In a population prevalence questionnaire study we demonstrated that constipation and fecal incontinence are common problems in the general Swedish population with a similar magnitude as in other Western countries. 95.6% of the population had between three bowel movements per day and three per week. Constipation was mostly defined by “hard stools” and “the need of using laxatives”. Irritable Bowel Syndrome (IBS) is characterized by abdominal pain/discomfort and abnormal bowel habits. The diagnostic criteria of IBS are based on clinical symptoms. Division of IBS patients into symptom subgroups appears important as their bowel symptoms are characterized by heterogeneity. International criteria to subgroup IBS (Rome II) are based on expert consensus and not on evidence. We investigated the variation of stool consistency and defecatory symptoms in 135 IBS patients by symptom diary cards. Most patients had alternating stool consistency. When subgroups were based on stool consistency, all kinds of defecatory symptoms (straining, urgency, and feeling of incomplete evacuations) were frequently present in all subgroups. Stool frequency was in the normal range in the majority of patients. We propose that IBS subgroups should be based on stool consistency. We suggest that Rome II supportive criteria must be reconsidered as the determination of presence or absence of specific symptoms does not work as an instrument for categorization of IBS patients into diarrhoea- and constipation-predominant. We also propose that abnormal stool frequency should be excluded to define subgroups of IBS. Alternating stool consistency and presence of different defecatory symptoms, regardless of stool consistency should be included as criteria for IBS. Stress is known to play an important role in the onset and modulation of IBS symptoms. From experimental studies there is evidence for a stress-dependent alteration of visceral sensitivity. The biological mechanisms responsible for the causal link between stress and IBS symptoms are not completely understood, but the hypothalamic-pituitary-adrenocortical axis and the autonomous nervous system seem to play a prominent role in the pathophysiology of IBS. We investigated visceral sensitivity and the effect of repeated maximal tolerable rectal distensions on salivary cortisol levels and skin conductance in patients with IBS, chronic constipation and healthy volunteers. We found that the expectancy of the experimental situation per se (provocation of bowel symptoms by rectal distensions) compared to non-experimental days at home measured as salivary cortisol had a high impact on the level of arousal in IBS. IBS patients had higher skin conductance values than controls in the beginning of distension series and lower rectal thresholds for first sensation, urge and discomfort than healthy controls and constipation patients. IBS patients demonstrated habituation to repeated subjective maximal tolerable rectal distensions according to sympathetic activity although patients continued to rate their discomfort as maximal. Constipation patients had lower sympathetic activity than IBS patients before and during repeated rectal distensions. None of the groups demonstrated a significant increase in cortisol after repetitive rectal distensions. We conclude that Rome II supportive criteria for IBS should be reconsidered according to our findings. IBS patients are more sensitive to pre-experimental stress than healthy controls and patients with constipation. This should be considered in the design of experimental IBS studies. IBS patients habituated to subjective maximal tolerable, repetitive rectal distensions with decreasing sympathetic activity. Since responses to repeated stimuli of close-to-pain intensities are resistant to habituation this finding could be caused by psychological influences on perception, that is, perceptual response bias.

The aim of the present study was to investigate all long-term institutions in the county of Västerbotten, Northern Sweden, to give a detailed description of the institutionalized population with respect to motor functions, vision, hearing, speech, ADL-functions, prevalence of psychiatric symptoms and behavioral disturbances, staff work load, use of psychoactive drugs and prevalence of dementia. Another aim was to select some specific 'problem areas' in the nursing care of demented patients for further descriptive and interventional studies. For this reason, morning care procedure (hygiene, dressing), meal behavior (eating, communication), nutrition, constipation and relocation between institutions were selected. The results of the study have been reported in six papers summarized below: I.The study has shown that the proportion of demented patients is increasing in longterm institutions in Sweden. Furthermore, demented patients were shown to be more impaired in all rated functioning abilities and exhibited more psychiatric symptoms and behavioral symptoms. A high proportion of the demented probands were also prescribed psychoactive drugs, i.e. neuroleptics. II. Five patients with Alzheimer-type dementia were monitored during morning care. A 12-step classification system was developed to be used as a guide to understand and determine abilities essential for performance of morning care for demented patients. The quantitative assessment showed that none of the patients were able to manage morning care independently, but there was a wide variation in their highest level of performance. III. Five patients with Alzheimer-type dementia were observed (video taped) during their meals in a changed meal milieu and with new meal routines. When the patients ate without staff participation, the two least demented patients became 'caregivers'. When two mental nurses joined the group, first in civil clothes and then in white uniforms, the patients dropped their roles as helpers. The patients were able to compose complete meals in 0-79 per cent of the meals. The conversation during the meals could be characterized as incomplete, with short sentences and a lot of breaks. Sixty-three per cent of all utterances were about food and eating and almost all conversation concerned the present time. IV. Thirty-three psychogeriatric patients, with severe constipation were given a high- bran bread instead of their accustomed laxatives. During the high-bran treatment period, the number of bowel evacuations and the volume of faeces increased. The total laxative consumption decreased by 93 per cent. V. Nutritional status and dietary intake were studied in a sample of severely demented, institutionalized patients. Energy and /or protein malnutrition was found in 50 per cent of the patients. The mean energy intake was 2059 kcal. Malnourished patients had had four times as many infectious periods during their hospital stay as patients without malnutrition. Thirty-nine of 44 patients lost weight during their hospital stay. VI. Thirty-three psychogeriatric patients were followed for 36 weeks after relocation from a mental hospital to two newly built nursing homes. An intensive pre-relocation program was performed. No negative effects of the relocation were found. On the contrary, the relocated group improved their ADL-functions after the transfer. Based upon the above cited studies, a model for nursing care of demented patients is presented. / <p>S. 1-45: sammanfattning, s. 46-192: 6 uppsatser</p> / digitalisering@umu

The main purpose of this thesis was to study, whether drinkable yoghurt enriched with probiotic bacteria could have any effect on constipation and body weight (BW) among older people with dementia. Further, it concerns poor nutritional status among older people with physical and cognitive impairments and its relationship with factors commonly occur in older people living in residential care facilities. It also discusses how body composition changes with ageing and the associations between changes in muscle mass and functional balance after a high-intensity weight-bearing exercise program (the HIFE program) and the ingestion of an additional milk-based protein-enriched energy supplement. A six-month feasibility study that included a probiotic drink was performed among 15 old people who were living in special units for people with dementia and who all had constipation. The effects of the probiotic drink on stool habits, and BW were studied. The outcome measures were followed daily for bowel movements and at three and six months for BW. The staff found the study easy to carry out and that the drink was well accepted by the participants. No convincing beneficial effects on stool habits were observed. In addition, a mean BW loss of 0.65 kg/month was registered. A poor nutritional intake, low physical activity level, and an over-night fast of almost 15 hours, 4 hours longer than recommended were also observed. As a part of the FOPANU Study (Frail Older People-Activity and Nutrition Study), a randomized controlled trial was carried out in Umeå - the associations between nutritional status and factors common among old people with physical and cognitive impairments living in residential care facilities was studied. Assessments were made of nutritional status using the Mini Nutritional Assessment (MNA) scale, fat-free mass (FFM) and fat mass (FM) using both bioelectrical impedance spectroscopy (BIS) and skinfold thickness measurements. The effects of a high- intensity functional exercise program with an additional protein-enriched milk drink on ability to build muscle mass were evaluated. Analyses were made to investigate whether nutritional status, assessed using the MNA scale, was associated with medical conditions, drugs, activities of daily living (Barthel ADL index), cognitive impairment (Mini Mental State Examination (MMSE)), and depressive symptoms (Geriatric Depression Scale (GDS)) at baseline. The associations were assessed with multiple linear regression analyses with additional interaction analyses. An independent association was found between poor nutritional status and having had a urinary tract infection (UTI) during the preceding year and being dependent in feeding for both women and men, and having lower MMSE scores for women. A large proportion of the participants, were at risk of malnutrition or were already malnourished. Women, but not men, had significantly lower Fat-Free Mass Index (FFMI) and Fat Mass Index (FMI) with age. Bioelectrical impedance spectroscopy results correlated with skinfold thickness measurements, but on different levels on value for FM%. Despite the high-intensity exercise had long-term effects (at six months, three months after the exercise) on functional balance, walking ability and leg strength. No effects on muscle mass and no additional effects from the protein-enriched drink could be observed after the three months of high intensity exercise. A negative, long-term effect on the amount of muscle mass and BW was revealed at six months (three months after the intervention had ended). The effects from the exercise did not differ for participants who were malnourished. No statistical interactions were observed between sex, depression, dementia disorder, and nutritional status, and the level of functional balance capacity on the outcome at three or six months. In summary, the majority of the included older people with dementia had a low dietary intake, low physical activity level, and lost BW despite receiving a probiotic drink supplement every day for six months. The supplementation had no detectable effect on constipation. Among the participants in the FOPANU Study, UTI during the preceding year was independently associated with poor nutritional status. Being dependent in feeding was associated with poor nutritional status as were lower MMSE scores for women but not for men. Despite the high-intensity exercise program had long-term effects on the fysical function was no effect on the amount of muscle mass at three months observed. The FFM and FM expressed as indexes of body height were inversely related to age for women, but not for men. A high-intensity exercise program did not have any effect on the amount of muscle mass. The ingestion of a protein-enriched drink immediately after exercise produced no additional effect on the outcome and the results did not differ for participants who were malnourished. The negative long-term effect on amount of muscle mass, and BW, indicate that it is necessary to compensate for increased energy demands during a high-intensity exercise program. High age, female sex, depression, mild to moderate dementia syndrome, malnutrition, and severe physical impairment do not seem to have a negative impact on the effect of a high-intensity functional weight-bearing exercise program. Consequently, people with these characteristics in residential care facilities should not be excluded from training and rehabilitation including nutrition. More research is needed in large randomized controlled trials to further explore the association between energy balance and malnutrition among frail old people, with a special focus on UTI and constipation, but also to study how physical exercise affects older people’s nutritional status. / Embargo

Masters Research - Masters of Medical Science / The goal of this thesis is to report on research that explored the role of cow’s milk protein in children with chronic functional constipation. The research consisted of a systematic review of the literature, two clinical crossover trials, and a qualitative exploration of the lived experience of following a milk-free diet. Chapter 1 provides the introduction to both allergy and constipation, and the relationship between the two. Causes of constipation can be organic or functional (1). Organic causes of constipation occur in relation to a primary disease classification such as endocrine or metabolic disorders, neurologic disorders, anatomic malformation, collagen vascular disease and some drugs (for example, opiates). Chronic functional constipation is defined as having one bowel motion every three to 15 days (2) and is characterised by painful bowel movements or strain in defecation, hard stools with increased diameter or pellets, and occurs with or without soiling (3). This functional constipation is defined as chronic when it persists for greater than two weeks (4). Chapter 2 details the methods used in searching the literature for evidence for a role of cow’s milk consumption in chronic functional constipation in children from 1980 to 2006. This was published as a systematic review. The literature surrounding cow’s milk and constipation was found to be limited. None of the studies previously conducted were population-based or structured to provide evidence-based evaluation or treatment guidelines at either the general practitioner or paediatric specialist level. The strongest evidence found was a double blind randomised control trial conducted by Iacono and colleagues (3). The research study by Iacono and colleagues (3) provides evidence of an association between cow’s milk and constipation. The following research questions were developed from the systematic review: 1. Can the results of the Iacono and colleagues study of children with chronic functional constipation that respond to the replacement of cow’s milk protein with soy be replicated in the Australian setting? 2. Does cow’s milk β casein A1 cause constipation in children with chronic functional constipation? 3. What are the immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein in children? 4. What factors affect the feasibility of parents administering a cow’s milk protein free diet to their children? The four questions were addressed by two different dietary crossover trials and a qualitative study. Chapter 3 describes the participants recruited and the methods used for the crossover trials investigating milk protein and paediatric chronic functional constipation including details of the primary outcome measure (number of bowel motions during a two-week trial period) and secondary outcome measures (biochemical, immunological and faecal analysis). Chapter 4 describes the results of Trial 1, which replicated the Iacono and colleagues study in the Australian setting, investigating the effects of soy and cow’s milk β-casein A1 in children with chronic functional constipation. One hundred percent of participants experienced resolution of their constipation during the soy milk condition compared with 68% experiencing resolution during the soy milk condition in the Iacono and colleagues study (n=65). Thirteen participants were recruited to Trial 1. Nine participants returned constipation diaries for the study period. The mean (SD) number of stools for each of the conditions was: baseline, 5.1 (1.4); cow’s milk 9.9 (4.4); washout 13.0 (5.2); and soy milk 15.1 (5.0). The differences between the three dietary conditions were statistically significant, p=0.03. The results confirmed the hypothesis that children in the Australian setting with chronic functional constipation unresponsive to the usual treatments, respond to the removal of cow’s milk protein from the diet. Chapter 5 describes the results of Trial 2, the double blind crossover trial comparing the effects of cow’s milk β-casein A1 and cow’s milk β-casein A2 in children with chronic functional constipation. Thirty-nine participants were recruited to Trial 2 and 26 participants returned constipation diaries for the trial period. Unlike the soy result, the cow’s milk β casein A2 did not give 100% resolution of constipation, in fact, the percentage resolution was almost identical to the cow’s milk β casein A1 result. The fact that some children responded during the cow’s milk casein A1 condition in both trials could be caused by a threshold effect, given it was likely that participants were consuming less cow’s milk protein during the trial (400 mL with elimination of all other sources of cow’s milk protein) than on their pre-trial diet. Resolution with both the cow’s milk β casein A1 and cow’s milk β casein A2 conditions suggests that these children are able to tolerate some cow’s milk protein before the symptom of constipation occurs. This could be a food intolerance type reaction or there is some other component in cow’s milk that is causing the problem in these children. Chapter 6 describes a qualitative study of the feasibility for mothers to administer a cow’s milk protein free diet to their children. The experiences of mothers following a cow’s milk protein free diet to assist in the management of chronic functional constipation in children were reported. A number of themes were identified that are useful to health professionals educating families. Mothers found the removal of cow’s milk protein from the diets of their children challenging but persevered due to the potential benefit to their children. Many mothers planned to continue post study with a modified approach to the cow’s milk protein free diet by allowing some cow’s milk protein in the diet to make the diet more acceptable to the family but not as much as the pre-trial diet. These experiences provide health professionals with valuable insights and ideas to assist their patients to manage a cow’s milk protein free diet. Chapter 7 discusses all aspects of the research including any limitations. The results of Trial 1 confirmed the hypothesis that children in the Australian settling with chronic functional constipation unresponsive to the usual treatments respond to the removal of cow’s milk protein from the diet. Therefore, cow’s milk protein is involved in the aetiology of constipation in these children. All the study participants demonstrated an absence or low level of normal gut flora, which may affect bowel regularity. Further research into species present and absent may provide further explanations to the lack of bowel regularity in these children. The immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein requires further investigation. Although the number of statistically significant variables between the conditions was low, there was a high degree of abnormality. Further investigations are needed, including research into food intolerance reactions that affect the nerve endings in the bowel. The results in Trial 1 and Trial 2 are suggestive of an involvement of blood factors including platelets and monocytes. Other children may have a chronic Streptococcus A infection which may be contributing to constipation as well as to liver function abnormalities. Liver function abnormalities were observed for some participants in both trials, independent of milk condition. The extent to which the research questions have been answered is evaluated in Chapter 7, which includes the conclusions and recommendations of this research. In brief, the findings were: • Children with chronic functional constipation that is unresponsive to the traditional treatments should trial a cow’s milk protein free diet for at least two weeks to determine whether this may resolve the constipation. During this period, the numbers and form of bowel motions should be recorded and results compared to a one week record collected prior to commencing the cow’s milk protein free diet. • Due to the complicated nature of a cow’s milk protein free diet, especially the number of processed foods which contain hidden cow’s milk protein, consultation with a dietitian is essential for implementation of this diet. The dietitian should consider educating the patient’s family, both parents and siblings, to ensure the best outcome in terms of acceptance and compliance of the diet, and provide adequate resources. • If this dietary modification is successful for the child and alleviates constipation, consultation with a dietitian is recommended to determine the amount tolerated and nutritional adequacy of the diet. Soy milk is recommended as a substitute for cow’s milk and a probiotic needs to be prescribed to assist with the normalisation of gut flora. • Education of health professionals such as general practitioners, paediatricians, and paediatric continence nurses, regarding a cow’s milk protein free diet for chronic functional constipation, is essential to support the child and his/her family and integral to the success of this strategy. The findings of this research will be published in the scientific literature and as conference presentations. It is hoped that these findings will assist in the management of children with chronic functional constipation unresponsive to the traditional treatments.

Masters Research - Masters of Medical Science / The goal of this thesis is to report on research that explored the role of cow’s milk protein in children with chronic functional constipation. The research consisted of a systematic review of the literature, two clinical crossover trials, and a qualitative exploration of the lived experience of following a milk-free diet. Chapter 1 provides the introduction to both allergy and constipation, and the relationship between the two. Causes of constipation can be organic or functional (1). Organic causes of constipation occur in relation to a primary disease classification such as endocrine or metabolic disorders, neurologic disorders, anatomic malformation, collagen vascular disease and some drugs (for example, opiates). Chronic functional constipation is defined as having one bowel motion every three to 15 days (2) and is characterised by painful bowel movements or strain in defecation, hard stools with increased diameter or pellets, and occurs with or without soiling (3). This functional constipation is defined as chronic when it persists for greater than two weeks (4). Chapter 2 details the methods used in searching the literature for evidence for a role of cow’s milk consumption in chronic functional constipation in children from 1980 to 2006. This was published as a systematic review. The literature surrounding cow’s milk and constipation was found to be limited. None of the studies previously conducted were population-based or structured to provide evidence-based evaluation or treatment guidelines at either the general practitioner or paediatric specialist level. The strongest evidence found was a double blind randomised control trial conducted by Iacono and colleagues (3). The research study by Iacono and colleagues (3) provides evidence of an association between cow’s milk and constipation. The following research questions were developed from the systematic review: 1. Can the results of the Iacono and colleagues study of children with chronic functional constipation that respond to the replacement of cow’s milk protein with soy be replicated in the Australian setting? 2. Does cow’s milk β casein A1 cause constipation in children with chronic functional constipation? 3. What are the immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein in children? 4. What factors affect the feasibility of parents administering a cow’s milk protein free diet to their children? The four questions were addressed by two different dietary crossover trials and a qualitative study. Chapter 3 describes the participants recruited and the methods used for the crossover trials investigating milk protein and paediatric chronic functional constipation including details of the primary outcome measure (number of bowel motions during a two-week trial period) and secondary outcome measures (biochemical, immunological and faecal analysis). Chapter 4 describes the results of Trial 1, which replicated the Iacono and colleagues study in the Australian setting, investigating the effects of soy and cow’s milk β-casein A1 in children with chronic functional constipation. One hundred percent of participants experienced resolution of their constipation during the soy milk condition compared with 68% experiencing resolution during the soy milk condition in the Iacono and colleagues study (n=65). Thirteen participants were recruited to Trial 1. Nine participants returned constipation diaries for the study period. The mean (SD) number of stools for each of the conditions was: baseline, 5.1 (1.4); cow’s milk 9.9 (4.4); washout 13.0 (5.2); and soy milk 15.1 (5.0). The differences between the three dietary conditions were statistically significant, p=0.03. The results confirmed the hypothesis that children in the Australian setting with chronic functional constipation unresponsive to the usual treatments, respond to the removal of cow’s milk protein from the diet. Chapter 5 describes the results of Trial 2, the double blind crossover trial comparing the effects of cow’s milk β-casein A1 and cow’s milk β-casein A2 in children with chronic functional constipation. Thirty-nine participants were recruited to Trial 2 and 26 participants returned constipation diaries for the trial period. Unlike the soy result, the cow’s milk β casein A2 did not give 100% resolution of constipation, in fact, the percentage resolution was almost identical to the cow’s milk β casein A1 result. The fact that some children responded during the cow’s milk casein A1 condition in both trials could be caused by a threshold effect, given it was likely that participants were consuming less cow’s milk protein during the trial (400 mL with elimination of all other sources of cow’s milk protein) than on their pre-trial diet. Resolution with both the cow’s milk β casein A1 and cow’s milk β casein A2 conditions suggests that these children are able to tolerate some cow’s milk protein before the symptom of constipation occurs. This could be a food intolerance type reaction or there is some other component in cow’s milk that is causing the problem in these children. Chapter 6 describes a qualitative study of the feasibility for mothers to administer a cow’s milk protein free diet to their children. The experiences of mothers following a cow’s milk protein free diet to assist in the management of chronic functional constipation in children were reported. A number of themes were identified that are useful to health professionals educating families. Mothers found the removal of cow’s milk protein from the diets of their children challenging but persevered due to the potential benefit to their children. Many mothers planned to continue post study with a modified approach to the cow’s milk protein free diet by allowing some cow’s milk protein in the diet to make the diet more acceptable to the family but not as much as the pre-trial diet. These experiences provide health professionals with valuable insights and ideas to assist their patients to manage a cow’s milk protein free diet. Chapter 7 discusses all aspects of the research including any limitations. The results of Trial 1 confirmed the hypothesis that children in the Australian settling with chronic functional constipation unresponsive to the usual treatments respond to the removal of cow’s milk protein from the diet. Therefore, cow’s milk protein is involved in the aetiology of constipation in these children. All the study participants demonstrated an absence or low level of normal gut flora, which may affect bowel regularity. Further research into species present and absent may provide further explanations to the lack of bowel regularity in these children. The immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein requires further investigation. Although the number of statistically significant variables between the conditions was low, there was a high degree of abnormality. Further investigations are needed, including research into food intolerance reactions that affect the nerve endings in the bowel. The results in Trial 1 and Trial 2 are suggestive of an involvement of blood factors including platelets and monocytes. Other children may have a chronic Streptococcus A infection which may be contributing to constipation as well as to liver function abnormalities. Liver function abnormalities were observed for some participants in both trials, independent of milk condition. The extent to which the research questions have been answered is evaluated in Chapter 7, which includes the conclusions and recommendations of this research. In brief, the findings were: • Children with chronic functional constipation that is unresponsive to the traditional treatments should trial a cow’s milk protein free diet for at least two weeks to determine whether this may resolve the constipation. During this period, the numbers and form of bowel motions should be recorded and results compared to a one week record collected prior to commencing the cow’s milk protein free diet. • Due to the complicated nature of a cow’s milk protein free diet, especially the number of processed foods which contain hidden cow’s milk protein, consultation with a dietitian is essential for implementation of this diet. The dietitian should consider educating the patient’s family, both parents and siblings, to ensure the best outcome in terms of acceptance and compliance of the diet, and provide adequate resources. • If this dietary modification is successful for the child and alleviates constipation, consultation with a dietitian is recommended to determine the amount tolerated and nutritional adequacy of the diet. Soy milk is recommended as a substitute for cow’s milk and a probiotic needs to be prescribed to assist with the normalisation of gut flora. • Education of health professionals such as general practitioners, paediatricians, and paediatric continence nurses, regarding a cow’s milk protein free diet for chronic functional constipation, is essential to support the child and his/her family and integral to the success of this strategy. The findings of this research will be published in the scientific literature and as conference presentations. It is hoped that these findings will assist in the management of children with chronic functional constipation unresponsive to the traditional treatments.

Orientador: Pedro Luiz Toledo de Arruda Lourenção / Resumo: Introdução: A Displasia Neuronal Intestinal tipo B (DNI-B) é uma entidade patológica caracterizada por anormalidades nos plexos nervosos submucosos do sistema nervoso entérico, comumente associada à constipação intestinal na infância. Os microRNAs (miRNAs) são pequenos RNAs não-codificantes com um papel importante na regulação da expressão gênica, e têm sido considerados potenciais biomarcadores diagnósticos em diversas doenças. Objetivo: Determinar o perfil de expressão global de miRNAs em amostras de plasma e tecido de biópsia retal de pacientes com DNI-B. Métodos: Cinqüenta pacientes, com idade entre 0 e 15 anos, diagnosticados com DNI-B entre 1998 a 2010, foram incluídos no estudo. Amostras de sangue periférico foram coletadas de todos os 50 pacientes e 10 crianças saudáveis, sem sintomas intestinais (grupo controle). Dos 50 pacientes dos quais o sangue foi coletado, 29 também apresentavam fragmentos embolcados de tecido retal suficiente para extração de RNA. Estes materiais foram processados por microdissecção e agrupados de acordo com as diferentes camadas da parede intestinal. A extração de miRNA foi realizada utilizando o kit miRNeasy Serum / Plasma e o kit de recuperação de todos os Nucleic Acid Isolation para tecidos de biópsia. A análise global da expressão de miRNA foi realizada utilizando a plataforma TaqMan Array Human MicroRNA Card A. Análise de correlação entre a expressão de miRNA em amostras de plasma e biópsia, bem como entre os tecidos derivados das camada... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Intestinal Neuronal Dysplasia type B (IND-B) is a pathological entity characterized by abnormalities in the submucous nerve plexuses of the enteric nervous system, commonly associated with intestinal constipation in childhood. microRNAs (miRNAs) are small non-coding RNAs with a potent role in gene expression regulation, and have been demonstrated as potential diagnostic biomarkers in several diseases. Objective: To determine the global expression profile of miRNAs in plasma and rectal biopsy tissue samples from patients with IND-B. Methods: Fifty patients, aged 0 to 15 years, who had been diagnosed with IND-B, from 1998 to 2010, were included in the study. Peripheral blood samples were collected from all 50 patients and an additional 10 healthy children, without intestinal symptoms (control group). Of the 50 patients from whom blood was collected, 29 also had sufficient rectal tissue for RNA extraction. Rectal biopsies were processed by microdissection and pooled according the different layers of the intestinal wall. miRNA extraction was performed using the miRNeasy Serum/Plasma Kit and the Recover All Total Nucleic Acid Isolation kit for biopsy tissues. Global miRNA expression analysis was performed using the TaqMan Array Human MicroRNA Card A platform. Correlation analysis between miRNA expression in plasma and biopsy samples as well as among tissues derived from the distinct intestinal layers was performed. Results: miRNA let-7a was over-expressed (~7 fold hi... (Complete abstract click electronic access below) / Doutor

Introdução: Diferentes critérios são apresentados na literatura para definir constipação, o que pode explicar a grande variabilidade de incidência desse desfecho. No Brasil, pouco se sabe sobre constipação e seus determinantes em adultos criticamente doentes. Objetivo: Avaliar a incidência e os fatores associados a constipação em adultos críticos. Método: De novembro de 2015 a setembro de 2016, foi conduzida uma coorte prospectiva de adultos que foram acompanhados desde a sua admissão no Centro de Tratamento Intensivo até sua saída. Os pacientes foram diariamente avaliados por uma equipe capacitada previamente quanto a variáveis clínicas, terapêutica instituída, características e frequência das evacuações. Constipação foi definida pela ausência de evacuação por três dias consecutivos. Para fins de análise, os dados foram censurados no décimo dia de internação. Após análise univariada, foi empregada Regressão Múltipla de Cox, na qual estabeleceu-se o número de dias até o primeiro episódio de evacuação como variável de tempo. Foi adotado método “enter” para o processamento do modelo, sendo removidas as variáveis, uma a uma, a partir do maior valor-p, durante a modelagem. O ajuste do modelo foi testado por meio do teste Omnibus. O projeto do presente estudo foi aprovado quanto aos seus aspectos éticos e metodológicos pelo Comitê de Ética da instituição sede do estudo. Resultados: Nos 157 pacientes acompanhados, a mediana de dias até a primeira evacuação foi de 4 (P25: 2 – P75: 6). A incidência de constipação foi de 75,8%. A análise univariada mostrou que pacientes constipados eram mais jovens, usaram mais sedação e apresentaram mais motivos respiratórios e pós-operatórios como causas para internação, enquanto pacientes não constipados internaram mais por motivos gastroenterológicos. O uso de drogas vasoativas, ventilação mecânica e hemodiálise foi semelhante entre constipados e não constipados. A análise multivariada, os dias de uso de docusato + bisacodil (HR: 0,79; IC95%: 0,65 – 0,96) de omeprazol ou ranitidina (HR: 0,80; IC95%: 0,73 – 0,88) e de lactulose (HR: 0,87; IC95%: 0,76 – 0,99) foram fatores independentes de proteção para constipação. Conclusão: Constipação é muito incidente em adultos críticos. Os dias de uso de medicamentos com ação no trato digestório (lactulose, docusato + bisacodil e omeprazol e/ou ranitidina) são capazes de prevenir esse desfecho. / Introduction: The literature present different criteria to define constipation, which may explain the great variability of its incidence. In Brazil, little is known about constipation and its determinants in critically ill adults. Objective: To evaluate the incidence and factors associated with constipation in critical adult patients. Method: From the November of 2015 to September 2016, a prospective cohort of critically ill adults was conducted. Patients were followed from their admission to the Intensive Care Unit until their discharge from the Intensive Care Unit or death. Trained team daily evaluated patients. Clinical variables, established therapy, characteristics and frequency of bowel movements were registered. Constipation was defined by absence of evacuation for three consecutive days. After univariate analysis, Cox Multiple Regression was used. In this analysis, the time variable was the number of days until the first evacuation episode. Enter method was used to the model processing, and the variables were removed one by one from the largest p-value during the statistical modeling. The Omnibus test was utilized to test the model adjustment. The study was approved by the ethics committee of the institution’s head office regarding its ethical and methodological aspects. Results: To the 157 patients followed up, the median number of days until the first evacuation was 4 (2 - 6). The incidence of constipation was 75.8%. Univariate analysis showed that constipated patients were younger, they used more sedation and presented more respiratory and postoperative reasons as causes for hospitalization, while non-constipated patients were more frequently admitted for gastroenterological reasons. The use of vasoactive drugs, mechanical ventilation and renal replacement therapy (hemodialysis) was similar in constipated and non-constipated patients. In Multivariate analysis the days of use of docusate + bisacodyl (HR0.79; CI95%: 0.65 – 0.96), omeprazole or ranitidine (HR: 0,80; CI95%: 0.73 – 0.88) and lactulose (HR: 0.87; CI95%: 0.76 – 0.99) were independent protective factors for constipation. Conclusion: Constipation has high incidence among critical adult patients. Days using drugs with a digestive tract action (lactulose, docusate + bisacodyl and omeprazole and / or ranitidine) are able to prevent this issue.

Introdução: A constipação funcional corresponde a aproximadamente 90 a 95% dos casos de constipação crônica infantil, sendo uma doença frequente e com grande impacto na qualidade de vida do paciente pediátrico e de sua família. O aumento do consumo de fibras na dieta está associado com estímulo da peristalse gastrointestinal, acelerando o trânsito colônico. Entretanto, ainda não existem evidências claras que corroborem o uso rotineiro da suplementação de fibras na dieta das crianças como parte do tratamento da constipação funcional. Objetivo: Reunir evidências atuais sobre o uso de fibras no tratamento da constipação em pacientes pediátricos. Métodos: Revisão sistemática com metanálise de estudos controlados randomizados identificados por meio de pesquisa nas bases de dados Pubmed, Embase, LILACS e Cochrane. Critérios de Inclusão: Estudos controlados randomizados; pacientes com idade entre 2 a 18 anos e com diagnóstico de constipação não orgânica em uso ou não de tratamento medicamentoso para constipação; artigos publicados em língua portuguesa, inglesa, espanhola, francesa e alemã; artigos documentados e/ou publicados em revistas acessíveis aos pesquisadores. Resultados: Foram encontrados 2.963 artigos na busca e, após avaliação adequada, 9 artigos mostraram-se relevantes frente aos objetivos do estudo. Um total de 680 crianças foram incluídas, sendo 45% meninos. Não foi demonstrado significância estatística da frequência evacuatória, da consistência evacuatória, do sucesso terapêutico, da incontinência fecal e da dor abdominal com o uso de fibras nos pacientes com constipação infantil. Esses resultados devem ser interpretados com atenção devido a alta heterogeneidade clínica entre os estudos e a limitação metodológica dos artigos selecionados para análise. Conclusão: Existe uma grande falta de estudos qualificados para avaliar a suplementação de fibras no tratamento da constipação infantil, gerando um baixo grau de confiança para se estimar o efeito real dessa intervenção na população em questão. Até esse momento, conforme a literatura atual, deve-se apenas recomendar a ingestão adequada de fibras (oriundas de alimento ou suplemento) conforme a idade para as crianças com constipação, não se devendo prescrever a suplementação de fibras como tratamento para crianças e adolescentes constipados. / Introduction: Functional constipation corresponds to approximately 90 to 95% of cases of chronic constipation in children, being a frequent disease with great impact on the quality of life of the pediatric patient and his family. Increase fiber dietary intake is associated with stimulation of gastrointestinal peristalsis, accelerating colonic transit. However, there is still no clear evidence to support the routine use of fiber supplementation in the diet of children as part of the treatment of functional constipation. Objective: To gather current evidence on the use of fiber in the treatment of constipation in pediatric patients. Methods: Systematic review with meta-analysis of randomized controlled trials identified through Pubmed, Embase, LILACS and Cochrane databases. Inclusion Criteria: Randomized controlled trials; Patients aged between 2 and 18 years and diagnosed with non-organic constipation in use or not of drug treatment for constipation; Articles published in Portuguese, English, Spanish, French and German; Articles published in journals accessible to the researchers. Results: A total of 2.963 articles were found in the search and, after adequate evaluation, 9 articles were relevant to the study objective. A total of 680 children were included, of which 45% were boys. No statistical significance was demonstrated for evacuation frequency, bowel consistency, therapeutic success, fecal incontinence, and abdominal pain with fiber in patients with childhood constipation. These results should be interpreted with caution due to the high clinical heterogeneity between the studies and the methodological limitation of the articles selected for analysis. Conclusion: There is a great lack of qualified studies to evaluate fiber supplementation in the treatment of childhood constipation, generating a low degree of confidence in estimating the real effect of this intervention in the population in question. According to the current literature, it is necessary to recommend the adequate intake of fibers (from food or supplement) according to age for children with constipation, and it is not advised to prescribe fiber supplementation as a treatment for constipated children and adolescents.

Background: Many children suffer from functional constipation. In case of functional constipation there is no underlying disease. In Sweden, functional constipation is very common in children. Risk factors include lack of physical activity, irregular toilet habits and insufficient intake of fibers and fluids. Child health nurse has the knowledge and skills to advise and treat children in functional constipation and to support and reduce the suffering. Aim: The aim of the study was to illuminate child health nurses' experiences in the care of children with functional constipation. Method: Ten child health nurses were interviewed during a semi structured interview used openended questions. The interviews were recorded as digital files and transcribed verbatim and then analyzed according to a qualitative content analysis. Results: The child health nurses described experiences in the care of children with functional constipation. There were two categories from the analyzed data: "to base on the child`s needs" and "the child´s physical and psychosocial environment". Conclusion: This study shows the child health nurses experiences in the care of children with functional constipation. The care is based on the childs neeeds and the environment around the child in terms of physical and psychosocial environment is taken into account. The child health nurses should be aware of the reason why parents seek care, how to find the cause of functional constipation and how to relieve the child's suffering. She creates a health promotion meeting with children and parents seeking care for functional constipation.

Introdução: Diferentes critérios são apresentados na literatura para definir constipação, o que pode explicar a grande variabilidade de incidência desse desfecho. No Brasil, pouco se sabe sobre constipação e seus determinantes em adultos criticamente doentes. Objetivo: Avaliar a incidência e os fatores associados a constipação em adultos críticos. Método: De novembro de 2015 a setembro de 2016, foi conduzida uma coorte prospectiva de adultos que foram acompanhados desde a sua admissão no Centro de Tratamento Intensivo até sua saída. Os pacientes foram diariamente avaliados por uma equipe capacitada previamente quanto a variáveis clínicas, terapêutica instituída, características e frequência das evacuações. Constipação foi definida pela ausência de evacuação por três dias consecutivos. Para fins de análise, os dados foram censurados no décimo dia de internação. Após análise univariada, foi empregada Regressão Múltipla de Cox, na qual estabeleceu-se o número de dias até o primeiro episódio de evacuação como variável de tempo. Foi adotado método “enter” para o processamento do modelo, sendo removidas as variáveis, uma a uma, a partir do maior valor-p, durante a modelagem. O ajuste do modelo foi testado por meio do teste Omnibus. O projeto do presente estudo foi aprovado quanto aos seus aspectos éticos e metodológicos pelo Comitê de Ética da instituição sede do estudo. Resultados: Nos 157 pacientes acompanhados, a mediana de dias até a primeira evacuação foi de 4 (P25: 2 – P75: 6). A incidência de constipação foi de 75,8%. A análise univariada mostrou que pacientes constipados eram mais jovens, usaram mais sedação e apresentaram mais motivos respiratórios e pós-operatórios como causas para internação, enquanto pacientes não constipados internaram mais por motivos gastroenterológicos. O uso de drogas vasoativas, ventilação mecânica e hemodiálise foi semelhante entre constipados e não constipados. A análise multivariada, os dias de uso de docusato + bisacodil (HR: 0,79; IC95%: 0,65 – 0,96) de omeprazol ou ranitidina (HR: 0,80; IC95%: 0,73 – 0,88) e de lactulose (HR: 0,87; IC95%: 0,76 – 0,99) foram fatores independentes de proteção para constipação. Conclusão: Constipação é muito incidente em adultos críticos. Os dias de uso de medicamentos com ação no trato digestório (lactulose, docusato + bisacodil e omeprazol e/ou ranitidina) são capazes de prevenir esse desfecho. / Introduction: The literature present different criteria to define constipation, which may explain the great variability of its incidence. In Brazil, little is known about constipation and its determinants in critically ill adults. Objective: To evaluate the incidence and factors associated with constipation in critical adult patients. Method: From the November of 2015 to September 2016, a prospective cohort of critically ill adults was conducted. Patients were followed from their admission to the Intensive Care Unit until their discharge from the Intensive Care Unit or death. Trained team daily evaluated patients. Clinical variables, established therapy, characteristics and frequency of bowel movements were registered. Constipation was defined by absence of evacuation for three consecutive days. After univariate analysis, Cox Multiple Regression was used. In this analysis, the time variable was the number of days until the first evacuation episode. Enter method was used to the model processing, and the variables were removed one by one from the largest p-value during the statistical modeling. The Omnibus test was utilized to test the model adjustment. The study was approved by the ethics committee of the institution’s head office regarding its ethical and methodological aspects. Results: To the 157 patients followed up, the median number of days until the first evacuation was 4 (2 - 6). The incidence of constipation was 75.8%. Univariate analysis showed that constipated patients were younger, they used more sedation and presented more respiratory and postoperative reasons as causes for hospitalization, while non-constipated patients were more frequently admitted for gastroenterological reasons. The use of vasoactive drugs, mechanical ventilation and renal replacement therapy (hemodialysis) was similar in constipated and non-constipated patients. In Multivariate analysis the days of use of docusate + bisacodyl (HR0.79; CI95%: 0.65 – 0.96), omeprazole or ranitidine (HR: 0,80; CI95%: 0.73 – 0.88) and lactulose (HR: 0.87; CI95%: 0.76 – 0.99) were independent protective factors for constipation. Conclusion: Constipation has high incidence among critical adult patients. Days using drugs with a digestive tract action (lactulose, docusate + bisacodyl and omeprazole and / or ranitidine) are able to prevent this issue.