Extensive Phenotyping for Potential Weight-Inducing Factors in an Outpatient Population with Obesity

Background: Obesity has been associated with miscellaneous weight-inducing determinants. A comprehensive assessment of known obesity-related factors other than diet and physical activity within one cohort is currently lacking. Objectives: To assess the prevalence of potential contributors to obesity and self-reported triggers for marked weight gain in an adult population with obesity and between obesity classes. Methods: In this observational cohort study, we assessed 408 persons with obesity (aged 41.3 ± 14.2 years, BMI 40.5 ± 6.2) visiting our obesity clinic. They were evaluated for use of weight-inducing drugs, hormonal abnormalities, menarcheal age, (high) birth weight, sleep deprivation, and obstructive sleep apnea syndrome (OSAS). We additionally assessed self-reported triggers for marked weight gain and performed genetic testing in patients suspected of genetic obesity. Results: Nearly half of the patients were using a potentially weight-inducing drug, which was also the most reported trigger for marked weight gain. For the assessed hormonal conditions, a relatively high prevalence was found for hypothyroidism (14.1%), polycystic ovary syndrome (12.0%), and male hypogonadism (41.7%). A relatively low average menarcheal age (12.6 ± 1.8 years) was reported, whereas there was a high prevalence of a high birth weight (19.5%). Sleep deprivation and OSAS were reported in, respectively, 14.5 and 13.7% of the examined patients. Obesity class appeared to have no influence on the majority of the assessed factors. Of the genetically analyzed patients, a definitive genetic diagnosis was made in 3 patients (1.9%). Conclusions: A thorough evaluation of patients with obesity yields a relatively high prevalence of various potentially weight-inducing factors. Diagnostic screening of patients with obesi

The narrative of a patient with leptin receptor deficiency: personalized medicine for a rare genetic obesity disorder

Leptin receptor deficiency is a rare genetic disorder that affects the body’s ability to regulate appetite and weight. For patients and their families, the disorder seriously disrupts daily life, however, little is published about this impact. We here report the experiences of a 10.5-year-old girl with leptin receptor deficiency and her family. The diagnosis of this rare genetic obesity had deep impact on the live of the child and her family. It led to a better understanding of the cause of the impaired appetite regulation and early-onset obesity with subsequently less judgement by others and improved cooperation of their social network and school on maintaining a healthy lifestyle for this girl. A strict eating regimen and lifestyle measures resulted in the first year after diagnosis in a significantly decreased BMI, followed by BMI stabilization, still categorized as obesity class three. However, the troublesome challenge on how to manage the disrupting behaviour due to hyperphagia remained. Eventually, due to treatment with targeted pharmacotherapy, i.e., melanocortin-4 receptor agonists, her BMI continued to decrease due to resolving hyperphagia. The daily routine of the family and the atmosphere at home positively changed, as it was no longer dominated by the food-focused behaviour of the child and the adherence to the strict eating regimen. This case report demonstrates the importance and impact of a rare genetic obesity disorder diagnosis in a family. Additionally, it highlights the value of genetic testing in patients with a high suspicion of a genetic obesity disorder as it can eventually lead to personalized treatment, such as guidance by specialized healthcare professionals and educated caregivers or targeted pharmacotherapy

Extensive Phenotyping for Potential Weight-Inducing Factors in an Outpatient Population with Obesity

BACKGROUND: Obesity has been associated with miscellaneous weight-inducing determinants. A comprehensive assessment of known obesity-related factors other than diet and physical activity within one cohort is currently lacking. OBJECTIVES: To assess the prevalence of potential contributors to obesity and self-reported triggers for marked weight gain in an adult population with obesity and between obesity classes. METHODS: In this observational cohort study, we assessed 408 persons with obesity (aged 41.3 ± 14.2 years, BMI 40.5 ± 6.2) visiting our obesity clinic. They were evaluated for use of weight-inducing drugs, hormonal abnormalities, menarcheal age, (high) birth weight, sleep deprivation, and obstructive sleep apnea syndrome (OSAS). We additionally assessed self-reported triggers for marked weight gain and performed genetic testing in patients suspected of genetic obesity. RESULTS: Nearly half of the patients were using a potentially weight-inducing drug, which was also the most reported trigger for marked weight gain. For the assessed hormonal conditions, a relatively high prevalence was found for hypothyroidism (14.1%), polycystic ovary syndrome (12.0%), and male hypogonadism (41.7%). A relatively low average menarcheal age (12.6 ± 1.8 years) was reported, whereas there was a high prevalence of a high birth weight (19.5%). Sleep deprivation and OSAS were reported in, respectively, 14.5 and 13.7% of the examined patients. Obesity class appeared to have no influence on the majority of the assessed factors. Of the genetically analyzed patients, a definitive genetic diagnosis was made in 3 patients (1.9%). CONCLUSIONS: A thorough evaluation of patients with obesity yields a relatively high prevalence of various potentially weight-inducing factors. Diagnostic screening of patients with obesity could therefore benefit these patients by potentially reducing the social stigma and improving the outcomes of obesity treatment programs by tackling, where possible, the weight-inducing factors in advance

A comprehensive diagnostic approach to detect underlying causes of obesity in adults

Obesity is a worldwide growing problem. When confronted with obesity, many health care providers focus on direct treatment of the consequences of adiposity. We plead for adequate diagnostics first, followed by an individualized treatment. We provide experience-based and evidence-based practical recommendations (illustrated by clinical examples), to detect potential underlying diseases and contributing factors. Adult patients consulting a doctor for weight gain or obesity should first be clinically assessed for underlying diseases, such as monogenetic or syndromic obesity, hypothyroidism, (cyclic) Cushing syndrome, polycystic ovarian syndrome (PCOS), hypogonadism, growth hormone deficiency, and hypothalamic obesity. The most important alarm symptoms for genetic obesity are early onset obesity, dysmorphic features/congenital malformations with or without intellectual deficit, behavioral problems, hyperphagia, and/or striking family history. Importantly, also common contributing factors to weight gain should be investigated, including medication (mainly psychiatric drugs, (local) corticosteroids, insulin, and specific β-adrenergic receptor blockers), sleeping habits and quality, crash diets and yoyo-effect, smoking cessation, and alcoholism. Other associated conditions include mental factors such as chronic stress or binge-eating disorder and depression.Identifying and optimizing the underlying diseases, contributing factors, and other associated conditions may not only result in more effective and personalized treatment but could also reduce the social stigma for patients with obesity

Impact of the COVID-19 pandemic and related lockdown measures on lifestyle behaviors and wellbeing in children and adolescents with severe obesity

Introduction: COVID-19 lockdown measures have large impact on lifestyle behaviors and wellbeing of children. The aim of this mixed-methods study was to investigate the impact of COVID-19 lockdown measures on eating styles and behaviors, physical activity (PA), screen time, and health-related quality of life (HRQoL) in children (0-18 years) with severe obesity. Methods: During the first COVID-19 wave (April 2020), validated questionnaires were completed and semi-structured telephone interviews were conducted with parents of children with severe obesity (adult BMI-equivalent ≥35kg/m2) and/or with the children themselves. Changes in pre-pandemic versus lockdown scores of the Dutch Eating Behavior Questionnaire Children (DEBQ-C), Pediatric Quality of Life Inventory (PedsQLTM), and Dutch PA Questionnaire were assessed. Qualitative analyses were performed according to the Grounded Theory. Results: Ninety families were approached of which 83 families were included. Characteristics of the included children were: mean age 11.2 ± 4.6 years, 52% female, mean BMI SD-score +3.8 ± 1.0. Emotional, restrained, and external eating styles, HRQoL, and (non-educational) screen time did not change on group level (all p>0.05). However, weekly PA decreased (mean difference -1.9 hours/week, p=0.02), mostly in adolescents. In the majority of children, mean weekly PA decreased to ≤2 hours/week. Children with high emotional and external eating scores during lockdown or pre-existent psychosocial problems had the lowest HRQoL (p<0.01). Qualitative analyses revealed an increased demand for food in a significant proportion of children (n=21), mostly in children <10 years (19/21). This was often attributed to loss of daily structure and perceived stress. Families who reported no changes (n=15) or improved eating behaviors (n=11) attributed this to already existing strict eating schemes that they kept adhering to during lockdown. Conclusion: This study shows differing responses to COVID-19 lockdown measures in children with severe obesity. On group level, PA significantly decreased and in substantial minorities eating styles and HRQoL deteriorated. Children with pre-existent psychosocial problems or pre-pandemic high external or emotional eating scores were most at risk. These children and their families should be targeted by health care professionals to minimize negative physical and mental health consequences

Effects of glucagon-like peptide-1 analogue treatment in genetic obesity:A case series

Obesity is highly prevalent and comes with serious health burden. In a minority, a genetic cause is present which often results in therapy‐resistant obesity. Liraglutide is a glucagon‐like peptide‐1 (GLP‐1) analogue, which has beneficial effects on satiety and weight in common obesity. We present the effects of GLP‐1 analogues in adults with a molecularly proven genetic cause of their overweight or obesity. All patients were treated with liraglutide 3.0 mg daily, in addition to intensive supportive lifestyle treatment. Anthropometrics, metabolic parameters, resting energy expenditure (REE), side effects, and subjectively reported satiety and quality of life were assessed. Two patients with 16p11.2 deletion syndrome and two patients with heterozygous pathogenic melanocortin‐4 receptor variants were treated. At baseline, their age ranged between 21 and 32 years and body mass index (BMI) ranged between 28.1 and 55.7 kg/m(2). At follow‐up (ranges 43 weeks–12 years), a mean change in BMI and waist circumference was observed of −5.7 ± 3.8 kg/m(2) and −15.2 ± 21.1 cm, respectively. All patients achieved ≥5% weight loss, three of them lost ≥10% of their body weight. All patients reported improved quality of life and three of them reported ameliorated satiety. Moreover, improvement of glycaemic control and dyslipidaemia were seen. In two patients, REE before and during treatment was measured, which either increased (+26% of predicted REE) or decreased (−18% of predicted REE). Two patients experienced mild side effects for a brief period. In conclusion, our case series shows beneficial effects of GLP‐1 analogues on weight, metabolic parameters and quality of life in all four patients with genetic obesity

Functional Analysis of the SIM1 Variant p.G715V in 2 Patients With Obesity

CONTEXT: Single-minded homologue 1 (SIM1) is a transcription factor with several physiological and developmental functions. Haploinsufficiency of SIM1 is associated with early-onset obesity with or without Prader-Willi-like (PWL) features and may exhibit incomplete penetrance. CASE DESCRIPTION: Next-generation sequencing was performed for 2 male patients with obesity, including 1 man presenting with intellectual disability (ID), body mass index (BMI) of 47.4, and impulse-control disorder, and the other man with early obesity (BMI of 36); sequencing revealed a missense variant in SIM1 (c.2144G>T; p.G715V) in both individuals. Previous studies have identified several disease-associated variants that fall near the p.G715V variant within the C-terminal domain of SIM1. We examined p.G715V variant stability and activity in a doxycycline-inducible stable cell line transfected with an artificial reporter construct and either ARNT or ARNT2 as a partner protein. CONCLUSIONS: Functional testing of the p.G715V variant revealed a significant reduction in SIM1-mediated transcriptional activity. We also generated the first ab initio hybrid protein model for full-length SIM1 to show the predicted spatial relationship between p.G715V and other previously described variants in this region and identified a putative mutation hotspot within the C-terminus. Significant clinical heterogeneity has been observed in patients with SIM1 variants, particularly with regards to the PWL phenotype. In the patient with ID, a second variant of uncertain significance in CHD2 was identified that may contribute to his ID and behavioral disturbances, emphasizing the role of additional genetic modifiers

Erratum: Identifying underlying medical causes of pediatric obesity: Results of a systematic diagnostic approach in a pediatric obesity center (PLOS ONE (2020) 15:5 (e0232990) DOI: 10.1371/journal.pone.0232990)

The affiliation for the twelfth author is incorrect. Erica L. T. van den Akker is not affiliated with #2 and #3 but with #1: Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands and #4: Division of Endocrinology, Department of Pediatrics, Erasmus MC-Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands

SATEENKAAREN PÄÄSTÄ LÖYTYY KULTAA: Tutkimus suomalaisesta saattohoidosta

Saattohoitoon erikoistuneet hoitokodit muovaamassa suomalaista hoitokulttuuria Tutkimuksessa tarkastellaan kuolevan potilaan hoitamista suomalaisissa saattohoitokodeissa. Saattohoitokodit aloittivat toimintansa Suomessa 1980-luvulla. Tutkimuksessa tuodaan esille ensimmäisten saattohoitokotien perustamiseen ja suunnitteluun liittyvää lähihistoriaa Pirkanmaan Hoitokodista Tampereelta, Terhokodista Helsingistä ja Karinakodista Turusta. Tutkimus on ensimmäinen suomalaista saattohoitokulttuuria käsittelevä hoitotieteellinen tutkimus. Työssä on käytetty etnografista tutkimusmetodia. Monipuolista ja laajaa tutkimusaineistoa on analysoitu ja tulkittu mm. kuva-analyysiä soveltaen. Saattohoitoympäristöjen visuaalinen viestintä ja symboliikka tulee voimakkaasti esille tutkimuksen kokonaisuudessa. Tutkimuksessa kysytään, mitä saattohoitokodeissa tapahtuu, mitä tehtäviä kuoleman kynnyksellä on, millaista hoitamista saattohoitoyhteisöt arvostavat, millaisia ympäristöjä saattokodit ovat sekä mitä potilaat ja heidän omaisensa saattovaiheen hoidolta odottavat. Kiinnostava kysymys on, millaisen muodon brittiläisestä hospice-ideologiasta lähtöisin oleva hoitomuoto suomalaisissa saattohoitokodeissa saa. Hoidon keskiössä potilas ja perhe Suomalaisen saattohoidon keskiössä on potilas ja hänen perheensä. Avainsana olemiselle ja tekemiselle on yhdessä. Saattohoidon peruslähtökohtana on potilaan fyysisten, psyykkisten sosiaalisten, henkisten ja hengellisten ulottuvuuksien tarpeista lähtevä hoito. Perheelle ja potilaalle pyritään antamaan erilaisia mahdollisuuksia käydä läpi ja hyväksyä kuoleman väistämättömyys, mutta keskeneräisenäkin on oikeus kuolla. Potilaan yksityisyys on saattohoitokodeissa pyhä ja loukkaamaton. Rakkautta, lämpöä, myötätuntoa ja tukea potilas saa läheisiltään ja hoitohenkilöstöltä. Työyhteisöön kuuluvat oleellisena osana myös vapaaehtoistyöntekijät. Saattohoidon toimintakulttuuri on monimuotoista. Arjen traditioihin kuuluvat juhlat, erilaiset värikkäät tapahtumat ja tilaisuudet. Kuoleman lähellä elämää kannattaa juhlia. Saattohoitokodeissa myös tavallinen arki saa pyhäpäivän arvon. Saattohoidon tarkoituksena on tukea, vahvistaa ja rauhoittaa kuolemaa lähestyvää potilasta ja hänen läheisiään. Tukemisen muodot ovat konkreettisen hoitoavun ja tukitoiminnan lisäksi kuuntelemista, ystävällisiä sanoja ja erilaisia sanattomia viestejä. Suoraa sanallista puuttumista ihmisen yksityisiin, sisäisiin prosesseihin vältetään, sillä saattohoitoajattelun mukaan jokaisella tulee olla oikeus rakentaa kuolemantalonsa itse. Rauhallinen kuolema on saattohoidon keskeinen tavoite. Perhettä tuetaan myös potilaan kuoleman jälkeen. Hoitoympäristö puhuttelee ja viestii kuolemasta Saattohoitokotien julkiset tilat tekevät vaikutuksen kävijöihin. Jo pelkkä ympäristö puhuttelee ja pysähdyttää. Joillekin hoitokoti on kuin kokemus taivaan esikartanoista , joitakin se ahdistaa. Jokaisessa kolmessa saattohoitokodissa on mm. viherpuutarha ja jossakin muodossa toteutettu vesielementti. Taustaäänenä voi olla vain hiljalleen soliseva, virtaava vesi. Saattohoitokotien symboliikka pakottaa ajattelemaan kuolemaa. Kuolemasta viestivät mm. palavat kynttilät ja lasi- tai keramiikkalinnut. Saattohoitokodissa kuolema on aina läsnä. Hoitohenkilöstön voimana oma työnäky ja sitoutuminen saattohoitoideologiaan Saattohoidon parissa työskenteleviä yhdistää halu auttaa ihmistä ja tehdä jotakin todella tärkeää. Oma työnäky, lähimmäisenrakkaus ja kuolevan hoitamiseen liittyvän työn haasteellisuus auttavat jaksamaan. Työyhteisön voimana on sekä perussuomalainen niskavuorelaisuus että sitoutuminen yhteiseen asiaan, saattohoitoideologiaan. Tutkimusajankohtana haastateltu henkilökunta oli ollut saattohoitotyössä hoitokotien perustamisesta lähtien ja siksi yhteisvastuuseen ja kuolevan hoitamiseen voimallisesti sitoutuneita. Ensimmäisten suomalaisten saattohoitokotien omaksuma, inhimilliseen ja hyvään hoitamiseen pyrkivä kuolevan potilaan hoito ja hoitokulttuuri on yllättävää monimuotoisuudessaan ja toiminnallisuudessaan. Siihen kuuluu olennaisena osana myös varsinaiseen saattohoitoyhteisöön kuulumattomien henkilöiden tuki ja osallisuus, mikä merkitsee suomalaisittain, että veljeä ei jätetä. Lähitulevaisuudessa tapahtuva hoitajakunnan sukupolvenvaihdos tuo eteen uusia kysymyksiä sekä hoidon arvoista, hoitokulttuurista että kuolevan hoitamisen käytännön järjestämisestä terveydenhuollon eri alueilla.The care of dying patients in the form of hospice care began in Finland in the late 1980s, when the first of Finland s four hospices was opened. The present ethnography aimed at generating information on the substance and nature of Finnish hospice care. The research is a monograph in the field of health sciences, and the data were collected using the ethnographic method in three Finnish hospices. The ethnography depicts care culture, care philosophy, care environment, the traditions and different types and dimensions of hospice care from the perspective of nursing science. The purpose of the research was to depict and highlight terminal care provided in hospices and to contribute to understanding of the care of dying patients. The ideology adopted in Finnish hospices stems from that used in British hospices. While bearing in mind the premises underlying the hospice ideology, the research task does not involve comparisons between care cultures. Hospice care has received much praise from patients and their significant others as an exemplar of good care. The research addresses the components and essence of good care in Finnish hospices. Data were collected mainly in a hospice in Tampere (1996-2000), but also in the two other Finnish hospices in Helsinki and Turku. Altogether 35 persons (n=35) were interviewed. The research also drew on interview data from hospice care patients (n=6), collected by the researcher in 1995. Interviewees were selected from the hospices in a naturalistic way during the research process depending on the preliminary analyses, the researcher s conclusions and the new questions brought about by the research process. The field work and data collection phases were guided by four relatively broad research questions, formulated at the beginning of the research. The research explores the substance of hospice care in Finnish nursing facilities adhering to the hospice ideology; the care ideology represented by Finnish hospice care; the elements embodied in the care environment; and the traditions and rituals of end-of-life care in hospices. The research addresses the tasks involved when a p! atient approaches death, the values of the hospice community and the expectations of patients and their significant others from hospice care. The research environment and communication in hospice care were also examined through images and image analysis. The interview data were analyzed using content analysis and image analysis using the method depicted by Anttila (1998). The research questions were found to be relevant with respect to the purpose of the study. The results showed that hospice care pays individual attention to patients and is family-centred. Hospice care is based on the dying patient s physical, psychological, social and spiritual needs. Personalized pain management and good basic nursing are an essential component of good care. The dying patient s family is emphasized as a care resource. The family is supported by contacting them in different ways after the patient s death. The hospice community is comprised of an interdisciplinary team of experts, strongly committed to the hospice ideology, and of hospice volunteers, essential to the operations. The cultural versatility and subtlety of hospice care stem from collaboration with various actor groups through cultural programmes and visits. Celebrations and a festive atmosphere are part of the hospice s everyday life. The support and involvement of those who are not members of the actual hospice community are an essential element of hospice care. The hospice day centre, run by hospice volunteers, has had a crucial role in the development of Finnish hospice culture. The centre is also open to home hospice patients and their families. Much attention is paid to the furnishings and aesthetic qualities of hospices. Hospices aim to provide patients with a comfortable, home-like and safe care environment, good care and pain relief and the possibility to experience a peaceful death. As care environments, hospices send out strong messages and are marked by symbols of death. Communication in hospice care aims at soothing the patients and significant others, but also involves a great deal of direct and non-verbal messages that compel to consider the ever present death. The Finnish hospices are characterized by charity, compassion and the traditional Finnish Niskavuori ethos