Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

Characteristics of Early Paget's Disease in SQSTM1 Mutation Carriers: Baseline Analysis of the ZiPP Study Cohort.

Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Zoledronate in the prevention of Paget's (ZiPP): protocol for a randomised trial of genetic testing and targeted zoledronic acid therapy to prevent SQSTM1-mediated Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 (SQSTM1) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations. METHODS AND ANALYSIS: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events. ETHICS AND DISSEMINATION: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

Smoking cessation support: Indian nursing students' practices, attitudes and perceived barriers.

BACKGROUND: Tobacco use is a significant global health issue. Studies that examined nursing students' attitudes towards smoking cessation support were limited from India. AIM: To assess undergraduate nursing students' practices, beliefs, attitudes and perceived barriers towards smoking cessation support. METHODS: A cross-sectional descriptive design was adopted among undergraduate nursing students (n=178) using self-reported questionnaires. RESULTS: Findings revealed that a majority (68.5%) of the students inquire about their clients' smoking habits and 78.1% of them advise patients who are smokers about the health effects of smoking. Although student nurses hold positive attitudes in the enthusiasm domain (28.8 ± 7.29), the majority of them lack self-efficacy towards smoking cessation support (14.2 ± 4.70). 'Patient's lack of motivation' (89.3%), 'lack of training/knowledge' (88.2%) and 'lack of communication skills' (77.5%) were the major barriers encountered by the participants during tobacco counselling. CONCLUSION: The findings suggest that there is an urgent need to include a tobacco-control curriculum at undergraduate level to improve their competency in giving smoking cessation support.

Knowledge and attitudes of undergraduate nursing students toward dementia: An Indian perspective / Conocimientos y actitudes de los estudiantes de enfermería hacia la demencia: Una perspectiva hindú / Conhecimentos e atitudes dos estudantes de enfermagem para a demência: Uma perspectiva indiana

Objective.This work evaluated nursing students' knowledge and attitudes toward individuals with Alzheimer's disease and dementia. Methodology. This was a transversal, descriptive study carried out with a randomly selected group of nursing students (N = 122) from Bangalore, India, in 2013. The study used the Alzheimer's Disease Knowledge scale (30 questions with true-false options) and the Attitude toward Alzheimer's Disease and Related Dementias scale (20 questions scored with seven Likert-type options; the higher the score, the better the attitude). Results. The findings revealed that 56% of the questions were answered correctly and the average attitude score was 95 ± 1.5. A negative correlation was observed between age and knowledge of dementia (r = -0.323; p < 0.001). Conclusion. The participants have inadequate knowledge of dementia. However, they have positive attitudes towards patients with dementia, giving way to improving their knowledge related to this disease. Thereby, there is urgent need to enhance the undergraduate study plan with respect to the content of this theme and strengthen the attitudes of comprehensive care to individuals with dementia.

Evaluar en los estudiantes de enfermería el conocimiento y las actitudes hacia las personas con enfermedad de Alzheimer y demencia. Metodología. Estudio de descriptivo de tipo transversal llevado a cabo en un grupo seleccionado en forma aleatoria de estudiantes de enfermería (N=122) de Bangalore, India, en 2013. Se utilizaron las escalas: Alzheimer's Disease Knowledge Scale (30 preguntas con opciones verdadero/falso) y The Attitude toward Alzheimer's disease and Related Dementias Scale (20 preguntas calificadas con 7 opciones tipo Likert, a mayor puntaje mejor es la actitud). Resultados. Los hallazgos revelaron que el 56% de las preguntas fueron contestadas correctamente y el promedio puntaje de actitud fue 95±1.5 Se Observó una correlación negativa entre la edad y el conocimiento sobre la demencia (r=-0.323; p<0.001). Conclusion. Los participantes tienen un inadecuado conocimiento sobre la demencia. Sin embargo, que poseen actitudes alentadoras hacia los pacientes con demencia dando espacio a mejorar sus conocimientos relacionados con esta enfermedad. Por lo tanto, hay una necesidad urgente de fortalecer el plan de estudios de pregrado con respecto al contenido de este tema y fortalecer las actitudes el cuidado integral a las personas con demencia.

Objetivo.Avaliar nos estudantes de enfermagem o conhecimento e as atitudes para as pessoas com doença de Alzheimer e demência. Metodologia. Estudo de descritivo de tipo transversal levado a cabo num grupo selecionado em forma aleatória de estudantes de enfermagem (N=122) de Bangalore, índia, em 2013. Utilizaram-se as escalas: Alzheimer's Disease Knowledge Scale (30 perguntas com opções verdadeiro/falso) e The Attitude toward Alzheimer's disease and Related Dementias Scale (20 perguntas qualificadas com 7 opções tipo Likert, a maior pontuação, melhor é a atitude). Resultados. Os resultados revelaram que 56% das perguntas foram contestadas corretamente e a pontuação média de atitude foi 95±1.5 Se Observou uma correlação negativa entre a idade e o conhecimento sobre a demência (r=-0.323; p<0.001). Conclusão. Os participantes têm um inadequado conhecimento sobre a demência. No entanto, que possuem atitudes alentadoras para os pacientes com demência dando espaço a melhorar seus conhecimentos relacionados com esta doença. Portanto, há uma necessidade urgente de fortalecer o plano de estudos de graduação com respeito ao conteúdo deste tema e fortalecer as atitudes o cuidado integral às pessoas com demência.

Bachelor of nursing student' attitude towards people with mental illness and career choices in psychiatric nursing. An Indian perspective.

OBJECTIVE: To examine undergraduate nursing student' attitudes toward people with mental illness and mental health nursing. METHODOLOGY: This was a cross sectional descriptive study carried out among conveniently selected nursing students (N=116). Data was collected through self- reported questionnaires. RESULTS: Majority of the participants agreed that the theoretical (81.1%) and clinical placement (85.4%) was adequate. Similarly, 62.9% would like to apply for a post-basic program in Psychiatric nursing and 69.8% of the students intend to pursue their career as mental health nurses. However, a majority expressed that people with mental illness are unpredictable (80.2%), cannot handle too much responsibility(71.5%), more likely to commit offences or crimes (84.5%) and more likely to be violent (44%). Negative stereotype domain had significant relationships with future career (r=-0.2, p= 0.003), course effectiveness (r=-0.4, p<0.001), valuable contribution (r=-0.3, p<0.001) and readiness of the students (r=-.3, p<.000) domains. CONCLUSION: There is an urgent need to address these negative perceptions among nursing students towards people with mental illness. Innovative teaching strategies and appropriate changes in the nursing curriculum is required to prepare future nurses to deal mental health problems effectively.

Bachelor of nursing student' attitude towards people with mental illness and career choices in psychiatric nursing. An Indian perspective / Actitudes de las estudiantes de Enfermería hacia las personas con enfermedad mental y futuro desempeño profesional en enfermería psiquiátrica. Una perspectiva hindú / Atitudes das estudantes de Enfermagem para as pessoas com doença mental e futuro desempenho profissional em enfermagem psiquiátrica. Uma perspectiva indiana

Objective. To examine undergraduate nursing student' attitudes toward people with mental illness and mental health nursing. Methodology. This was a cross sectional descriptive study carried out among conveniently selected nursing students (N=116). Data was collected through self- reported questionnaires. Results: Majority of the participants agreed that the theoretical (81.1%) and cpnical placement (85.4%) was adequate. Similarly, 62.9% would pke to apply for a post-basic program in Psychiatric nursing and 69.8% of the students intend to pursue their career as mental health nurses. However, a majority expressed that people with mental illness are unpredictable (80.2%), cannot handle too much responsibipty (71.5%), more pkely to commit offences or crimes (84.5%) and more pkely to be violent (44%). Negative stereotype domain had significant relationships with future career (r=-0.2, p= 0.003), course effectiveness (r=-0.4, p<0.001), valuable contribution (r=-0.3, p<0.001) and readiness of the students (r=-.3, p<.000) domains. Conclusion. There is an urgent need to address these negative perceptions among nursing students towards people with mental illness. Innovative teaching strategies and appropriate changes in the nursing curriculum is required to prepare future nurses to deal mental health problems effectively.

Objetivo. Explorar en las estudiantes de enfermería las actitudes hacia las personas con enfermedad mental y su relación con la elección de desempeño profesional en enfermería psiquiátrica. Metodología. Estudio descriptivo de corte transversal reapzado en 2014 una muestra por conveniencia de 116 estudiantes de tercero y cuarto año de enfermería. Se utipzó la Encuesta sobre Educación en Salud Mental en Enfermería de Hapell et al., la cual fue respondida por autorreporte. Resultados. El 98.3% de los participantes fueron mujeres. La mayoría de los encuestados estuvieron de acuerdo en que la teoría (81.1%) y la práctica clínica (85.4%) fueron adecuados. Del mismo modo, a un 62.9% le gustaría appcar a un programa avanzado de enfermería psiquiátrica y 69.8% de los estudiantes tienen la intención de continuar su carrera como enfermeras de salud mental. Sin embargo, la mayoría expresó que las personas con enfermedad mental son impredecibles (80.2%), no pueden manejar demasiada responsabipdad (71.5%) y que son más propensos a cometer deptos o crímenes (84.5%) y ser violentos (44.0%). El estereotipo negativo se asoció significativamente con los dominios de elección de la futura carrera (r = -.2), efectividad del curso (r = -. 4), la contribución del curso (r = -. 3) y la preparación de los estudiantes (r = -. 3). Conclusión. Los estudiantes de enfermería tienen percepciones negativas hacia las personas con enfermedad mental. Es necesario que las instituciones que forman a los futuros profesionales introduzcan los cambios que sean necesarios en el plan de estudios con el fin de prepararlos para tratar problemas de salud mental de manera efectiva.

Objetivo. Explorar nas estudantes de enfermagem as atitudes para as pessoas com doença mental e sua relação com a eleição de desempenho profissional em enfermagem psiquiátrica. Metodologia. Estudo descritivo de corte transversal reapzado em 2014 uma mostra por conveniência de 116 estudantes de terceiro e quarto ano de enfermagem. Utipzou-se a Enquete sobre Educação em Saúde Mental em Enfermagem de Hapell et al., a qual foi respondida por autorreporte. Resultados. 98.3% dos participantes foram mulheres. A maioria dos interrogados estiveram de acordo em que a teoria (81.1%) e a prática clínica (85.4%) foram adequados. Do mesmo modo, a um 62.9% lhe agradaria appcar a um programa avançado de enfermagem psiquiátrica e 69.8% dos estudantes têm a intenção de continuar sua carreira como enfermeiras de saúde mental. No entanto, a maioria expressou que as pessoas com doença mental são imprevisíveis (80.2%), não podem manejar demasiada responsabipdade (71.5%) e que são mais propensos a cometer deptos ou crimes (84.5%) e ser violentos (44.0%). O estereótipo negativo se associou significativamente com os domínios de eleição da futura carreira (r = -0.2), efetividade do curso (r = -0.4), a contribuição do curso (r = -0.3) e a preparação dos estudantes (r = -0.3). Conclusão. Os estudantes de enfermagem têm percepções negativas para as pessoas com doença mental. É necessário que as instituições que formam aos futuros profissionais introduzam as mudanças que sejam necessários no plano de estudos com o fim de prepará-los para tratar problemas de saúde mental de maneira efetiva.

Knowledge and attitudes of undergraduate nursing students toward dementia: An Indian perspective.

OBJECTIVE: This work evaluated nursing students' knowledge and attitudes toward individuals with Alzheimer's disease and dementia. METHODOLOGY: This was a transversal, descriptive study carried out with a randomly selected group of nursing students (N = 122) from Bangalore, India, in 2013. The study used the Alzheimer's Disease Knowledge scale (30 questions with true-false options) and the Attitude toward Alzheimer's Disease and Related Dementias scale (20 questions scored with seven Likert-type options; the higher the score, the better the attitude). RESULTS: The findings revealed that 56% of the questions were answered correctly and the average attitude score was 95 ± 1.5. A negative correlation was observed between age and knowledge of dementia (r = -0.323; p < 0.001). CONCLUSION: The participants have inadequate knowledge of dementia. However, they have positive attitudes towards patients with dementia, giving way to improving their knowledge related to this disease. Thereby, there is urgent need to enhance the undergraduate study plan with respect to the content of this theme and strengthen the attitudes of comprehensive care to individuals with dementia.

Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation.

Inter-individual response differences to vitamin D and Ca supplementation may be under genetic control through vitamin D and oestrogen receptor genes, which may influence their absorption and/or metabolism. Metabolomic studies on blood and urine from subjects supplemented with Ca and vitamin D reveal different metabolic profiles that segregate with genotype. Genotyping was performed for oestrogen receptor 1 gene (ESR1) and vitamin D receptor gene (VDR) in fifty-six postmenopausal women. Thirty-six women were classified as low bone density as determined by a heel ultrasound scan and twenty women had normal bone density acting as 'controls'. Those with low bone density (LBD) were supplemented with oral Ca and vitamin D and were classified according to whether they were 'responders' or 'non-responders' according to biochemical results before and after therapy compared to controls receiving no supplementation. Metabolomic studies on serum and urine were done for the three groups at 0 and 3 months of therapy using NMR spectroscopy with pattern recognition. The 'non-responder' group showed a higher frequency of polymorphisms in the ESR1 (codons 10 and 325) and VDR (Bsm1 and Taq1), compared with to the 'responders'. The wild-type genotype for Fok1 was more frequent in those with LBD (70 %) compared with the control group (10 %). Distinctive patterns of metabolites were displayed by NMR studies at baseline and 3 months of post-treatment, segregating responders from non-responders and controls. Identification of potential 'non-responders' to vitamin D and Ca, before therapy, based on a genomic and/or metabolomic profile would allow targeted selection of optimal therapy on an individual basis.

Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors.

BACKGROUND: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors. MATERIALS AND METHODS: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received. RESULTS: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP. CONCLUSION: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Anaphylactic reaction to intravenous sinistrin (Inutest).

Inulin clearance is the 'gold standard' for the determination of glomerular filtration rate. This is the first report of anaphylaxis following intravenous administration of inulin.