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1.
Int J Mol Sci ; 25(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39000600

RESUMO

Women with type 2 diabetes (T2D) have a higher risk of being diagnosed with breast cancer and have worse survival than non-diabetic women if they do develop breast cancer. However, more research is needed to elucidate the biological underpinnings of these relationships. Here, we found that forkhead box A1 (FOXA1), a forkhead family transcription factor, and metformin (1,1-dimethylbiguanide hydrochloride), a medication used to treat T2D, may impact hormone-receptor-positive (HR+) breast cancer (BC) tumor cell growth and metastasis. Indeed, fourteen diabetes-associated genes are highly expressed in only three HR+ breast cancer cell lines but not the other subtypes utilizing a 53,805 gene database obtained from NCBI GEO. Among the diabetes-related genes, FOXA1, MTA3, PAK4, FGFR3, and KIF22 were highly expressed in HR+ breast cancer from 4032 breast cancer patient tissue samples using the Breast Cancer Gene Expression Omnibus. Notably, elevated FOXA1 expression correlated with poorer overall survival in patients with estrogen-receptor-positive/progesterone-receptor-positive (ER+/PR+) breast cancer. Furthermore, experiments demonstrated that loss of the FOXA1 gene inhibited tumor proliferation and invasion in vitro using MCF-7 and T47D HR+ breast cancer cell lines. Metformin, an anti-diabetic medication, significantly suppressed tumor cell growth in MCF-7 cells. Additionally, either metformin treatment or FOXA1 gene deletion enhanced tamoxifen-induced tumor growth inhibition in HR+ breast cancer cell lines within an ex vivo three-dimensional (3D) organoid model. Therefore, the diabetes-related medicine metformin and FOXA1 gene inhibition might be a new treatment for patients with HR+ breast cancer when combined with tamoxifen, an endocrine therapy.


Assuntos
Neoplasias da Mama , Proliferação de Células , Fator 3-alfa Nuclear de Hepatócito , Metformina , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Metformina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Invasividade Neoplásica , Células MCF-7 , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética
2.
Materials (Basel) ; 17(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38793509

RESUMO

This work is focused on a novel, promising low temperature phase change material (PCM), based on the eutectic Glauber's salt composition. To allow phase transition within the refrigeration range of temperatures of +5 °C to +12 °C, combined with a high repeatability of melting-freezing processes, and minimized subcooling, the application of three variants of sodium carboxymethyl cellulose (Na-CMC) with distinct molecular weights (700,000, 250,000, and 90,000) is considered. The primary objective is to optimize the stabilization of this eutectic PCM formulation, while maintaining the desired enthalpy level. Preparation methods are refined to ensure repeatability in mixing components, thereby optimizing performance and stability. Additionally, the influence of Na-CMC molecular weight on stabilization is examined through differential scanning calorimetry (DSC), T-history, and rheology tests. The PCM formulation of interest builds upon prior research in which borax, ammonium chloride, and potassium chloride were used as additives to sodium sulfate decahydrate (Glauber's salt), prioritizing environmentally responsible materials. The results reveal that CMC with molecular weights of 250 kg/mol and 90 kg/mol effectively stabilize the PCM without phase separation issues, slowing crystallization kinetics. Conversely, CMC of 700 kg/mol proved ineffective due to the disruption of gel formation at its low gel point, hindering higher concentrations. Calculations of ionic concentration indicate higher Na ion content in PCM stabilized with 90 kg/mol CMC, suggesting increased ionic interactions and gel strength. A tradeoff is discovered between the faster crystallization in lower molecular weight CMC and the higher concentration required, which increases the amount of inert material that does not participate in the phase transition. After thermal cycling, the best formulation had a latent heat of 130 J/g with no supercooling, demonstrating excellent performance. This work advances PCM's reliability as a thermal energy storage solution for diverse applications and highlights the complex relationship between Na-CMC molecular weight and PCM stabilization.

3.
Cureus ; 15(11): e48583, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38090398

RESUMO

Nosocomial infections form one of the most challenging tasks to deal with in a hospital setting. The burden of hospital-acquired infections (HAI) significantly affects the patient's cost of medical treatment and seriously impacts the economy of a developing country like India. Haphazard antibiotic use for the treatment of these infections has led to the development of resistance among the microbes, and factors that complicate microbial eradication further worsen the scenario. A large percentage of the HAI are preventable by simply following up various protocols which when supported by judicious antibiotic use can declutter the severity of the problem. Organized infection control measures, trained hospital staff, and continuous surveillance of HAI in healthcare settings will help deal with nosocomial infections. Although the ability to deal with HAI in a patient might determine his survival after acquiring a nosocomial infection, prevention remains the best option at all times. Lowering down the burden of nosocomial infections is of utmost importance since it contributes significantly to the overall resource utilization of the hospital and the country. Implementing the use of nanoparticles and nanotechnology in delivering target-specific drugs might be helpful in preventing antibiotic resistance. Taking into account reports of nosocomial infection patterns in various centres of India, the seriousness and consequences of HAI are uncovered in this article.

4.
Pancreatology ; 23(5): 522-529, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37296006

RESUMO

OBJECTIVES: To develop a bounding-box-based 3D convolutional neural network (CNN) for user-guided volumetric pancreas ductal adenocarcinoma (PDA) segmentation. METHODS: Reference segmentations were obtained on CTs (2006-2020) of treatment-naïve PDA. Images were algorithmically cropped using a tumor-centered bounding box for training a 3D nnUNet-based-CNN. Three radiologists independently segmented tumors on test subset, which were combined with reference segmentations using STAPLE to derive composite segmentations. Generalizability was evaluated on Cancer Imaging Archive (TCIA) (n = 41) and Medical Segmentation Decathlon (MSD) (n = 152) datasets. RESULTS: Total 1151 patients [667 males; age:65.3 ± 10.2 years; T1:34, T2:477, T3:237, T4:403; mean (range) tumor diameter:4.34 (1.1-12.6)-cm] were randomly divided between training/validation (n = 921) and test subsets (n = 230; 75% from other institutions). Model had a high DSC (mean ± SD) against reference segmentations (0.84 ± 0.06), which was comparable to its DSC against composite segmentations (0.84 ± 0.11, p = 0.52). Model-predicted versus reference tumor volumes were comparable (mean ± SD) (29.1 ± 42.2-cc versus 27.1 ± 32.9-cc, p = 0.69, CCC = 0.93). Inter-reader variability was high (mean DSC 0.69 ± 0.16), especially for smaller and isodense tumors. Conversely, model's high performance was comparable between tumor stages, volumes and densities (p > 0.05). Model was resilient to different tumor locations, status of pancreatic/biliary ducts, pancreatic atrophy, CT vendors and slice thicknesses, as well as to the epicenter and dimensions of the bounding-box (p > 0.05). Performance was generalizable on MSD (DSC:0.82 ± 0.06) and TCIA datasets (DSC:0.84 ± 0.08). CONCLUSION: A computationally efficient bounding box-based AI model developed on a large and diverse dataset shows high accuracy, generalizability, and robustness to clinically encountered variations for user-guided volumetric PDA segmentation including for small and isodense tumors. CLINICAL RELEVANCE: AI-driven bounding box-based user-guided PDA segmentation offers a discovery tool for image-based multi-omics models for applications such as risk-stratification, treatment response assessment, and prognostication, which are urgently needed to customize treatment strategies to the unique biological profile of each patient's tumor.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Processamento de Imagem Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Redes Neurais de Computação , Neoplasias Pancreáticas/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico por imagem , Ductos Pancreáticos
5.
Cureus ; 14(10): e29848, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36348910

RESUMO

ST-segment elevation myocardial infarction (STEMI) is a known medical exigency that has seen considerable advances in medical treatment, dramatically boosting survival rates. Post myocardial infarction ventricular rupture is a major serious mechanical complication following myocardial infarction. We present a case of a 68-year-old male admitted to the emergency department with heaviness in the chest, for which electrocardiography was done and it was suggestive of anterior and lateral wall myocardial infarction. After six hours he experienced breathlessness, jugular venous pressure (JVP) was raised, and auscultation revealed early systolic murmur at apex suggestive of ventricular septal rupture. An urgent echocardiogram was done and it confirmed the diagnosis of ventricular septal rupture (VSR). To enhance the prognosis, early identification and appropriate care are required, which necessitate a thorough clinical evaluation that raises the possibility of mechanical problem, as late presentation is one of the major risk factors for developing VSR. VSR can manifest itself in numerous ways, based on the patient's condition. Right clinical judgement and ECG are required to establish a quick diagnosis, as a result, to determine the most appropriate treatment at the appropriate time.

6.
Cureus ; 14(9): e29160, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36258928

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic made us reframe a lot of the strategies followed in medical practice and ophthalmological services and procedures were also not spared, including corneal transplantation or keratoplasty, the most routine procedure performed worldwide. The prevalence of viral presence in the ocular tissue necessitates a focus on the handling of donor ocular tissue and the functioning of eye banks, ensuring it doesn't risk the patient and the doctor's safety. Restrictions in the movement of people during the pandemic limited the number of donations, causing a shortage of tissues, with a large number of people already waitlisted for tissue needs. The lesson from the COVID-19 pandemic directs us to look for long-term corneal storage techniques taking into consideration the tissue viability time and the possibility of post-pandemic shortages. Although there is not a significant number of reports, the cases of corneal graft rejection post-vaccination against COVID-19 are highlighted and thus should form a part of the lookout while evaluating the possible cause of rejection of grafts. This article summarises the overall impact of the pandemic on corneal transplantation and the possible future of storage techniques, which need to evolve and be adapted.

7.
RSC Adv ; 12(32): 20599-20602, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35919152

RESUMO

The separation of butanes and butenes using MOF-74 (with two reticular MOFs with different pore sizes, Ni-IRMOF-74-I and Ni-IRMOF-74-II) was evaluated computationally using density functional theory. We identified that C4 alkene versus alkane selectivity stems from π-d chemical interactions, whereas selectivity differences among butenes stem from steric implications.

8.
Heart Lung Circ ; 31(2): 177-182, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34217582

RESUMO

OBJECTIVE: Chest pain is a large health care burden in Australia and around the world. Its management requires specialist assessment and diagnostic tests, which can be costly and often lead to unnecessary hospital admissions. There is a growing unmet clinical need to improve the efficiency and management of chest pain. This study aims to show the cost-benefit of rapid access chest pain clinics (RACC) as an alternative to hospital admission. DESIGN: Retrospective cost-benefit analysis for 12 months. SETTING: RACCs in three Sydney tertiary referral hospitals. MAIN OUTCOME MEASURES: Cost per patient. RESULTS: Hospitals A, B and C implemented RACCs but each operating with slightly different staffing, referral patterns, and diagnostic services. All RACCs had similar costs per patient of AUD$455.25, AUD$427.12 and AUD$474.45, hospitals A, B and C respectively, and similar cost benefits per patient of AUD$1,168.75, AUD$1,196.88 and AUD$1,149.55, respectively. At least 28%, 26% and 29% of these RACC patients for hospitals A, B, and C, respectively, would have otherwise had to have been admitted to hospital for the model to be cost-beneficial. CONCLUSION: This study shows that a RACC model of care is cost-beneficial in the state of NSW as an alternative strategy to inpatient care for managing chest pain. Scaling up to a national level could represent an even larger benefit for the Australian health system.


Assuntos
Dor no Peito , Clínicas de Dor , Austrália/epidemiologia , Dor no Peito/diagnóstico , Dor no Peito/epidemiologia , Dor no Peito/terapia , Análise Custo-Benefício , Humanos , Estudos Retrospectivos
10.
JACC Cardiovasc Interv ; 12(5): 459-469, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30846085

RESUMO

OBJECTIVES: The authors sought to prospectively determine the safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) Clinical Pathway. BACKGROUND: Transfemoral transcatheter aortic valve replacement (TAVR) is an alternative to surgery in high- and intermediate-risk patients; however, hospital stays average at least 6 days in most trials. The Vancouver 3M Clinical Pathway is focused on next-day discharge, made possible by the use of objective screening criteria as well as streamlined peri- and post-procedural management guidelines. METHODS: Patients were enrolled from 6 low-volume (<100 TAVR/year), 4 medium-volume, and 3 high-volume (>200 TAVR/year) centers in Canada and the United States. The primary outcomes were a composite of all-cause death or stroke by 30 days and the proportion of patients successfully discharged home the day following TAVR. RESULTS: Of 1,400 screened patients, 411 were enrolled at 13 centers and received a SAPIEN XT (58.2%) or SAPIEN 3 (41.8%) valve (Edwards Lifesciences, Irvine, California). In centers enrolling exclusively in the study, 55% of screened patients were enrolled. The median age was 84 years (interquartile range: 78 to 87 years) with a median STS score of 4.9% (interquartile range: 3.3% to 6.8%). Next-day discharge home was achieved in 80.1% of patients, and within 48 h in 89.5%. The composite of all-cause mortality or stroke by 30 days occurred in 2.9% (95% confidence interval: 1.7% to 5.1%), with neither component of the primary outcome affected by hospital TAVR volume (p = 0.51). Secondary outcomes at 30 days included major vascular complication 2.4% (n = 10), readmission 9.2% (n = 36), cardiac readmission 5.7% (n = 22), new permanent pacemaker 5.7% (n = 23), and >mild paravalvular regurgitation 3.8% (n = 15). CONCLUSIONS: Adherence to the Vancouver 3M Clinical Pathway at low-, medium-, and high-volume TAVR centers allows next-day discharge home with excellent safety and efficacy outcomes.


Assuntos
Valva Aórtica/cirurgia , Cateterismo Periférico , Procedimentos Clínicos , Artéria Femoral , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Tempo de Internação , Alta do Paciente , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Canadá , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/mortalidade , Feminino , Próteses Valvulares Cardíacas , Humanos , Masculino , Readmissão do Paciente , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Estudos Prospectivos , Desenho de Prótese , Punções , Medição de Risco , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/instrumentação , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do Tratamento , Estados Unidos
11.
Can J Cardiol ; 34(7): 905-913, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29887218

RESUMO

Cardiovascular disease (CVD) is a leading global cause of death and morbidity and prevention needs to be strengthened to tackle this. Mobile health (mHealth) might present a novel and effective solution in CVD prevention, and interest in mHealth has grown dramatically since the advent of the smartphone. In this review, we discuss mHealth interventions that target multiple cardiovascular risk factors simultaneously in the context of primary as well as secondary prevention. There is some evidence that mHealth interventions improve a range of individual CVD risk factors, but a relative paucity of evidence on mHealth interventions improving multiple CVD risk factors simultaneously. The existing data suggest mHealth programs improve overall CVD risk, at least in the short term. Interpretation of the evidence is difficult in the context of poor methodology and mHealth modalities often being a part of large complex interventions. In this review we identify a number of unanswered questions including: which mode of mHealth (or combination of interventions) would be most effective, what is the durability of intervention effects, and what degree of personalization and interactivity is required.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Atenção à Saúde/métodos , Prevenção Secundária/métodos , Telemedicina/organização & administração , Humanos
12.
Aust J Prim Health ; 24(3): 256-262, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29789100

RESUMO

The 'Tobacco, Exercise and Diet Messages' (TEXT ME) study was a 6-month, single-centre randomised clinical trial (RCT) that found a text message support program improved levels of cardiovascular risk factors in patients with coronary heart disease (CHD). The current analyses examined whether receipt of text messages influenced participants' engagement with conventional healthcare resources. The TEXT ME study database (N=710) was linked with routinely collected health department databases. Number of doctor consultations, investigations and cardiac medication prescriptions in the two study groups were compared. The most frequently accessed health service was consultations with a General Practitioner (mean 7.1, s.d. 5.4). The numbers of medical consultations, biochemical tests or cardiac-specific investigations were similar between the study groups. There was at least one prescription registered for statin, ACEI/ARBs and ß-blockers in 79, 66 and 50% of patients respectively, with similar refill rates in both the study groups. The study identified TEXT ME text messaging program did not increase use of Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) captured healthcare services. The observed benefits of TEXT ME reflect direct effects of intervention independent of conventional healthcare resource engagement.


Assuntos
Doença das Coronárias/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Envio de Mensagens de Texto , Exercício Físico , Humanos , Estilo de Vida
13.
Interv Cardiol Clin ; 7(2): 243-252, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29526292

RESUMO

Major procedural complications related to left atrial appendage occlusion (LAAO) are relatively infrequent but may be associated with major morbidity and mortality. LAAO operators should be knowledgeable about these potential complications. Prompt recognition and treatment are necessary to avoid rapid deterioration and dire consequences. With stringent guidelines on operator training, competency requirements, and procedural-technical refinements, LAAO can be performed safely with low complication rates. This article focuses on commonly used devices, as well as prevention, treatment, and management of complications of LAOO.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Cateterismo Cardíaco/efeitos adversos , Dispositivo para Oclusão Septal/efeitos adversos , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Cateterismo Cardíaco/métodos , Tamponamento Cardíaco/epidemiologia , Tamponamento Cardíaco/mortalidade , Tamponamento Cardíaco/prevenção & controle , Tamponamento Cardíaco/terapia , Comorbidade , Humanos , Incidência , Derrame Pericárdico/epidemiologia , Derrame Pericárdico/mortalidade , Derrame Pericárdico/prevenção & controle , Derrame Pericárdico/terapia , Período Perioperatório , Guias de Prática Clínica como Assunto , Preceptoria/normas , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/terapia , Trombose/epidemiologia , Trombose/mortalidade , Trombose/prevenção & controle , Trombose/terapia , Resultado do Tratamento
14.
BMJ Open ; 8(1): e019463, 2018 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-29374674

RESUMO

BACKGROUND: Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. OBJECTIVE: The TEXTMEDS (TEXT messages to improve MEDication adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). STUDY DESIGN: A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low-density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and process evaluations to assess acceptability, utility and cost-effectiveness. SUMMARY: The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. ETHICS AND DISSEMINATION: Primary ethics approval was received from Western Sydney Local Health District Human Research Ethics Committee (HREC2012/12/4.1 (3648) AU RED HREC/13/WMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12613000793718; Pre-results.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Promoção da Saúde/métodos , Adesão à Medicação , Educação de Pacientes como Assunto/métodos , Prevenção Secundária/métodos , Telemedicina/métodos , Envio de Mensagens de Texto , Pressão Sanguínea , Telefone Celular , LDL-Colesterol/sangue , Dieta , Exercício Físico , Feminino , Humanos , Estilo de Vida , Masculino , Motivação , Readmissão do Paciente , Sistemas de Alerta , Projetos de Pesquisa , Fatores de Risco , Método Simples-Cego
16.
Hypertension ; 70(1): 85-93, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28584013

RESUMO

There is a critical need for blood pressure-lowering strategies that have greater efficacy and minimal side effects. Low-dose combinations hold promise in this regard, but there are few data on very-low-dose therapy. We, therefore, conducted a systematic review and meta-analysis of randomized controlled trials with at least one quarter-dose and one placebo and standard-dose monotherapy arm. A search was conducted of Medline, Embase, Cochrane Registry, Food and Drug Administration, and European Medicinal Agency websites. Data on blood pressure and adverse events were pooled using a fixed-effect model, and bias was assessed using Cochrane risk of bias. The review included 42 trials involving 20 284 participants. Thirty-six comparisons evaluated quarter-dose with placebo and indicated a blood pressure reduction of -4.7/-2.4 mm Hg (P<0.001). Six comparisons were of dual quarter-dose therapy versus placebo, observing a -6.7/ -4.4 mm Hg (P<0.001) blood pressure reduction. There were no trials of triple quarter-dose combination versus placebo, but one quadruple quarter-dose study observed a blood pressure reduction of -22.4/-13.1 mm Hg versus placebo (P<0.001). Compared with standard-dose monotherapy, the blood pressure differences achieved by single (37 comparisons), dual (7 comparisons), and quadruple (1 trial) quarter-dose combinations were +3.7/+2.6 (P<0.001), +1.3/-0.3 (NS), and -13.1/-7.9 (P<0.001) mm Hg, respectively. In terms of adverse events, single and dual quarter-dose therapy was not significantly different from placebo and had significantly fewer adverse events compared with standard-dose monotherapy. Quarter-dose combinations could provide improvements in efficacy and tolerability of blood pressure-lowering therapy.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacocinética , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Humanos , Conduta do Tratamento Medicamentoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Lancet ; 389(10073): 1035-1042, 2017 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-28190578

RESUMO

BACKGROUND: Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. METHODS: We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. FINDINGS: Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. INTERPRETATION: The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. FUNDING: National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.


Assuntos
Anti-Hipertensivos , Hipertensão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Oral , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Atenolol/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hipertensão/tratamento farmacológico , Irbesartana , Adesão à Medicação , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Resultado do Tratamento
19.
JMIR Mhealth Uhealth ; 4(4): e127, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27847350

RESUMO

BACKGROUND: Mobile health (mHealth) has huge potential to deliver preventative health services. However, there is paucity of literature on theoretical constructs, technical, practical, and regulatory considerations that enable delivery of such services. OBJECTIVES: The objective of this study was to outline the key considerations in the development of a text message-based mHealth program; thus providing broad recommendations and guidance to future researchers designing similar programs. METHODS: We describe the key considerations in designing the intervention with respect to functionality, technical infrastructure, data management, software components, regulatory requirements, and operationalization. We also illustrate some of the potential issues and decision points utilizing our experience of developing text message (short message service, SMS) management systems to support 2 large randomized controlled trials: TEXT messages to improve MEDication adherence & Secondary prevention (TEXTMEDS) and Tobacco, EXercise and dieT MEssages (TEXT ME). RESULTS: The steps identified in the development process were: (1) background research and development of the text message bank based on scientific evidence and disease-specific guidelines, (2) pilot testing with target audience and incorporating feedback, (3) software-hardware customization to enable delivery of complex personalized programs using prespecified algorithms, and (4) legal and regulatory considerations. Additional considerations in developing text message management systems include: balancing the use of customized versus preexisting software systems, the level of automation versus need for human inputs, monitoring, ensuring data security, interface flexibility, and the ability for upscaling. CONCLUSIONS: A merging of expertise in clinical and behavioral sciences, health and research data management systems, software engineering, and mobile phone regulatory requirements is essential to develop a platform to deliver and manage support programs to hundreds of participants simultaneously as in TEXT ME and TEXTMEDS trials. This research provides broad principles that may assist other researchers in developing mHealth programs.

20.
Heart Asia ; 8(2): 32-38, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27752288

RESUMO

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in India. Text message based prevention programs have demonstrated reduction in cardiovascular risk factors among patients with CHD in selected populations. Customisation is important as behaviour change is influenced by culture and linguistic context. OBJECTIVES: To customise a mobile phone text message program supporting behaviour and treatment adherence in CHD for delivery in North India. METHODS: We used an iterative process with mixed methods involving three phases: (1) Initial translation, (2) Review and incorporation of feedback including review by cardiologists in India to assess alignment with local guidelines and by consumers on perceived utility and clarity and (3) Pilot testing of message management software. RESULTS: Messages were translated in three ways: symmetrical translation, asymmetrical translation and substitution. Feedback from cardiologists and 25 patients was incorporated to develop the final bank. Patients reported Hinglish messages were easy to understand (93%) and useful (78%). The software located in Australia successfully delivered messages to participants based in Delhi-surrounds (India). CONCLUSIONS: Our process for customisation of a text message program considered cultural, linguistic and the medical context of potential participants. This is important in optimising intervention fidelity across populations enabling examination of the generalisability of text message programs across populations. We also demonstrated the customised program was acceptable to patients in India and that a centralised cross-country delivery model was feasible. This process could be used as a guide for other groups seeking to customise their programs. TRIAL REGISTRATION NUMBER: TEXTMEDS Australia (Parent study)-ACTRN 12613000793718.

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