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BACKGROUND: Prader-Willi syndrome (PWS) is suspected at birth if extreme hypotonia, difficulty in feeding, hypogonadism, and failure to thrive are present. Genetic diagnosis of PWS can generally be made within the first few months of life; however, a delayed diagnosis of PWS is frequently reported. Although the clinical characteristics of perinatal and neonatal patients with PWS have been reported, there are no such reports on the clinical characteristics of these patients in Japan. METHODS: This retrospective, single-center study involved 177 Japanese patients with PWS and their medical data regarding the perinatal and neonatal periods were evaluated. RESULTS: The median maternal age at birth was 34 years; 12.7% of the mothers had a history of assisted reproductive technology (ART). Of the mothers, 13.5% reported polyhydramnios and 4.3% had oligohydramnios. Decreased fetal movement during pregnancy was reported by 76% of the mothers. A total of 60.5% of patients were born by cesarean section. Genetic subtypes included deletions (66.1%), uniparental disomy (31.0%), imprinting defects (0.6%), and other or unknown subtypes (2.3%). The median birth length was 47.5 cm and the median birthweight was 2476 g. Of the 160 patients, 14 (8.8%) were classified as small for gestational age. Most patients had hypotonia (98.8%), and 89.3% required gavage feeding at birth. Breathing problems, congenital heart disease, and undescended testis were noted in 33.1%, 7.0%, and 93.5% of patients, respectively. CONCLUSION: In our study, higher rates of ART, polyhydramnios, decreased fetal movements, cesarean section, hypotonia, feeding difficulties, and undescended testis were observed in PWS.
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Criptorquidismo , Poli-Hidrâmnios , Síndrome de Prader-Willi , Recém-Nascido , Masculino , Humanos , Gravidez , Feminino , Adulto , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/epidemiologia , Síndrome de Prader-Willi/genética , Hipotonia Muscular , Cesárea , Japão/epidemiologia , Estudos RetrospectivosRESUMO
It is unclear whether hypothyroidism is present in patients with Prader-Willi syndrome (PWS). This study aimed to clarify the state of the hypothalamic-pituitary-thyroid axis and the effects of growth hormone (GH) treatment on thyroid function in pediatric patients with PWS. We retrospectively evaluated thyroid function in 51 patients with PWS before GH treatment using a thyroid-releasing hormone (TRH) stimulation test (29 males and 22 females; median age, 22 months). We also evaluated the effect of GH therapy on thyroid function by comparing serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels at baseline, 1 year, and 2 years after GH therapy. TSH, fT4, and fT3 levels were 2.28 µU/ml (interquartile range [IQR]; 1.19-3.61), 1.18 ng/dl (IQR; 1.02-1.24), and 4.02 pg/dl (IQR; 3.54-4.40) at baseline, respectively. In 49 of 51 patients, the TSH response to TRH administration showed a physiologically normal pattern; in two patients (4.0%), the pattern suggested hypothalamic hypothyroidism (delayed and prolonged TSH peak after TRH administration). TSH, fT4, and fT3 levels did not change significantly during 1 or 2 years after GH treatment. The TSH response to TRH showed a normal pattern in most patients, and thyroid function did not change significantly during the 2 years after initiating GH treatment.
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Síndrome de Prader-Willi/tratamento farmacológico , Glândula Tireoide/fisiologia , Hormônios Tireóideos/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Síndrome de Prader-Willi/patologia , Prognóstico , Estudos Retrospectivos , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacosRESUMO
Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 µg/dl (IQR, 14.2-23.7 µg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 µg/dl), with a median peak of 41.5 µg/dl (IQR, 32.3-48.6 µg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 µg/dl), and 27.8 µg/dl (IQR, 23.7-30.5 µg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis.
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Hidrocortisona/sangue , Insulina/farmacologia , Síndrome de Prader-Willi/fisiopatologia , Hormônio Adrenocorticotrópico/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lactente , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiopatologia , Síndrome de Prader-Willi/tratamento farmacológico , Valores de ReferênciaRESUMO
BACKGROUND: Bloodstream infections (BSIs) represent one of the most severe and clinically important conditions in the hospital setting. We have organized an interdisciplinary antimicrobial stewardship team (AST) at our hospital and performed consultations focusing on BSI patients since 2013. This study aimed to evaluate the impact of AST interventions on the diagnosis, treatment, and clinical outcomes of BSI patients. METHODS: We conducted a retrospective quasi-experimental study of BSI patients at a single Japanese university hospital. AST provided recommendations to attending physicians regarding appropriate diagnosis, therapy, and management of BSI patients after reviewing medical charts. RESULTS: We identified a total of 308 cases of BSI from January to December, 2012 (pre-intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post-intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post-intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002). CONCLUSIONS: An interdisciplinary AST intervention approach decreases the use of inappropriate therapy and may improve clinical outcomes in BSI patients.
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Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Idoso , Bacteriemia/mortalidade , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/mortalidade , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Feminino , Mortalidade Hospitalar , Hospitais Universitários , Humanos , Masculino , Estudos RetrospectivosRESUMO
Long-term treatment with growth hormone (GH) in patients with Prader-Willi syndrome (PWS) improves not only height velocity, height standard deviation score, and final height, but also the degree of obesity and body composition abnormalities. Anecdotally, PWS patients tend to suffer from severe obesity and its complications after cessation of GH therapy. However, there have been no studies to investigate changes in body mass index (BMI) and adipose tissue distribution after cessation of GH therapy in young PWS patients. Therefore, we investigated changes in the BMI-standard deviation score (SDS) and adipose tissue distribution after cessation of GH therapy in PWS patients. We evaluated 14 PWS patients. BMI-SDS was calculated at 0, 6, 12, 18, and 24 months before and after cessation of GH treatment. We also evaluated subcutaneous adipose tissue (SAT) (cm(2)) and visceral adipose tissue (VAT) (cm(2)) area in 8 of the 14 study patients with single slice abdominal computed tomography at the level of the umbilicus. The BMI-SDS significantly increased at 6, 12, 18, and 24 months after cessation of GH therapy (P = 0.039, P = 0.008, P = 0.003, P = 0.003, respectively). There was a tendency toward increases in VAT at 12 and 24 months after cessation of GH therapy, but the increases did not reach statistical significance (P = 0.062, P = 0.125, respectively). Therefore, cessation of GH therapy in PWS patients worsened BMI. To maintain good body composition and prevent complications of obesity, long-term use of GH in adult PWS patients may be advisable.
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Índice de Massa Corporal , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Obesidade/etiologia , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/tratamento farmacológico , Suspensão de Tratamento , Adiposidade , Pesos e Medidas Corporais , Feminino , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Masculino , Síndrome de Prader-Willi/genética , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVES: Hypophosphatasia (HPP) is a rare skeletal dysplasia caused by variants in the alkaline phosphatase (ALPL) gene. More than 400 pathogenic variants of the ALPL gene have been registered in the ALPL gene variant database. Here, we describe the case of a Japanese child with odonto-hypophsphatasia (odonto-HPP) and a novel ALPL variant. CASE PRESENTATION: At the age of 2 years and 1 month, he prematurely lost one deciduous tooth, with the root intact, when he fell and hit his face lightly. Three months later, he lost another adjacent deciduous tooth without incentive. His serum alkaline phosphatase (ALP) level was 72â¯U/L. His urine phosphoethanolamine (PEA) level was extremely high at 938⯵mol/mg·Cre. The serum pyridoxal 5'-phosphaye (PLP) level was 255.9â¯nmol/L. Based on the clinical symptoms and laboratory findings, the patient was clinically diagnosed with odonto-HPP. Genetic analysis of the ALPL gene revealed a heterozygous variant (NM_000478.6:c.1151C>A, p.Thr384Lys). CONCLUSIONS: We report a case of odonto-HPP with a novel variant in the ALPL gene. HPP is a rare disease, and the heterozygous mutation in the ALPL gene highlights the novelty of this case.
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Hipofosfatasia , Masculino , Criança , Humanos , Pré-Escolar , Hipofosfatasia/genética , Hipofosfatasia/diagnóstico , Fosfatase Alcalina , Mutação , HeterozigotoRESUMO
Prader-Willi syndrome (PWS), a complex genetic disorder, arises from suppressed expression of paternally inherited imprinted genes on chromosome 15q11-q13. Characteristics include short stature, intellectual disability, behavioral problems, hypogonadism, obesity, and reduced bone and muscle mass. Testosterone replacement (TR) remains controversial due to concerns regarding behavioral problems. To evaluate the effects of TR on secondary sexual characteristics, body composition, and behavior in adult males with PWS, 22 male PWS patients over the age of 16 with behavioral scores of less than grade 4 on the Modified Overt Aggression Scale (MOAS) underwent monthly intramuscular TR (125 mg). Pubertal change, body composition and behavior were evaluated before and after 24 months of therapy. Serum testosterone, LH, and FSH did not change. Increased pubic hair was observed in 16 of 22 patients (72.7%). Percent body fat decreased from 47.55 ± 2.06% to 39.75 ± 1.60% (n = 18) (P = 0.018). Bone mineral density increased from 0.8505 ± 0.0426 g/cm(2) to 0.9035 ± 0.0465 g/cm(2) (n = 18) (P = 0.036), and lean body mass increased from 18093.4 ± 863.0 g to 20312.1 ± 1027.2 g (n = 18) (P = 0.009). The MOAS was unchanged, from 4.5 ± 2.0 at the beginning of the study to 3.0 ± 1.7 at the end of study indicating no increase in aggression. No behavioral problems were observed. Based on this pilot study, TR with 125 mg monthly is a potentially safe and useful intervention for adult males with PWS.
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Comportamento/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Terapia de Reposição Hormonal , Síndrome de Prader-Willi/tratamento farmacológico , Maturidade Sexual/efeitos dos fármacos , Testosterona/farmacologia , Testosterona/uso terapêutico , Adolescente , Adulto , Índice de Massa Corporal , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Prader-Willi/sangue , Resultado do Tratamento , Adulto JovemRESUMO
Marked anthropometric changes are seen in Prader-Willi syndrome (PWS). Emaciation is observed during infancy, whereas severe obesity is found in older children and adults. Growth hormone (GH) treatment modifies the anthropometric changes in PWS patients. In this study, we examined changes in the body composition of 51 PWS patients (age range, 6-54 years; median, 16.5 years), with a focus on the amount of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), VAT/SAT ratio, and serum levels of adipocytokines (adiponectin, leptin, and resistin). The relationships between VAT, SAT, and adipocytokines, and lipid abnormalities and type 2 diabetes in 24 patients with obese PWS were also evaluated. With increasing age, SAT and VAT both increased markedly, but in 18 patients receiving GH treatment, VAT remained low at ≤30 cm(2) . In the GH-completed patients (n = 19), VAT and SAT increased with age to levels similar to those in non-GH-treated patients (n = 14). In the obese group, adiponectin decreased as VAT increased (r = -0.35, P = 0.11). Leptin (r = 0.67, P < 0.001) and resistin (r = 0.45, P = 0.04) showed positive correlations with SAT. Total cholesterol, low-density lipoprotein, and triglyceride levels correlated negatively with adiponectin (r = -0.59, r = -0.56, r = -0.56, respectively, P < 0.05) and hemoglobin A1c (r = -0.42, P = 0.08). To maintain lower VAT and prevent cardiovascular disease risk factors, GH treatment may be advisable even in adult patients with PWS.
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Adiponectina/sangue , Distribuição da Gordura Corporal , Hormônio do Crescimento Humano/uso terapêutico , Leptina/sangue , Síndrome de Prader-Willi/tratamento farmacológico , Síndrome de Prader-Willi/genética , Resistina/sangue , Adolescente , Adulto , Antropometria , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Criança , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobinas Glicadas/genética , Hemoglobinas Glicadas/metabolismo , Humanos , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/fisiopatologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Síndrome de Prader-Willi/fisiopatologia , Estudos Retrospectivos , Gordura Subcutânea/metabolismo , Triglicerídeos/sangue , Adulto JovemRESUMO
The negative effects of anticoagulants are well-known in patients with renal impairment, drug-drug interaction, lower physical conditions, and multiple comorbidities. We highlight that even in patients with controllable multiple risks for rivaroxaban use, add-on inevitable risks will lead to negative effects greater than those expected.
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We present a case of chemotherapy-induced hiccups that were alleviated by steroid rotation. Hiccups are often overlooked, but they have an impact on the patient's quality of life. In the COVID-19 era, web-based teleworking has become an important tool, hiccups during a teleconference should be noted as a concern for patients.
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Growth hormone (GH) therapy is now widely given to Prader-Willi syndrome (PWS) patients to encourage growth in body height and to prevent obesity. Scoliosis, one of the complications in this syndrome, is thought to be accelerated in parallel with a rapid increase in body height, especially during adolescence. To determine whether GH therapy aggravates scoliosis and to identify any factor which might predict the progression of scoliosis, we studied 35 (22 males and 13 female) PWS patients between the ages of 2-16 years on GH therapy whose scoliosis was followed with spinal X-rays every 6 months. Thirteen (37.1%) of 35 patients had scoliosis with a Cobb angle of over 10°. Scoliosis was unchanged in five patients (14.3%), became worse in six (17.1%) and improved in two (5.7%). All 22 (62.9%) of 35 patients who did not have scoliosis did not develop scoliosis with GH therapy. Since abnormal paraspinal muscle development was thought to induce scoliosis, we measured cross-sectional areas of paraspinal muscles by using one slice CT scan at the level of the umbilicus at the level of L4. Since there was a delay in the increase in total paravertebral muscle area and prolonged asymmetry in patients with progressive scoliosis, both were thought to be useful predictors of progressive scoliosis in PWS patients with GH therapy.
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Hormônio do Crescimento Humano/uso terapêutico , Músculo Esquelético/diagnóstico por imagem , Síndrome de Prader-Willi/complicações , Escoliose/diagnóstico por imagem , Escoliose/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Tamanho do Órgão , Síndrome de Prader-Willi/tratamento farmacológico , Prognóstico , Escoliose/etiologia , Tomografia Computadorizada por Raios XRESUMO
There have been multiple reports regarding the growth hormone (GH) secretion in patients with Prader-Willi syndrome (PWS). However, none have compared GH secretion in children with deletion group to those with maternal uniparental disomy (UPD). We evaluated the GH secretion in pediatric patients with PWS. Seventy-six patients with a deletion (n = 55) or UPD (n = 21) were studied. The secretion of GH by insulin stimulation in the patients with UPD (3.6 ± 2.2 ng/ml) was significantly lower than those with deletions (peak GH level: 11.1 ± 8.6 ng/ml; P = 0.0013). We also compared the response to GH replacement therapy. Yearly improvements in height standard deviation score (SDS) were similar in the two groups (first year SDS: 0.47 ± 0.47, deletion; 0.68 ± 0.26, UPD; P = 0.14).
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Estatura , Genótipo , Hormônio do Crescimento/metabolismo , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , Adolescente , Criança , Pré-Escolar , Deleção Cromossômica , Feminino , Hormônio do Crescimento/uso terapêutico , Terapia de Reposição Hormonal , Humanos , Lactente , Masculino , Síndrome de Prader-Willi/tratamento farmacológico , Resultado do Tratamento , Dissomia UniparentalRESUMO
OBJECTIVES: A recent large retrospective cohort study of cases of hyponatremia in Prader-Willi syndrome (PWS), conducted at nine reference centers, showed that severe hyponatremia was rare in PWS (0.5%); furthermore, all cases involved adults. Here, we describe three pediatric cases of severe hyponatremia in PWS, with neurological symptoms. CASE PRESENTATION: The cases involved two girls and one boy, and only one patient showed uniparental disomy. All patients had hyponatremia during infancy and presented with clinical symptoms, such as convulsions. All three patients improved with intravenous fluids and fluid restriction, with no sequelae. CONCLUSIONS: We report three pediatric cases of symptomatic hyponatremia of unknown cause in PWS. In patients with PWS, especially those with neurological symptoms such as convulsions, it is necessary to take hyponatremia into consideration.
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Hiponatremia , Síndrome de Prader-Willi , Adulto , Criança , Feminino , Humanos , Hiponatremia/complicações , Masculino , Síndrome de Prader-Willi/complicações , Estudos Retrospectivos , Convulsões/complicações , Dissomia UniparentalRESUMO
OBJECTIVES: In recent years, research on behavioral and psychiatric problems of adults with Prader-Willi syndrome (PWS) has gained attention. However, no report is available regarding the relationship between psychiatric illness and type 2 diabetes mellitus (T2DM) in patients with PWS. Therefore, we evaluated a behavioral assessment to address the lack of data on the association between psychiatric behavior and T2DM. METHODS: This was a retrospective single-center study of patients with PWS. Patients with PWS whose blood tests were performed in our hospital between January 2018 and December 2019 and aged >10 years were included. We evaluated the data, including the behavioral patterns of Japanese PWS patients with T2DM. RESULTS: Overall, 114 patients were evaluated; 33 patients (28.9%) developed T2DM. The age of T2DM onset was 18.0 years (interquartile range [IQR], 14.6-21.4 years). The median body mass index at T2DM onset was 33.7 kg/m2 (IQR, 30.0-37.4 kg/m2). Between-group comparisons of the intelligence quotient, Food-Related Problem Questionnaire (FRPQ), and Japanese versions of the Short Sensory Profile and Aberrant Behavior Checklist showed a significant difference only in FRPQ scores (p=0.003). CONCLUSIONS: The occurrence of T2DM among Japanese patients with PWS remains high. Only the FRPQ was significantly different between the T2DM and the non-T2DM group.
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Diabetes Mellitus Tipo 2/epidemiologia , Síndrome de Prader-Willi/psicologia , Adolescente , Adulto , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hormônio do Crescimento/uso terapêutico , Humanos , Testes de Inteligência , Masculino , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/tratamento farmacológico , Estudos Retrospectivos , Caracteres Sexuais , Inquéritos e Questionários , Adulto JovemRESUMO
The relationship between sensory processing and ASD-like and associated behaviors in patients with Prader-Willi Syndrome (PWS) remains relatively unexplored. Examining this relationship, 51 adults with PWS were administered the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), Short Sensory Profile (SSP-J), Food-Related Problem Questionnaire (FRPQ), and Aberrant Behavior Checklist (ABC-J). Based on SSP-J z-scores, participants were classified into three severity groups. Analysis of variance was performed to compare the behavioral scores of these three groups. Statistically significant group differences were observed in PARS (p = .006, ηp2 = .194) and ABC-J (p = .006, ηp2 = .193) scores. Our findings suggest that the level of sensory processing may predict ASD-like and aberrant behaviors in adults with PWS, implying the importance of a proper assessment for early intervention.
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Transtorno do Espectro Autista , Transtorno Autístico , Síndrome de Prader-Willi , Adulto , Humanos , Percepção , Inquéritos e QuestionáriosRESUMO
The number of working-age individuals undergoing cancer treatment has been increasing. In these patients, transdermal fentanyl is the preferred treatment. However, it is known to have (1) pharmacodynamic interactions with benzodiazepines and (2) fever-induced pharmacokinetic variations. The aim of this study is to clarify the frequency of co-administration of benzodiazepine and the predictors for fever among working-age patients with cancer using transdermal fentanyl. We used a large claims data source including over 3.6 million patients. Finally, 759 working-age patients aged 20 to 60 years undergoing cancer treatment, in whom transdermal fentanyl was initiated, were analyzed. The proportion of patients receiving co-administration of benzodiazepines with the first administration of transdermal fentanyl was 16.5% (n = 125). This increased to 39.3% (n = 298) within 30 days. Predictive factors for fever using patients' baseline characteristics were male sex, gastrointestinal cancer, hematological cancer, and renal disease. To provide adequate pharmacotherapy to working-age patients undergoing cancer treatment with transdermal fentanyl, medical staff should pay attention to (1) avoid adding benzodiazepines easily and (2) monitor patients having predictors for fever to avoid fentanyl-related adverse events.
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Fentanila , Neoplasias , Administração Cutânea , Adulto , Analgésicos Opioides , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Dor/tratamento farmacológico , Prescrições , Adulto JovemRESUMO
OBJECTIVES: Previous reports indicate that growth hormone (GH) treatment for Prader-Willi syndrome (PWS) improves bone mineral density (BMD) only when initiated at a young age and not when initiated in adulthood. However, there are no data on BMD during long-term GH treatment of Japanese children and adolescents with PWS. Thus, this study aimed to investigate BMD changes among patients with PWS, who were undergoing GH treatment from childhood to adolescence. METHODS: Sixty-seven pediatric patients with PWS who had GH treatment initiated during childhood between January 2003 and June 2020 were evaluated. To avoid underestimation, we used total body BMD, which was evaluated using dual-X-ray absorptiometry adjusted for the BMD z-score using patient height, sex, and age. RESULTS: In both sexes, age was negatively correlated with the BMD-standard deviation score (SDS) (male: r=-0.156 [p=0.042]; female: r=-0.197 [p=0.043]), which started to decrease in childhood. CONCLUSIONS: The BMD-SDS of patients with PWS decreases gradually despite GH treatment. As there are no clear recommendations about monitoring of bone health in patients with PWS, further studies are needed to improve the guidelines for screening of BMD and treatment of patients with PWS.
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Estatura , Densidade Óssea , Hormônio do Crescimento Humano/administração & dosagem , Síndrome de Prader-Willi/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Síndrome de Prader-Willi/patologia , Prognóstico , Estudos RetrospectivosRESUMO
The prevalence of Gaucher disease (GD) in Japan is much lower than that in Western countries; therefore, data on Japanese pediatric patients with GD type 1 are currently limited. The present study reports on the case of a Japanese pediatric patient with GD type 1 who was diagnosed when she presented with hepatosplenomegaly, thrombocytopenia and slight anemia at the age of 2 years. Serology tests revealed high levels of acid phosphatase (ACP) and angiotensin-converting enzyme (ACE). A bone marrow biopsy revealed the presence of Gaucher cells. Abdominal MRI indicated huge hepatosplenomegaly. Erlenmeyer flask deformity was observed on X-ray examination. MRI of the femora featured a high-intensity area within the diaphysis region. The enzymatic activity of leukocyte ß-glucosidase, the measurement of which is necessary for a definitive diagnosis of GD, had decreased to 186.7 nmol/h/mg (reference range, 1,424.0-2,338.0 nmol/h/mg). Based on these results, the patient was clinically diagnosed with GD. Glucocerebrosidase gene analysis identified the compound heterozygote mutation of F213I (c.754T>A) on exon 7 and L444P (c.1448T>C) on exon 11. Enzyme replacement therapy (ERT) along with an intravenous infusion of 60 U/kg of imiglucerase every other week was initiated following diagnosis. Hemoglobin levels and the platelet count gradually improved and normalized after two years. ACP and ACE levels, biomarkers of the progression of GD, also improved. Abdominal MRI at six months after the initiation of ERT revealed a decrease in the size of the liver and spleen, which normalized after 1 year. Conversely, MRI of the femora indicated no improvement in the high-intensity area within the diaphysis region for 10 years.
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Objective Patients with Prader-Willi syndrome (PWS) are known to have a high mortality rate. However, little is known about the exact reason for this, particularly in adults, because so few reports have been published. The present study examined cardiovascular abnormalities to determine the cause of death in adults with PWS. Methods From September 2017 to April 2019, a total of 18 adults with PWS, and, no history of cardiovascular diseases, were enrolled. We investigated the levels of the cardiovascular biomarkers: high-sensitivity C-reactive protein (hs-CRP) and troponin T (TnT). To estimate the cardiac function, we measured the left ventricular ejection fraction (LVEF), global longitudinal systolic strain (GLS) of the left ventricle, ratio of peak early mitral filling velocity (E) to early diastolic mitral annular velocity (E/e' ratio), mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) using standard and tissue Doppler echocardiography. Results The mean patient age was 28±9 years old. There were 11 men, and the mean body mass index was 45.1 kg/m2. Dyslipidemia (82%), diabetes mellitus (82%) and hypertension (83%) were commonly found as comorbidities. Most patients had elevated levels of hs-CRP (mean 1.007±0.538 mg/dL). The LVEF (mean 61%±5%) showed normal values, while the GLS (mean 15.0%±3.0%) was decreased. The TAPSE was mildly reduced (mean 16±3 mm). Conclusion These results suggest that subtle cardiovascular abnormalities have already begun in young adults with PWS. We need to manage obesity and the resultant obesity-related disorders in order to prevent heart failure and coronary atherosclerosis in PWS patients.
Assuntos
Anormalidades Cardiovasculares , Síndrome de Prader-Willi , Adulto , Ecocardiografia Doppler , Humanos , Masculino , Síndrome de Prader-Willi/complicações , Volume Sistólico , Função Ventricular Esquerda , Adulto JovemRESUMO
OBJECTIVE: To identify risk factors for bleeding in atrial fibrillation (AF) patients treated with anti-coagulants such as warfarin, apixaban, edoxaban, dabigatran, rivaroxaban using a large claims database. METHODS: A claims database for 8926 AF patients from 2004 to 2016 was obtained from JMDC. Inc. We performed a retrospective cohort study in 2796 Japanese AF patients with 4-month screening and 12-month observation periods. Polypharmacy was defined as prescription of over six drugs. Logistic regression analysis was conducted after stratification based on the presence and absence of cerebrovascular diseases to detect the predictive factors for bleeding. RESULTS: Polypharmacy was observed in 815 of 2796 (29.1%) patients. A total of 371 AF patients (13.3%) experienced bleeding in the 12-month observation period. Bleeding risk assessment using multiple logistic regression analysis revealed that the odds ratio for the number of co-administered drugs in the elderly (age for ≥60, ≤74) was not significant in those without and with cerebrovascular diseases (1.05 [0.99-1.12], N.S. and 1.10 [0.96-1.27], N.S.). In contrast, in the young (age for <60), the number of co-administered drugs was a significant predictive factor in those without and with cerebrovascular diseases (1.09 [1.03-1.16], p = 0.0054 and 1.20 [1.05-1.36], p = 0.0059). Other observed predictors were"history of bleeding" in young and elderly, but "polypharmacy" and "start from warfarin" were observed in only young. CONCLUSION: We determined the bleeding risk in the clinical setting using a large claims database. Physicians and pharmacists need to monitor patients for the initial bleeding signs, particularly in those with these predictive risk factors.