What endocrinologists can do to prevent cardiovascular complications in adults with Prader-Willi syndrome:Lessons from a case series

Context: Prader-Willi syndrome (PWS) is a complex rare genetic syndrome. Mortality in patients with PWS is 3% per year. In nearly half of the patients, the cause of death is of cardiopulmonary origin. Prevention, diagnosis and treatment of cardiovascular (CV) disease in PWS adults is complicated by the behavioral phenotype, reduced ability to express physical complaints, high pain threshold and obesity. Objective: To describe the challenges in prevention, diagnosis and treatment of CV disease in PWS adults, in order to increase awareness and improve medical care. Methods: Retrospective study of medical records of adults visiting the Dutch PWS reference center. Results: We describe the challenges encountered during diagnosis and treatment of four PWS adults with heart failure. All had pre-existent peripheral edema. CV risk factors in these patients were obesity (n=4), type 2 diabetes mellitus (n=2), hypertension (n=2), hypogonadism (n=3) and sleep apnea (n=2). Remarkably, all patients were younger than 40 years during their first cardiac decompensation. All patients presented with progressive shortness of breath and/or orthopnea and progressive pitting edema. In 117 controls with PWS without CV problems, 31% had leg edema. Conclusion: Diagnosing CV problems in PWS adults is challenging. Peripheral edema is common in PWS adults without CV morbidity, which makes edema in general a poor marker for heart failure. However, when edema is of the pitting kind and progressive, this is a strong predictor of cardiac decompensation. We provide practical recommendations for diagnosing and treating CV problems in this vulnerable patient population.</p

Malignancies in Prader-Willi Syndrome:Results From a Large International Cohort and Literature Review

CONTEXT: Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. OBJECTIVE: To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. METHODS: We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy, and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. RESULTS: Seven adults (age range, 18-55 years) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma, and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. CONCLUSION: Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present, such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.</p

Treating Trauma-related Disorders in Later Life: Moving Forward

Among stress-related disorders, post-traumatic stress disorder (PTSD) takes a central position. Although the percentage of older adults suffering from this condition appears to be lower than among younger adults, PTSD among them often presents a serious condition with high comorbidity rates. In this contribution, recent insights into post-traumatic stress disorder among older people as well as psychotherapeutic treatments are discussed. In particular, the results of recently completed investigations are discussed. In this research, treatment outcomes of two psychotherapeutic approaches considered suitable for older PTSD patients (Narrative Exposure Therapy or NET and Present Centered Therapy or PCT) were compared in terms of psychopathology and psychosocial adjustment. For older patients suffering from PTSD with varying backgrounds, both NET and PCT showed the potential for a significant reduction of symptoms (PTSD, depression and subjective distress). Moreover, it was found that older adults can change long-standing beliefs, even after long-past childhood trauma. In a patient’s own words: “I am still here, the past didn’t bring me to my knees”. These findings disconfirm unfounded pessimism regarding psychotherapy in later life. Currently available treatment approaches in later life can be meaningful in improving the quality of life in older adults for years to come

The effectiveness of narrative exposure therapy: a review, meta-analysis and meta-regression analysis

Background: Narrative exposure therapy (NET) is a short-term psychological treatment for post-traumatic stress disorder (PTSD) that has been investigated in various contexts among traumatized refugees and other trauma survivors. Sustained treatment results have been reported, but the methodological quality of the trials needs a more thorough examination. Objective: To evaluate the effectiveness of NET for survivors of trauma, using a quality assessment, an updated meta-analysis, and a meta-regression analysis. Method: Following a systematic literature selection, the methodological quality of the included studies was assessed; Non-controlled and controlled effect sizes (Hedges’ g) were estimated using a random effects model. Predictor analyses were performed. Non-controlled effect sizes for PTSD and depression included symptom change at post-treatment and follow-up time-points. Controlled effect sizes included post-treatment comparisons of NET with non-active and active comparators: both trauma-focused (TF) and non-trauma-focused (non-TF) interventions. Results: The selected studies showed high external validity; methodological quality was equivalent to other guideline-supported TF interventions. In 16 randomized controlled trials, involving 947 participants, large non-controlled effect sizes were found for PTSD symptoms, at post-treatment (g = 1.18, 95% confidence interval [0.87; 1.50]) and follow-up (g = 1.37 [0.96; 1.77]). For depression symptoms, medium non-controlled effect sizes were found, at post-treatment (g = 0.47 [0.23; 0.71]) and follow-up (g = 0.60 [0.26; 0.94]). Post-treatment, NET outperformed non-active comparators and non-TF active comparators for PTSD, but not the combined active comparators. For depression, NET only outperformed non-active comparators. Advancing age predicted better treatment results for PTSD and depression symptoms; a history of migration predicted smaller treatment results for depression symptoms. Conclusions:The findings of this meta-analysis suggest that patients and providers may expect sustained treatment results from NET. Controlled comparisons with other guideline-supported TF interventions are not yet available

Randomised controlled trial comparing narrative exposure therapy with present-centred therapy for older patients with post-traumatic stress disorder

Background Evidence-based treatment and age-specific services are required to address the needs of trauma-affected older populations. Narrative exposure therapy (NET) may present an appropriate treatment approach for this population since it provides prolonged exposure in a lifespan perspective. As yet, however, no trial on this intervention has been conducted with older adults from Western Europe.Aims Examining the efficacy of NET in a sample of older adults.Method Out-patients with post-traumatic stress disorder (PTSD), aged 55 years and over, were randomly assigned to either 11 sessions of NET (n = 18) or 11 sessions of present-centred therapy (PCT) (n = 15) and assessed on the Clinician-Administered PTSD Scale (CAPS) pre-treatment, post-treatment and at follow-up. Total scores as well as symptom scores (re-experience, avoidance and hyperarousal) were evaluated.Results Using a piecewise mixed-effects growth model, at post-treatment a medium between-treatment effect size for CAPS total score (Cohen's d = 0.44) was found, favouring PCT. At follow-up, however, the between-treatment differences were non-significant. Drop-out rates were low (NET 6.7%, PCT 14.3%) and no participant dropped out of the study because of increased distress.Conclusions Both NET and PCT appear to be safe and efficacious treatments with older adults: PCT is non-intrusive and NET allows for imaginal exposure in a lifespan perspective. By selectively providing these approaches in clinical practice, patient matching can be optimised.Declaration of interest None

Psychopathology and resilience in older adults with Posttraumatic Stress Disorder:: A randomized controlled trial comparing Narrative Exposure Therapy and Present-Centered Therapy

Objective: Using data from a randomized controlled trial on psychotherapy for posttraumatic stress disorder (PTSD) in older adults (aged >55), this study aimed at analysing the efficacy of two psychological interventions in terms of self-reported symptoms, comorbid psychopathology and resilience outcomes. Method: Thirty-three outpatients (age 55–81) with PTSD were randomly assigned to eleven sessions of narrative exposure therapy or present-centered therapy. Self-reported symptom severity of PTSD, depression and general psychopathology, along with measures of resilience (self-efficacy, quality of life and posttraumatic growth cognitions), were target outcomes. Harvard Trauma Questionnaire, Beck Depression Inventory, Brief Symptom Inventory, General Efficacy Scale, World Health Organization Quality of Life Assessment and Meaning of War Scale (personal growth) were assessed pre-treatment, post-treatment and at four months follow-up. Because of variable inter-assessment intervals, a piecewise mixed effects growth model was used to investigate treatment effects. Results: Neither post-treatment, nor at mean follow-up, between-group effects were found. At follow-up, significant medium to large within-group effect sizes were found in the NET-group for psychopathology (self-reported PTSD: Cohen’s d = 0.54, p < .01; depression: Cohen’s d = 0.51, p = .03; general psychopathology: Cohen’s d = 0.74, p = .001), but not so in the PCT-group. Resilience (self-efficacy, quality of life and personal growth cognitions) did not significantly change in either group. Conclusions: In older adults with PTSD, the efficacy of NET extended beyond PTSD, reducing not only self-reported symptoms of PTSD but also comorbid depression and general psychopathology

Psychopathology and resilience in older adults with Posttraumatic Stress Disorder:: A randomized controlled trial comparing Narrative Exposure Therapy and Present-Centered Therapy

Objective: Using data from a randomized controlled trial on psychotherapy for posttraumatic stress disorder (PTSD) in older adults (aged >55), this study aimed at analysing the efficacy of two psychological interventions in terms of self-reported symptoms, comorbid psychopathology and resilience outcomes. Method: Thirty-three outpatients (age 55–81) with PTSD were randomly assigned to eleven sessions of narrative exposure therapy or present-centered therapy. Self-reported symptom severity of PTSD, depression and general psychopathology, along with measures of resilience (self-efficacy, quality of life and posttraumatic growth cognitions), were target outcomes. Harvard Trauma Questionnaire, Beck Depression Inventory, Brief Symptom Inventory, General Efficacy Scale, World Health Organization Quality of Life Assessment and Meaning of War Scale (personal growth) were assessed pre-treatment, post-treatment and at four months follow-up. Because of variable inter-assessment intervals, a piecewise mixed effects growth model was used to investigate treatment effects. Results: Neither post-treatment, nor at mean follow-up, between-group effects were found. At follow-up, significant medium to large within-group effect sizes were found in the NET-group for psychopathology (self-reported PTSD: Cohen’s d = 0.54, p < .01; depression: Cohen’s d = 0.51, p = .03; general psychopathology: Cohen’s d = 0.74, p = .001), but not so in the PCT-group. Resilience (self-efficacy, quality of life and personal growth cognitions) did not significantly change in either group. Conclusions: In older adults with PTSD, the efficacy of NET extended beyond PTSD, reducing not only self-reported symptoms of PTSD but also comorbid depression and general psychopathology

Thyroid Function in Adults with Prader-Willi Syndrome;: a Cohort Study and Literature Review

Prader–Willi syndrome (PWS) is a complex genetic syndrome combining hypotonia, hyperphagia, a PWS-specific neurocognitive phenotype, and pituitary hormone deficiencies, including hypothyroidism. The low muscle mass associated with PWS causes a low energy expenditure due to a low basal metabolic rate. Combined with increased energy intake due to hyperphagia, this results in a high risk of obesity and associated cardiovascular disease. To reduce the high mortality in PWS (3% yearly), exercise is extremely important. As hypothyroidism can impair exercise tolerance, early detection is crucial. We performed a literature search for articles on hypothyroidism in PWS, measured thyroid hormone (TH) levels in 122 adults with PWS, and performed a medical file search for medication use. Hypothyroidism (low free thyroxin) was present in 17%, and often central in origin (80%). Triiodothyronine levels were lower in patients who used psychotropic drugs, while other TH levels were similar. One in six patients in our cohort of adults with PWS had hypothyroidism, which is more than in non-PWS adults (3%). We recommend yearly screening of free thyroxin and thyroid-stimulating hormone levels to avoid the negative effects of untreated hypothyroidism on basal metabolic rate, body mass index, and cardiovascular risk. Additionally, we recommend measuring TH concentrations 3–4 months after the start of growth hormone treatment