RESUMO
Low bone mineral density (BMD) as a risk factor for fractures has been a long-standing concern in phenylketonuria (PKU). It is hypothesised that the disease itself or the dietary treatment might lead to a low BMD. Previous studies show conflicting results of BMD in PKU due to differences in age, techniques to assess BMD and criteria used. To assess the prevalence of low BMD and define possible risk factors in a large number of adult, early treated PKU (ETPKU) patients. European centres were invited for a survey, collecting retrospective data including results of dual-energy X-ray absorptiometry (DXA) scans of adult ETPKU patients. BMD of 183 adult ETPKU patients aged 18-46 (median age 28, all females premenopausal) years was lower than in the general population at most skeletal sites but the frequency of low BMD (Z-score <-2) was at maximum 5.5%. No risk factors for low BMD in PKU patients could be identified. Low BMD occurs only in a small subset of PKU patients. DXA scans should be considered for well controlled patients from age 35-40 years and up and on indication in those PKU patients considered to be at increased risk for fractures.
Assuntos
Densidade Óssea , Fenilcetonúrias/fisiopatologia , Absorciometria de Fóton , Adolescente , Adulto , Doenças Ósseas Metabólicas/diagnóstico , Europa (Continente) , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Familial hypobetalipoproteinaemia is a disorder of lipid metabolism characterized by low levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B. ApoB-related familial hypolipoproteinemia is an autosomal condition with a codominance inheritance pattern. Non-classical congenital adrenal hyperplasia is an autosomal recessive disorder due to mutations in the CYP21A2, a gene encoding for the enzyme 21-hydroxylase, which results in an androgen excess production from adrenal source. We here present the case of a 25-year-old woman with NCAH showing decreased levels of total-cholesterol, low-density lipoprotein cholesterol and triglycerides. Her parent had digestive symptoms and severe hepatic steatosis with elevated liver enzymes, as well as decreased levels of total and low-density lipoprotein cholesterol. A genetic-molecular study of the proband identified a mutation in the APOB gene, which allowed a diagnosis of heterozygous ApoB-related hypolipoproteinaemia to be made.
Assuntos
Hiperplasia Suprarrenal Congênita , Apolipoproteínas B , LDL-Colesterol , Hipobetalipoproteinemia Familiar por Apolipoproteína B , Mutação , Humanos , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/complicações , Feminino , Adulto , Hipobetalipoproteinemia Familiar por Apolipoproteína B/genética , Apolipoproteínas B/genética , LDL-Colesterol/sangue , Colesterol/sangue , Triglicerídeos/sangue , Esteroide 21-Hidroxilase/genética , Heterozigoto , Fígado Gorduroso/genéticaRESUMO
Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for various significant medical conditions, yet controversy persists around its assessment and management. The diagnosis of disorders afffecting homocysteine (Hcy) metabolism faces delays due to insufficient awareness of its clinical presentation and unique biochemical characteristics. In cases of arterial or venous thrombotic vascular events, particularly with other comorbidities, it is crucial to consider moderate to severe HHcy. A nutritional approach to HHcy management involves implementing dietary strategies and targeted supplementation, emphasizing key nutrients like vitamin B6, B12, and folate that are crucial for Hcy conversion. Adequate intake of these vitamins, along with betaine supplementation, supports Hcy remethylation. Lifestyle modifications, such as smoking cessation and regular physical activity, complement the nutritional approach to enhance Hcy metabolism. For individuals with HHcy, maintaining a plasma Hcy concentration below 50 µmol/L consistently is vital to lowering the risk of vascular events. Collaboration with healthcare professionals and dietitians is essential for developing personalized dietary plans addressing the specific needs and underlying health conditions. This integrated approach aims to optimize metabolic processes and reduce the associated health risks.
Assuntos
Hiper-Homocisteinemia , Doenças Metabólicas , Adulto , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/terapia , Artérias , Vitaminas , Terapia ComportamentalRESUMO
We aimed to analyse the impact of COVID-19 during 2020 and 2021 on the prescription of enteral nutritional support and its expenditure in the Community of Madrid, Spain, compared to pre-pandemic data from 2016 in the general population vs. elderly. We analysed official electronic prescriptions of all public hospitals of the Community of Madrid. The population over 75 years of age have the higher prescription of nutritional supplements (p < 0.001 vs. other age groups), with no differences between the 45−64 age group compared to the 65−74 age group (χ2 = 3.259, p = 0.196). The first wave of COVID-19 or the first time there was a real awareness of the virus in Spain is similar in a way to the first peak of prescription of enteral nutrition in March 2020. The second peak of prescription was observed in the over 75 age group in July 2020, being more pronounced in December 2020 and March−April of the following year (F = 7.863, p = 0.041). The last peaks correspond to summer 2021 and autumn of the same year (p = 0.031year 2021 vs. 2020, p = 0.011year 2021 vs. 2019), where a relationship between increased prescription of enteral nutrition and COVID-19 cases is observed. High-protein and high-calorie dietary therapies were the most prescribed in patients with or without diabetes. All of this entailed higher cost for the Community of Madrid. In conclusion, COVID-19 significantly affected the prescription of nutritional support, especially in the population over 75 years of age.
Assuntos
COVID-19 , Nutrição Enteral , Idoso , COVID-19/epidemiologia , COVID-19/terapia , Ingestão de Energia , Humanos , Prescrições , Espanha/epidemiologiaRESUMO
Hyperammonaemia is a metabolic derangement that may cause severe neurological damage and even death due to cerebral oedema, further complicating the prognosis of its triggering disease. In small children it is a rare condition usually associated to inborn errors of the metabolism. As age rises, and especially in adults, it may be precipitated by heterogeneous causes such as liver disease, drugs, urinary infections, shock, or dehydration. In older patients, it is often overlooked, or its danger minimized. This protocol was drafted to provide an outline of the clinical measures required to normalise ammonia levels in patients of all ages, aiming to assist clinicians with no previous experience in its treatment. It is an updated protocol developed by a panel of experts after a review of recent publications. We point out the importance of frequent monitoring to assess the response to treatment, the nutritional measures that ensure not only protein restriction but adequate caloric intake and the need to avoid delays in the use of specific pharmacological therapies and, especially, extrarenal clearance measures. In this regard, we propose initiating haemodialysis when ammonia levels are >200−350 µmol/L in children up to 18 months of age and >150−200 µmol/L after that age.
Assuntos
Hiperamonemia , Hepatopatias , Adulto , Idoso , Amônia/metabolismo , Criança , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/etiologia , Hiperamonemia/terapia , Hepatopatias/complicações , Prognóstico , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: Individual health education is considered to be essential in the overall care of patients with type 2 diabetes (DM2), although there is some uncertainty regarding its metabolic control benefits. There have been very few randomized studies on the effects of individual education on normal care in DM2 patients with a control group, and none of these have assessed the long-term results. Therefore, this study aims to use this design to assess the effectiveness of the PRECEDE (Predisposing, Reinforcing, Enabling, Causes in Educational Diagnosis, and Evaluation) education model in the metabolic control and the reduction of cardiovascular risk factors, in patients with type 2 diabetes. METHODS: An open community effectiveness study was carried out in 8 urban community health centers in the North-East Madrid Urban Area (Spain). Six hundred patients with DM2 were randomized in two groups: PRECEDE or conventional model for health promotion education. The main outcome measures were glycated hemoglobin A1c, body mass index (BMI), blood pressure, lipids and control criteria during the 2-year follow-up period. RESULTS: Glycated hemoglobin A1c and systolic blood pressure (SBP) levels decreased significantly in the PRECEDE group (multivariate analysis of covariance, with baseline glycated hemoglobin A1c, SBP, and variables showing statistically significant differences between groups at baseline visits). The decrease levels in diastolic blood pressure (DBP), triglycerides and LDL cholesterol were nonsignificant. PRECEDE increased compliance in all control criteria, except for LDL cholesterol. BMI did not change during the study in either of the two models analyzed. CONCLUSIONS: PRECEDE health education model is a useful method in the overall treatment in patients with type 2 diabetes, which contributes to decrease glycated hemoglobin A1c and SBP levels and increase the compliance in all the control criteria, except for LDL cholesterol. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01316367.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Conhecimentos, Atitudes e Prática em Saúde , Lipídeos/sangue , Modelos Teóricos , Educação de Pacientes como Assunto/métodos , Avaliação de Programas e Projetos de Saúde , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado , EspanhaRESUMO
Bariatric surgery is one of the most effective treatments currently available for obesity and its derived comorbidities. However, complications may occur, especially when malabsorptive surgeries like a biliopancreatic diversion is performed. We present the case of a female patient whose obesity was treated with this technique, and in the 9th year of follow-up developed an extensive dermatitis secondary to zinc deficiency and malnutrition, precipitated by therapeutic non-compliance. A close surveillance of early symptoms and signs of nutritional deficiencies as well as chronic supplementation of vitamins and trace elements is required; this case illustrates the relevance of periodical, lifelong visits to a medical physician with special training and experience in the management of post bariatric surgery patients in order to prevent, diagnosis and early treat related complications.
Assuntos
Deficiência de Vitaminas/etiologia , Cirurgia Bariátrica/efeitos adversos , Dermatite/etiologia , Desnutrição/etiologia , Zinco/deficiência , Adulto , Feminino , Humanos , Obesidade Mórbida/cirurgiaRESUMO
INTRODUCTION: Objectives: the aim of the study was to analyze the impact of COVID-19 on enteral nutrition prescription in the Community of Madrid during the first semester of 2020. Material and Methods: this is a descriptive study of enteral nutrition prescription in the first semester of 2020 and its comparison with the first semester of 2019. We included all the prescriptions in public hospitals of the Community of Madrid as recorded in public electronic databases. Results: there was an 8 % increase in the number of enteral nutrition prescriptions in March 2020 when compared with the previous months (p < 0.001). Then, in April and May 2020 we observed a 9 % decrease in enteral nutrition prescriptions (p < 0.001). Total costs in enteral nutrition showed a similar pattern, with an increase in March 2020 (p < 0.001) and a decrease in April and May 2020 (p < 0.001). When analyzing the data by patient age, those above 75 y.o. showed the highest decrease in enteral nutrition prescriptions (33.1 % higher than for those under 75 y.o.) in April and May 2020 (p < 0.001). Conclusions: the irruption of COVID-19 had a relevant impact on enteral nutrition prescription, especially among the elderly. Follow-up is needed to assess the long-term consequences of this in nutritional therapy.
INTRODUCCIÓN: Objetivos: el objetivo de este estudio es analizar el impacto de la COVID-19 en el primer semestre del año 2020, con respecto a la prescripción de soportes nutricionales enterales, y su gasto en la Comunidad de Madrid. Material y métodos: estudio descriptivo y comparativo del consumo de productos de nutrición enteral prescritos en recetas oficiales electrónicas durante el primer semestre de los años 2019 y 2020 en los hospitales públicos de la Comunidad de Madrid. Resultados: al analizar la prescripción del número de envases totales durante el periodo estudiado, por meses, se observa un incremento del 8 % en la prescripción durante el mes de marzo, comparado con los meses previos (p < 0,001), seguido de un descenso del 9 % en los meses de abril y mayo (p < 0,001). El comportamiento de la evolución del gasto sigue el mismo patrón, con un incremento en el mes de marzo (p < 0.001) y un descenso en los meses de abril y mayo de similar magnitud (ambos, p < 0,001). Al analizar por grupos de edades, el grupo de edad de más de 75 años fue el grupo con la mayor caída en las prescripciones (33,1 % mayor que entre los menores de 75) en los meses de abril y mayo de 2020 (p < 0,001). Conclusiones: la COVID-19 afectó de forma importante a la prescripción del soporte nutricional, especialmente en el grupo de mayor edad. El seguimiento de la enfermedad nos permitirá profundizar en el papel de la nutrición a corto y largo plazo.
Assuntos
COVID-19/epidemiologia , Prescrição Eletrônica/estatística & dados numéricos , Nutrição Enteral/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Nutrição Enteral/tendências , Humanos , Espanha/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
Background. Multiple acyl-CoA dehydrogenase deficiency is an autosomal recessive disorder of the amino acid metabolism and fatty acid oxidation due to the deficiency of the electron transfer protein or electron transfer protein ubiquinone oxidoreductase. The clinical picture ranges from a severe neonatal lethal presentation to late myopathic forms responsive to riboflavin. Up to now, there is no effective treatment for the neonatal form, which exhibits severe metabolic acidosis, hyperammonemia, hypoketotic hypoglycemia, and rhabdomyolysis. We present the case of a child who has had a good long-term outcome after a typical neonatal onset, with a dramatic drop in ammonia levels during the initial metabolic decompensation crisis and adequate control even during intercurrent diseases thereafter with N-carbamylglutamate treatment.
RESUMO
OBJECTIVE: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. METHODS: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. RESULTS: Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. CONCLUSIONS: Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications.
Assuntos
Diabetes Autoimune Latente em Adultos/metabolismo , Adulto , Idade de Início , Autoanticorpos/sangue , Autoantígenos/imunologia , Glicemia/análise , Pressão Sanguínea , Peptídeo C/análise , Estudos Transversais , Complicações do Diabetes/epidemiologia , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Insulina/uso terapêutico , Diabetes Autoimune Latente em Adultos/tratamento farmacológico , Diabetes Autoimune Latente em Adultos/imunologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
The use of home parenteral nutrition (HPN) in patients who can not obtain their nutritional requirements by the enteral route is increasing in recent years, allowing normalization lifestyle of patients. Neoplasm and mesenteric ischaemia are some of the diseases that most frequently require HPN in Spain. However, HPN is one of the cornerstones of the treatment of much less frequent illnesses as in the case of encapsulating peritoneal sclerosis. We present the case of a patient with encapsulating peritoneal sclerosis and HPN support for more than 7 years with a peripherally inserted central catheter (PICC) for over 6 years without complications and the autonomy to perform his normal business activity. Given the exceptional nature of the case we refer it to its publication.
El uso de la nutrición parenteral domiciliaria (NPD) en pacientes que no pueden alcanzar sus requerimientos nutricionales por la vía enteral está aumentando en los últimos años, permitiendo la normalización del estilo de vida de los pacientes. Entre las patologías que más frecuentemente precisan de la NPD en España destacan la neoplasia y la isquemia mesentérica. Sin embargo, la NPD constituye uno de los pilares básicos del tratamiento de enfermedades mucho menos frecuentes como es el caso de la esclerosis peritoneal encapsulante. A continuación presentamos el caso de un paciente diagnosticado de esclerosis peritoneal encapsulante con soporte NPD de más de 7 años de NPD con un catéter central de inserción periférica (PICC) para la NPD sin complicaciones y pudiendo realizar su actividad laboral habitual. Dado lo excepcional del caso lo remitimos para su publicación.
Assuntos
Cateterismo Venoso Central/métodos , Nutrição Parenteral no Domicílio , Fibrose Peritoneal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Peritoneal/diagnóstico por imagem , Autonomia Pessoal , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To assess the validity and concordance of diabetes data in the electronic health records of primary care (Madrid-PC) by comparing with those from the PREDIMERC study. METHODS: The sensitivity, specificity, positive predictive value, negative predictive value and kappa index of diabetes cases recorded in the health records of Madrid-PC were calculated by using data from PREDIMERC as the gold standard. The prevalence of diabetes was also determined according to each data source. RESULTS: The sensitivity of diabetes recorded in Madrid-PC was 74%, the specificity was 98.8%, the positive predictive value was 87.9%, the negative predictive value was 97.3%, and the kappa index was 0.78. The prevalence of diabetes recorded in Madrid-PC was 6.7% versus 8.1% by PREDIMERC, where known diabetes was 6.3%. CONCLUSIONS: The electronic health records of primary care are a valid source for epidemiological surveillance of diabetes in Madrid.
Assuntos
Diabetes Mellitus , Registros Eletrônicos de Saúde/estatística & dados numéricos , Atenção Primária à Saúde , Estudos Transversais , Diabetes Mellitus/epidemiologia , Monitoramento Epidemiológico , Humanos , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study. DESIGN: The MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain). RESULTS: The cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04-9.22) and the incidence density was 2.03 (95% CI = 1.75-2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10-2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39-18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18-3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30-2.77), and aspirin use (HR = 1.65; 95% CI = 1.22-2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75-1.82) and being female (HR = 1.12; 95% CI = 0.84-1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use. CONCLUSIONS: After a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of cardiovascular events. However, further studies with patients at high cardiovascular and metabolic risk are needed to clarify this issue.
Assuntos
Retinopatia Diabética/epidemiologia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco , Espanha/epidemiologiaRESUMO
BACKGROUND: Hypertension (HT) is a major modifiable cardiovascular risk factors. The objective of this study is to estimate the adult population of the Community of Madrid (30-74 years) prevalence of hypertension, knowledge, degree of control and drug treatment. METHODS: We studied a random sample population in 2007 among residents of Madrid Community of between 30 and 74 years, obtained by cluster sampling. An epidemiological questionnaire was applied through telephone interview. Physical examination was conducted by a team of trained nurses in the health center. To assess control of hypertension by number of active ingredients odds were calculated through logistic regression models. RESULTS: The final sample included 1,085 men and 1,183 women with a mean age of 48.3 years. The prevalence of hypertension was 29.3% (35.1% men and 23.9% in women (p<0.01). Of the 665 hypertensives identified 68.6% knew their condition (62.4 76.65% in males and females, p<0.05), of which 54% were in drug treatment (45.4% in men and 64.5% in women, p<0.05). Of the 265 treated hypertensive patients, blood pressure was controlled in 33% of males and 49% of women, p<0.05. Patients treated with two or more active improves your control (aOR: 1, 89). CONCLUSIONS: Our data on prevalence, treatment and control are at the lower-intermediate between those reported in previous studies on Spanish and European populations. However, the HA is a public health problem in the CM. Many hypertensive patients are not detected. Of those detected, only 1 in 3 of men and 1 in 2 women are well controlled.
Assuntos
Hipertensão/epidemiologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos Epidemiológicos , Humanos , Hipertensão/tratamento farmacológico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI), and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes. METHODS: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. (125)I-insulin binding and U-[(14)C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject. RESULTS: The duration of disease was negatively correlated with both (125)I-insulin binding capacity (r = -0.70, P < 0.05) and basal and maximum insulin-stimulated glucose transport (r = -0.87, P < 0.01, and r = -0.88, P < 0.01, respectively). Maximum specific (125)I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01). Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01). No correlation was found between BMI and insulin action. CONCLUSION: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a decrease in insulin action in these patients, and involving both receptor and postreceptor mechanisms.