Feasibility of Integrating MEditatioN inTO heaRt Disease (the MENTOR Study): A Phase II Randomized Controlled Trial.

BACKGROUND: Comorbid depression and/or anxiety symptoms occur in 25% of patients attending cardiac rehabilitation (CR) programs and are associated with poorer prognosis. There is a need to evaluate psychological interventions, including meditation, that have potential to improve psychological health in CR programs. AIMS: The aim of this study was to determine the feasibility and acceptability of integrating a meditation intervention into an existing Australian CR program for the reduction of depression and anxiety symptoms. METHODS: This was a mixed-methods feasibility randomized controlled trial. Thirty-one patients with CVD and, at a minimum, mild depression and/or anxiety symptoms were randomized to meditation and standard CR or to standard CR alone. A 16-minute guided group meditation was delivered face-to-face once a week for 6 weeks, with daily self-guided meditation practice between sessions. Feasibility outcomes included screening, recruitment, and retention. Semistructured interviews of patients' (n = 10) and health professionals' (n = 18) perspectives of intervention participation and delivery were undertaken to assess acceptability. Between-group differences in depression, anxiety, stress, self-efficacy for mindfulness, and health status at 6 and 12 weeks were also assessed. RESULTS AND CONCLUSION: Meditation was considered feasible, with 83% (12/15) of the intervention group completing an average of 3.13 (SD, 2.56) out of 6 group meditation sessions and 5.28 (SD, 8.50) self-guided sessions. Meditation was considered acceptable by patients, clinicians, and health managers. Between-group differences in the number of CR sessions completed favored the intervention group in per-protocol analyses (intervention group vs control group, 12 vs 9 sessions; P = .014), which suggests that meditation may be useful to improve patients' adherence to exercise-based CR program.

The Role of Lifestyle and Cardiovascular Risk Factors in Dropout From an Australian Cardiac Rehabilitation Program. A Longitudinal Cohort Study.

BACKGROUND: Cardiac rehabilitation (CR) programs reduce the risk of further cardiac events and improve the ability of people living with cardiovascular disease to manage their symptoms. However, many people who experience a cardiac event do not attend or fail to complete their CR program. Little is known about the characteristics of people who drop out compared to those who complete CR. AIMS: To identify subgroups of patients attending a cardiac rehabilitation program who are more likely to dropout prior to final assessment by (1) calculating the dropout rate from the program, (2) quantifying the association between dropout and socio-demographic, lifestyle, and cardiovascular risk factors, and (3) identifying independent predictors of dropout. METHODS: The study population is from a large metropolitan teaching hospital in Sydney, Australia, and consists of all participants consecutively enrolled in an outpatient CR program between 2006 and 2017. Items assessed included diagnoses and co-morbidities, quality of life (SF-36), psychological health (DASS-21), lifestyle factors and physical assessment. Dropout was defined as failure to complete the outpatient CR program and post CR assessment. RESULTS: Of the 3,350 patients enrolled in the CR program, 784 (23.4%; 95%CI: 22.0-24.9%) dropped out prior to completion. The independent predictors of dropout were smoking (OR 2.4; 95%CI: 1.9-3.0), being separated or divorced (OR 2.0; 95%CI: 1.5-2.6), younger age (<55 years) (OR 1.9; 95%CI: 1.6-2.4), obesity (OR 1.6; 95%CI: 1.3-2.0), diabetes (OR 1.6; 95%CI: 1.3-2.0), sedentary lifestyle (OR 1.3; 95%CI: 1.1-1.6) and depressive symptoms (OR 1.3; 95%CI: 1.1-1.6). CONCLUSION: To improve the CR program completion rate, clinicians need to consider the impact of socio-demographic, lifestyle, and cardiovascular risk factors on their patients' ability to complete CR. Tailored strategies which target the independent predictors of dropout are required to promote adherence to CR programs and thereby potentially reduce long-term cardiovascular risk.

A Case of Cribriform-Morular Thyroid Carcinoma Presenting Without Thyroid Nodule.

Cribriform-morular thyroid carcinoma is a rare type of thyroid cancer. It has a strong association with familial adenomatous polyposis (FAP), a hereditary genetic disorder that predisposes individuals to the development of numerous polyps in the colon and rectum. We describe the case of a young female patient who presented with an enlarging goiter, notably without detectable thyroid nodules or masses on ultrasound, who after total thyroidectomy was found to have cribriform-morular thyroid carcinoma. This diagnosis led to genetic testing and diagnosis of FAP syndrome. We demonstrate that this rare thyroid carcinoma may present with nonsuspicious findings on sonographic evaluation while being a valuable harbinger in the diagnosis of FAP syndrome.

Lidocaine for Neuropathic Cancer Pain (LiCPain): study protocol for a mixed-methods pilot study.

INTRODUCTION: Many patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine (lignocaine) has the potential to help manage neuropathic cancer-related pain when administered as an extended, continuous subcutaneous infusion. Data support lidocaine as a promising, safe agent in this setting, warranting further evaluation in robust, randomised controlled trials. This protocol describes the design of a pilot study to evaluate this intervention and explains the pharmacokinetic, efficacy and adverse effects evidence informing the design. METHODS AND ANALYSIS: A mixed-methods pilot study will determine the feasibility of an international first, definitive phase III trial to evaluate the efficacy and safety of an extended continuous subcutaneous infusion of lidocaine for neuropathic cancer-related pain. This study will comprise: a phase II double-blind randomised controlled parallel-group pilot of subcutaneous infusion of lidocaine hydrochloride 10% w/v (3000 mg/30 mL) or placebo (sodium chloride 0.9%) over 72 hours for neuropathic cancer-related pain, a pharmacokinetic substudy and a qualitative substudy of patients' and carers' experiences. The pilot study will provide important safety data and help inform the methodology of a definitive trial, including testing proposed recruitment strategy, randomisation, outcome measures and patients' acceptability of the methodology, as well as providing a signal of whether this area should be further investigated. ETHICS AND DISSEMINATION: Participant safety is paramount and standardised assessments for adverse effects are built into the trial protocol. Findings will be published in a peer-reviewed journal and presented at conferences. This study will be considered suitable to progress to a phase III study if there is a completion rate where the CI includes 80% and excludes 60%. The protocol and Patient Information and Consent Form have been approved by Sydney Local Health District (Concord) Human Research Ethics Committee 2019/ETH07984 and University of Technology Sydney ETH17-1820. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12617000747325.

Health professionals' perspectives of integrating meditation into cardiovascular care: A descriptive qualitative study.

Preliminary research suggests that meditation may provide benefits in psychological health and well-being in people with cardiovascular disease (CVD). However, little is known about health professionals' perceptions of the barriers and facilitators to integrating meditation into CVD. A descriptive qualitative study design with semi-structured interviews was used to explore the acceptability of integrating meditation into outpatient CVD programs and the organisational factors that may affect its integration. Clinicians were recruited through purposive and snowball sampling. E-mail addresses were obtained from publicly listed profiles of cardiovascular and relevant health organisations. Interview questions included perspectives of organising or delivering meditation within a health setting, format of meditation delivery, organisational or other factors that facilitate or present barriers to integrating meditation into clinical practice, and perceived risks associated with integrating meditation in clinical settings. Verbatim transcripts were thematically analysed using an inductive approach and the Braun and Clarke (2006) method to identify themes within barriers and facilitators to implementation. Eighteen predominately female (61%) senior nursing and medical professionals (61%), as well as health managers (17%), psychologists (11%) and allied health professionals (11%), aged 40-60 years were interviewed between 18 May 2017 and 29 March 2018 in Australia via telephone, or face-to-face at a university or the participants' workplace. Three key themes were identified including: enhancing awareness of meditation within a biomedical model of care, building the evidence for meditation in CVD and finding an organisational fit for meditation in cardiovascular care. Meditation was perceived to sit outside the existing health service structure, which prioritised the delivery of medical care. Health professionals perceived that some physicians did not recognise the potential for meditation to improve cardiovascular outcomes while others acknowledged meditation's positive benefits as a safe, low-cost strategy. The benefits of meditation were perceived as subjective, based on preliminary evidence. Health professionals perceived that aligning meditation with health organisational objectives and integrating meditation into outpatient cardiac rehabilitation and community-based secondary prevention pathways is needed. A fully powered clinical trial is required to strengthen the evidence regarding the role of meditation for psychological health in CVD. Generating clinician engagement and support is necessary to enhance awareness of meditation's use in cardiovascular secondary prevention.

Improving the methods for patient-reported experience measures in palliative care: findings from a cognitive interview study.

BACKGROUND: Patient-reported experience measures (PREMs) are questionnaires that ask patients about their experience of healthcare to inform service improvements. It is unclear how palliative care patients manage the cognitive demands of completing PREMs, or how this can best be supported. This study aimed to explore cognitive operations among people with palliative care needs when completing a PREM focused on the care domains known to be important to this patient population in order to inform future administration of questionnaires for this purpose. METHODS: A qualitative approach was taken, using cognitive interviews. Participants were people receiving specialist palliative care with stable disease who were not bedbound. Interviews used 'think aloud' and verbal probes to explore the cognitive operations of comprehension, recall, judgement and response to a 33-item PREM, drafted using a standard process employed by the New South Wales Bureau of Health Information. Analysis proceeded first within- and then cross-cases to explore patterns. RESULTS: Fifteen people participated, all of whom had cancer except one with motor neuron disease. Six discussed inpatient care, and nine community care. Participants encountered challenges with all four cognitive operations. Many participants were unfamiliar with end-of-life care concepts like declining treatment and advance care planning. Participants often struggled to remember, answered hypothetically, or digressed beyond the focal setting. Few participants used the mid-point on a 3-point scale. However, all participants could complete two open-ended items on care aspects they regarded as 'best' or 'most needs improving'. CONCLUSIONS: Palliative care patients find PREMs challenging to complete and require supports to improve the quality and interpretability of data. Pending further research, tentative suggestions are made for PREM design and administration for this patient population.

Patients', caregivers' and clinicians' understandings of an advance care planning process: the example of ambulance palliative care plans.

BACKGROUND: With the introduction of New South Wales Ambulance Authorised Palliative Care Plans within a metropolitan palliative care service, the perspectives of patients, caregivers and clinicians and their understandings of the processes involved in completing the Plans were investigated. METHODS: This qualitative sub-study used semi-structured interviews. Nineteen patients and caregivers who had received an Ambulance Palliative Care Plan and 10 clinicians who completed the Plans were interviewed (n=4) or participated in a focus group (n=6). Grounded theory provided theoretical and procedural direction. Thematic content analysis utilized the constant comparative method. RESULTS: Thematic analysis of patient/caregiver interviews revealed four major themes (I) a lack of involvement in signing the Plan; (II) a need for clear communication about the Plan; (III) trust in the handing over of difficult decisions to family; and (IV) control over where to receive end of life care. Patients indicated that they had little understanding or memory of what the document was or of its purpose, and there were some significant caregiver anxieties about the Plans. Those who were clear on the rationale for the Ambulance Palliative Care Plan demonstrated more prognostic awareness about their condition and the benefits or burdens of resuscitation and treatment. Clinicians identified the main benefit as avoidance of Emergency Department (ED) admission and for patients to be able to choose their preferred place of death. Barriers were mainly systemic and included a lack of clarity around the signature processes and the early implementation of the Plan where the palliative care service was new to patients and families. CONCLUSIONS: The Ambulance Palliative Care Plans are a complex intervention that are sometimes misunderstood by patients, particularly those who are very unwell or who have little prognostic awareness. Clinicians perceive the major benefit to be avoidance of admission to the emergency department.

Thyroid Storm in a Patient With COVID-19.

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19. METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed. RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with proptosis and chemosis, tachycardia, diffusely enlarged goiter with bruit, and fine tremor. Laboratory results demonstrated a thyroid-stimulating hormone level of <0.01 mIU/L (normal range [NR], 0.44-5.3 mIU/L), free thyroxine level of 5.34 ng/dL (NR, 0.64-1.42 ng/dL), total triiodothyronine level of 654 ng/dL (NR, 87-178 ng/dL), and thyroid-stimulating immunoglobulin level of 7.18 IU/L (NR, 0.00-0.55 IU/L). Thyroid ultrasound revealed heterogeneous echotexture with increased vascularity. Nasopharyngeal COVID-19 testing was positive. She was treated promptly with propranolol, propylthiouracil, and hydrocortisone with improvement in symptoms, and later switched to methimazole. Her COVID-19 course was uncomplicated, and she left the hospital with minimal respiratory symptoms. CONCLUSION: Thyroid storms are one of the more prevalent endocrine emergencies and are often precipitated by acute events including infections. Patients with thyroid storms may have concomitant SARS-CoV-2 infection that could influence the clinical course and severity of the disease. In patients with symptoms of thyrotoxicosis and respiratory symptoms, clinicians should consider performing a COVID-19 test.

Novel N1-substituted 1,3-dihydro-2H-benzimidazol-2-ones as potent non-nucleoside reverse transcriptase inhibitors.

Several N(1)-substituted 1,3-dihydro-2H-benzimidazol-2-ones were synthesized and evaluated as anti-HIV agents. Some of them proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentration as potent non-nucleoside HIV-1 RT inhibitors (NNRTIs) with low cytotoxicity. SAR studies highlighted that the nature of the substituents at N(1) and on the benzene ring of benzimidazolone moiety significantly influenced the anti-HIV activity of this class of potent antiretroviral agents.

Optimal Gender-Specific Strategies for the Secondary Prevention of Heart Disease in Women: A SYSTEMATIC REVIEW.

BACKGROUND: There is a paucity of evidence on gender-specific, individually tailored secondary prevention (cardiac rehabilitation [CR]) services for women with heart disease. Women participate less in CR programs, thus increasing their risk of further cardiac events. This review aims to (1) determine the effectiveness of gender-specific interventions specifically designed for women with heart disease, delivered in outpatient CR settings; and (2) classify key elements of effective CR strategies/models for women with heart disease. METHODS: Using the PRISMA guidelines, this is a systematic review of CR models tailored to women to improve cardiovascular risk. Four databases were searched for randomized controlled trials (RCTs) between January 1974 and July 2017 published in peer-reviewed English language journals. RESULTS: Three RCTs comprising 725 women of gender-specific CR strategies were identified. Significant improvements were found in one-third (1 study) of the included multicomponent CR strategies for outcomes including general health, social functioning, vitality, mental health, depression, and quality of life. CONCLUSION: Further large-scale RCTs are required to replicate positive findings and accurately assess the capacity for gender-specific multicomponent CR programs that incorporate participant-driven collaborative models to moderate psychological risk and improve functional capacity and quality of life for women with heart disease.

Improving evidence based practice in postgraduate nursing programs: A systematic review: Bridging the evidence practice gap (BRIDGE project).

BACKGROUND: The nursing profession has a significant evidence to practice gap in an increasingly complex and dynamic health care environment. OBJECTIVE(S): To evaluate effectiveness of teaching and learning strategies related to a capstone project within a Masters of Nursing program that encourage the development of evidence based practice capabilities. DESIGN: Systematic review that conforms to the PRISMA statement. SAMPLE: Master's Nursing programs that include elements of a capstone project within a university setting. DATA SOURCES/REVIEW METHODS: MEDLINE, CINAHL, Cochrane Database of Systematic Reviews, ERIC and PsycInfo were used to search for RCT's or quasi experimental studies conducted between 1979 and 9 June 2017, published in a peer reviewed journal in English. RESULTS: Of 1592 studies, no RCT's specifically addressed the development of evidence based practice capabilities within the university teaching environment. Five quasi-experimental studies integrated blended learning, guided design processes, small group work, role play and structured debate into Masters of Nursing research courses. All five studies demonstrated some improvements in evidence based practice skills and/or research knowledge translation, with three out of five studies demonstrating significant improvements. CONCLUSIONS: There is a paucity of empirical evidence supporting the best strategies to use in developing evidence based practice skills and/or research knowledge translation skills for Master's Nursing students. As a profession, nursing requires methodologically robust studies that are discipline specific to identify the best approaches for developing evidence-based practice skills and/or research knowledge translation skills within the university teaching environment. Provision of these strategies will enable the nursing profession to integrate the best empirical evidence into nursing practice.

Prevalence and characteristics of Australian women who use prayer or spiritual healing: A nationally representative cross-sectional study.

OBJECTIVES: To determine the prevalence and characteristics of users of prayer or spiritual healing among Australian women aged 31-36 years. DESIGN AND SETTING: This cross-sectional study was conducted as a part of the Australian Longitudinal Study on Women's Health (ALSWH). The sample used in the current sub-study were participants from the 'young' cohort (1973-78) (n=8180) aged between 31 and 36 years. MAIN OUTCOME MEASURE: Use of prayer or spiritual healing RESULTS: Prayer or spiritual healing was used on a regular basis by 20% of women aged between 31 and 36 years in 2009. Women who had symptoms of chronic illnesses (p=0.001), women who had never smoked (p=0.001) and women who used other forms of CAM (p<0.001) were significantly more likely to use prayer or spiritual healing. CONCLUSION: A significant proportion of women use prayer or spiritual healing on a regular basis. Further research is required to better understand their rationale for using prayer or spiritual healing and its perceived impact on health related outcomes and general well-being.

Is energy healing an effective non-pharmacological therapy for improving symptom management of chronic illnesses? A systematic review.

BACKGROUND: Emerging evidence suggests that some people living with non-communicable diseases (NCDs) have integrated energy healing into their self-management strategy, however little is known about its efficacy. PURPOSE: To identify energy healing interventions that impacted positively on the symptom management outcomes for patients living in the community with various NCDs. METHODS: A systematic review of energy healing interventions for the management of non-communicable disease related symptoms, conducted between 01 January 2000 and 21 April 2015, published in an English peer-reviewed journal. This review conforms to the PRISMA statement. RESULTS: Twenty seven studies were identified that evaluated various energy healing interventions involving 3159 participants. Thirteen of the energy healing trials generated statistically significant outcomes. CONCLUSIONS: Energy healing has demonstrated some improvement in illness symptoms, however high level evidence consistently demonstrating efficacy is lacking. Further more robust trials are required to better understand which elements of energy healing interventions are associated with positive outcomes.

Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors.

Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.

Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1 RT.

A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.

Prayer or spiritual healing as adjuncts to conventional care: a cross sectional analysis of prevalence and characteristics of use among women.

OBJECTIVES: To determine the prevalence and characteristics of users of prayer or spiritual healing among women. DESIGN AND SETTING: This cross sectional study was conducted as a part of the Australian Longitudinal Study on Women's Health (ALSWH), a 20-year study that examines various factors affecting women's health and well-being. PARTICIPANTS: The sample used in the current study were women from the 1946-1951 cohort (n=9965) (59-64 years) who were surveyed in 2010. OUTCOME MEASURES: Use of prayer or spiritual healing; demographic factors and measures of health status. χ(2) Tests, analyses of variance (to determine associations) and a stepwise backward logistic regression model (for the most significant predictors) using a likelihood ratio test were used to determine the outcome measures. RESULTS: It is estimated that 26% of Australian women from the 1946-1951 cohort (aged 59-64 years) use prayer or spiritual healing on a regular basis. Women were significantly more likely to use prayer or spiritual healing if they were non-smokers, non-drinkers or low-risk drinkers, had symptoms of severe tiredness (OR 1.25; 95% CI 1.12 to 1.40), depression, (OR 1.30; 95% CI 1.11 to 1.53), anxiety (OR 1.33; 95% CI 1.15 to 1.53), diagnosed cancer (OR 1.84; 95% CI 1.28 to 2.65) or other major illnesses (OR 1.43; 95% CI 1.18 to 1.75) and used other complementary therapies. CONCLUSIONS: A significant proportion of adult women are using prayer or spiritual healing. Given that prayer or spiritual healing was significantly associated with health symptoms, chronic illnesses and positive health seeking behaviours, respect for prayer or spiritual healing practices is required within health care settings. Future research is recommended around specific populations using prayer or spiritual healing, reasons for their use and potential benefits on health related outcomes and general well-being.

Design, synthesis, and 3D QSAR of novel potent and selective aromatase inhibitors.

The design, synthesis, and biological evaluation of a series of new aromatase inhibitors bearing an imidazole or triazole ring linked to a fluorene (A), indenodiazine (B), or coumarin scaffold (C) are reported. Properly substituted coumarin derivatives displayed the highest aromatase inhibitory potency and selectivity over 17-alpha-hydroxylase/17-20 lyase. The modeling of the aromatase inhibition data by Comparative Molecular Field Analysis (CoMFA/GOLPE 3D QSAR approach) led to the development of a PLS model with good fitting and predictive powers (n = 22, ONC = 3, r(2) = 0.949, s = 0.216, and q(2) = 0.715). The relationship between aromatase inhibition and the steric and electrostatic fields generated by the examined azole inhibitors enables a clear understanding of the nature and spatial location of the main interactions modulating the aromatase inhibitory potency.

Design, synthesis, structure-activity relationships, and molecular modeling studies of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV agents.

Starting from 1H,3H-thiazolo[3,4-a]benzimidazoles (TBZs), we performed the design, synthesis, and the structure-activity relationship studies of a series of 2,3-diaryl-1,3-thiazolidin-4-ones. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations with minimal cytotoxicity, thereby acting as nonnucleoside HIV-1 RT inhibitors (NNRTIs). Computational studies were used to delineate the ligand-RT interactions and to probe the binding of the ligands to HIV-1 RT.

Synthesis and anti-hIV activity of 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole structurally-related 1,2-substituted benzimidazoles.

The synthesis of 1,2-substituted benzimidazoles is reported. These novel derivatives share chemical similarities with 1-aryl-1H,3H-thiazolo[3,4-a]benzimidazoles, a class of HIV-1 NNRTIs studied widely. All compounds prepared were tested in MT-4 cells to explore their potential anti-HIV activity and were found to be less potent than 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (TBZ).

Synthesis and anti-HIV activity of 2,3-diaryl-1,3-thiazolidin-4-ones.

Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a variously substituted phenyl ring at N-3 have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication.