The findings suggest that CD is associated with a lack of automatic avoidance of social threat and that CU-traits predict that lack of avoidance. Divergent automatic threat responding might underlie the extreme levels of instrumentally aggressive behaviour observed in CD-patients with distinctive CU-traits.

Cognitive Profiles of Adolescent Inpatients with Substance Use Disorder.

The prevalence of substance abuse is high during adolescence, and several studies have linked the use of alcohol and cannabis in adolescence to different cognitive impairments. To investigate whether specific cognitive deficits can be observed in adolescents with substance use disorder (SUD), we compared the cognitive profiles of inpatient adolescents diagnosed with SUD to a control group matched for sex, age and educational status. The inpatient adolescents received diagnoses of cannabis use disorder, alcohol use disorder or both. We compared the WISC-V profiles of 22 inpatients (45.5% female, Mage: 14.5; SD: 0.8) and the WAIS-IV profiles of 27 inpatients (44.4% female, Mage: 17.1; SD: 0.9) to 49 matched control participants with no diagnosed SUD. At the time of testing, participants were hospitalized for treatment of their SUD and were abstinent for a period of at least 6 weeks. To gain greater power, we jointly analyzed the Verbal Comprehension Index, Working Memory Index, Processing Speed Index and Full Scale IQ as assessed by WISC-V and WAIS-IV. The clinical group performed significantly worse than the control group on all the above indices. When only the group of inpatients was observed, in a model with the factors sex, educational status, presence of a comorbid diagnosis of depression and the number of comorbid diagnoses, only the factor educational status was significantly associated with the Full Scale IQ, whereas the factors sex and a comorbid diagnosis of depression in this group were associated with the Processing Speed Index. The results show that adolescents diagnosed with SUD (cannabis and/or alcohol) display broad cognitive impairments after 6 weeks of abstinence. Future research is required to further explore the role of comorbid diagnoses.

Possible Effects of Bright Light Therapy on Electroencephalogram-Vigilance in the Treatment of Depression in Adolescents: A Pilot Study.

Background: Chronotherapeutic treatments for depression, such as bright light therapy (BLT), are non-invasive and produce almost no side effects. However, study evidence for reliable neurobiological changes associated with treatment response is still rare. Several studies using EEG-vigilance indicate higher arousal and a later decline during resting state in adult depressive patients compared to healthy controls. To our knowledge, there are no study reports on EEG-vigilance in depressive youth to date. Methods: A total of 11 adolescents with depression receiving BLT were compared to 11 age and gender-matched patients with depression receiving treatment as usual (TAU). The BLT was administered in the morning for 2 weeks on five consecutive days per week. The depressive symptomatology was assessed using the Beck Depression Inventory (BDI-II) and the resting state electroencephalogram (EEG) of 20 min was recorded. EEG and BDI-II were assessed before and after 10 days of treatment. Vigilance level and vigilance decline were estimated using the VIGALL toolbox. Results: Brain arousal increased after 10 days of bright light therapy in adolescents with depression. Severe depressive symptoms were associated with higher brain arousal levels; the BDI-II sum score correlated negatively with the amount of drowsiness. Limitations: The sample size was small and participants' brain arousal at baseline was not matched and differed between BLT and TAU groups. Conclusion: The BLT might have an additional effect on brain arousal. EEG-vigilance seems to be a reliable and valid marker for neurobiological changes that are probably associated with depression and its treatment and, therefore, might be of clinical relevance.

Translation and validation of the SCRAM questionnaire in a German adolescent inpatient sample.

Sleep, depressive symptoms and circadian preference are highly interconnected processes. Evidence suggests that, especially in adolescence, all processes should be considered in the assessment and treatment of patients with clinically relevant psychopathology. The SCRAM (Sleep, Circadian Rhythms, and Mood) questionnaire was developed and validated in a student sample as a promising tool to conjointly measure and separate sleep, circadian preference and depression symptomatology. The present study aims to validate a German version of the SCRAM questionnaire in an adolescent psychiatric inpatient sample. A two-step analytic strategy consisting of an exploratory factor analysis EFA followed by confirmatory factor analyses (CFA) was conducted. The EFA was run in the first half of the sample (n = 422, M = 14.92, SD = 1.67). To validate the factor structure of the EFA and the original study, two CFA`s were performed in the second half of the adolescent sample (n = 438, M = 15.07, SD = 1.68). The EFA analysis revealed a 4-factor model with 12 items. Two Sleep items and one Morningness item had cross-factor loadings. The fit indices in the CFA were good using the factor model of the original study, whereas the 4-factor model of the EFA did not converge. The German SCRAM factor model seems structurally sound in an adolescent inpatient sample, but questions remain regarding the role of diagnosis, gender, external correlates, and examining the change scores of the SCRAM scores with treatment. Before this application, further research is needed to replicate the factor structure, investigate test-retest reliability, predictive and discriminant validity and test in more generalizable samples.

Characterization of the L-Arginine/Nitric Oxide Pathway and Oxidative Stress in Pediatric Patients with Atopic Diseases.

INTRODUCTION: L-Arginine (Arg) is a semi-essential amino acid. Constitutive and inducible nitric oxide synthase (NOS) isoforms convert Arg to nitric oxide (NO), a potent vaso- and bronchodilator with multiple biological functions. Atopic dermatitis (AD) and bronchial asthma (BA) are atopic diseases affecting many children globally. Several studies analyzed NO in airways, yet the systemic synthesis of NO in AD and BA in children with BA, AD or both is elusive. METHODS: In a multicenter study, blood and urine were obtained from 130 of 302 participating children for the measurement of metabolites of the Arg/NO pathway (BA 31.5%; AD 5.4%; AD + BA 36.1%; attention deficit hyperactivity disorder (ADHD) 12.3%). In plasma and urine amino acids Arg and homoarginine (hArg), both substrates of NOS, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), both inhibitors of NOS, dimethylamine (DMA), and nitrite and nitrate, were measured by gas chromatography-mass spectrometry. Malondialdehyde (MDA) was measured in plasma and urine samples to evaluate possible effects of oxidative stress. RESULTS: There were no differences in the Arg/NO pathway between the groups of children with different atopic diseases. In comparison to children with ADHD, children with AD, BA or AD and BA had higher plasma nitrite (p < 0.001) and nitrate (p < 0.001) concentrations, suggesting higher systemic NO synthesis in AD and BA. Urinary excretion of DMA was also higher (p = 0.028) in AD and BA compared to patients with ADHD, suggesting elevated ADMA metabolization. DISCUSSION/CONCLUSION: The Arg/NO pathway is activated in atopic diseases independent of severity. Systemic NO synthesis is increased in children with an atopic disease. Plasma and urinary MDA levels did not differ between the groups, suggesting no effect of oxidative stress on the Arg/NO pathway in atopic diseases.

[Use of Electronic Cigarettes (e-cigs) and e-Shishas by Children and Adolescents: Evidence Paper of the Joint Addiction Commission of the German Societies and Professional Associations of Child and Adolescent Psychiatry and Psychotherapy]. / Nutzung elektronischer Zigaretten (E-Zigaretten) und E-Shishas durch Kinder und Jugendliche.

Use of Electronic Cigarettes (e-cigs) and e-Shishas by Children and Adolescents: Evidence Paper of the Joint Addiction Commission of the German Societies and Professional Associations of Child and Adolescent Psychiatry and Psychotherapy Abstract. The particular risks associated with the consumption of electronic cigarettes (e-cigs) in children and adolescents are not sufficiently considered in the health policy discourse. The present article evaluates the current dissemination and consumption patterns of e-cigarettes as well as the health risks attached to children and adolescents. Based on data from current national and international studies, there has been a clear increase in the consumption of e-cigarettes over the past years. This stands in sharp contrast to the overall decline in tobacco consumption among both children and adolescents in Germany. Young people without tobacco experience are now consuming more frequently e-cigarettes than those who occasionally or regularly use tobacco. They also are experimenting more frequently with conventional cigarettes if they have previously consumed e-cigarettes. The largely unregulated availability of e-cigarette products to the newest generation, such as JUUL, led to a dramatic increase in their prevalence among high-school students in the USA. Products with high nicotine content and multiple flavors are being marketed intensively as trendy lifestyle products to young user groups via advertising and social media campaigns. These products are also becoming increasingly relevant in Germany. The success of tobacco prevention in recent years is presently jeopardized by the ongoing effective advertising for e-cigarettes. The Addiction Commission of the German Child and Youth Psychiatric Federations and Scientific Societies therefore call for an immediate, strict, and comprehensive ban of e-cigarette advertising.

Treatment of Adolescents with Concurrent Substance Use Disorder and Attention-Deficit/Hyperactivity Disorder: A Systematic Review.

Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for the development of substance abuse and substance use disorders (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment, and is associated with poor treatment outcomes. In this study, we provide a systematic review of controlled studies on the effectiveness of pharmacological, psychosocial, and complementary treatments of ADHD in adolescents with and without comorbid SUD. In addition, we review the longitudinal association between pharmacotherapy for childhood ADHD and the development of SUD in adolescence and early adulthood. We conducted a systematic review of the research literature published since 2000 using Medline, PsycINFO, and the Cochrane Database of Systematic Reviews databases to select randomized clinical trials, observational studies, and meta-analyses. The quality of the evidence from each study was rated using the SIGN grading system. Based on the limited evidence available, strong clinical recommendations are not justified, but provisionally, we conclude that stimulant treatment in children with ADHD may prevent the development of SUD in adolescence or young adulthood, that high-dose stimulant treatment could be an effective treatment for adolescents with ADHD and SUD comorbidity, that cognitive behavior therapy might have a small beneficial effect in these patients, and that alternative treatments are probably not effective. More studies are needed to draw definitive conclusions that will allow for strong clinical recommendations.