A systematic review of qualitative research exploring patient and health professional perspectives of breakthrough cancer pain.

PURPOSE: Breakthrough cancer pain (BtCP) is a prevalent health issue which is difficult to manage. A plethora of quantitative research in this area exists. There is a paucity of research on the perspectives of health professionals and patients surrounding domains impacting effective treatment, including definitions of BtCP, treatment, and education opportunities. This review aims to identify and synthesize the extent of qualitative research exploring health professional and patient perspectives of BtCP. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was undertaken. The approach was registered with Prospero. MEDLINE, EMBASE, and Web of Science were searched for peer-reviewed literature published any date prior to May 19, 2022. Eligible sources must have considered health professional and/or patient perspectives of BtCP. A narrative synthesis approach was utilized. RESULTS: Three sources met the review criteria. One source explored nurse perspectives, while two sources explored patient perspectives. Study quality was moderate to high. Overlapping themes across the three studies included communication, defining BtCP, impact of BtCP, management of BtCP, perceptions of BtCP, analgesia and pain relief, and training and professional development. CONCLUSION: Given limited research investigating clinician and patient perspectives of BtCP, a rich understanding informed by exploratory qualitative methods around identification, best management strategies, professional development, and factors promoting and inhibiting best practice remains unclear. Further qualitative inquiry is warranted, and it is expected such research will inform BtCP clinical guidelines.

In vitro fertilisation/intracytoplasmic sperm injection beyond 2020.

Over 8 million babies have been born following IVF (in vitro fertilisation) and other artificial reproductive technology (ART) procedures since Louise Brown's birth 40 years ago. New innovations have added much complexity to both clinical and laboratory procedures over the last four decades. Translation of novel approaches from basic science into clinical practice continues unabated, widening the applicability of ART to new groups of people and helping improve both chances of healthy live birth and patient acceptability. However, the impact of ART on the health of both patients and their offspring continues to cause concern, and many ethical challenges created by new scientific developments in this field attract widely differing opinions. What is undeniable is that there will be a sustained global growth in utilisation of ART and that reproductive tourism will allow many people to access the treatment they desire notwithstanding national regulations that may forbid some approaches. The greatest challenge is to expand access to ART to those living in the less wealthy nations who are equally deserving of its benefits.

Post-traumatic stress disorder dimensions and asthma morbidity in World Trade Center rescue and recovery workers.

OBJECTIVE: Using data from a cohort of World Trade Center (WTC) rescue and recovery workers with asthma, we assessed whether meeting criteria for post-traumatic stress disorder (PTSD), sub-threshold PTSD, and for specific PTSD symptom dimensions are associated with increased asthma morbidity. METHODS: Participants underwent a Structured Clinical Interview for Diagnostic and Statistical Manual to assess the presence of PTSD following DSM-IV criteria during in-person interviews between December 2013 and April 2015. We defined sub-threshold PTSD as meeting criteria for two of three symptom dimensions: re-experiencing, avoidance, or hyper-arousal. Asthma control, acute asthma-related healthcare utilization, and asthma-related quality of life data were collected using validated scales. Unadjusted and multiple regression analyses were performed to assess the relationship between sub-threshold PTSD and PTSD symptom domains with asthma morbidity measures. RESULTS: Of the 181 WTC workers with asthma recruited into the study, 28% had PTSD and 25% had sub-threshold PTSD. Patients with PTSD showed worse asthma control, higher rates of inpatient healthcare utilization, and poorer asthma quality of life than those with sub-threshold or no PTSD. After adjusting for potential confounders, among patients not meeting the criteria for full PTSD, those presenting symptoms of re-experiencing exhibited poorer quality of life (p = 0.003). Avoidance was associated with increased acute healthcare use (p = 0.05). Sub-threshold PTSD was not associated with asthma morbidity (p > 0.05 for all comparisons). CONCLUSIONS: There may be benefit in assessing asthma control in patients with sub-threshold PTSD symptoms as well as those with full PTSD to more effectively identify ongoing asthma symptoms and target management strategies.

The influence of population mobility on changing patterns of HIV acquisition: lessons for and from Australia.

Investment, bipartisan support and involvement from affected communities have characterised Australia's HIV response, and helped maintain a low prevalence epidemic. Patterns of HIV acquisition are changing, with an increasing number of infections acquired overseas by migrant and mobile populations. A coordinated national response is required to address HIV acquisition in the context of population mobility.

Ethics and health promotion practice: exploring attitudes and practices in Western Australian health organisations.

Issue addressed Evidence-informed practice underpinned by ethics is fundamental to developing the science of health promotion. Knowledge and application of ethical principles are competencies required for health promotion practice. However, these competencies are often inconsistently understood and applied. This research explored attitudes, practices, enablers and barriers related to ethics in practice in Western Australian health organisations. Methods Semistructured, in-depth interviews were conducted with 10 health promotion practitioners, purposefully selected to provide a cross-section of government and non-government organisations. Interviews were recorded, transcribed and then themed. Results The majority of participants reported consideration of ethics in their practice; however, only half reported seeking Human Research Ethics Committee (HREC) approval for projects in the past 12 months. Enablers identified as supporting ethics in practice and disseminating findings included: support preparing ethics applications; resources and training about ethical practice; ability to access HRECs for ethics approval; and a supportive organisational culture. Barriers included: limited time; insufficient resourcing and capacity; ethics approval not seen as part of core business; and concerns about academic writing. Conclusion The majority of participants were aware of the importance of ethics in practice and the dissemination of findings. However, participants reported barriers to engaging in formal ethics processes and to publishing findings. So what? Alignment of evidence-informed and ethics-based practice is critical. Resources and information about ethics may be required to support practice and encourage dissemination of findings, including in the peer-reviewed literature. Investigating the role of community-based ethics boards may be valuable to bridging the ethics-evidence gap.

Unmet needs of people with end-stage chronic obstructive pulmonary disease: recommendations for change in Australia.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an increasing cause of mortality. However, people with COPD are unlikely to receive care that meets the needs of themselves or their carers at the end of life. AIMS: To explore the needs of people with end-stage COPD in South Australia and develop recommendations for a model of care. METHODS: Three related studies were undertaken: in Study 1, 15 people with advanced COPD and their carers were interviewed twice, 6 months apart; Study 2 investigated views of an Expert Panel and Study 3 conducted focus groups and interviews with service providers and community groups to examine service availability and accessibility. RESULTS: This project demonstrated that the needs of people with COPD are not being met. There was an absence of a coordinated pathway for support. Care was fragmented, episodic and reactive. The role of carers was poorly recognised. Health professionals identified the lack of a clear transition to an end-stage and significant barriers to obtaining support for activities of daily living. Communication issues were identified in all studies, including the absence of advance care planning conversations. CONCLUSIONS: A flexible model of care is needed that assists people with COPD to navigate the health system. This should be patient centred and coordinated across primary, acute and community sectors. Neither respiratory nor palliative care services alone can adequately support people with COPD. The integration of a multidisciplinary palliative approach within a chronic disease management strategy will be central for the best care for people living with advanced COPD.

More than mateship: exploring how Australian male expatriates, longer-term and frequent travellers experience social support.

PURPOSE: Those travelling overseas for work or leisure including male expatriates, longer-term and frequent travellers (ELoFTs) may be at heightened risk for a range of health and wellbeing issues. Social support may mediate this risk. However, from a public health perspective, little is written about how ELoFTs access health information and support and the role of their social networks in facilitating health and wellbeing outcomes. This research was part of a study examining social network processes of Australian male ELoFTs travelling, living, or working in Southeast Asia (SEA). METHODS: Symbolic Interactionism and Grounded Theory were the conceptual framework and methodology supporting semi-structured, in-depth interviews (n = 25) conducted in Australia and Thailand with Australian male ELoFTs to SEA, aged 18 years or older. RESULTS: Findings highlight supports that assist ELoFT transition and adjustment to country of destination or manage their transnational experience. Influential places, people, and points in the migration journey mediated engagement with social support. CONCLUSIONS: ELoFT social networks and the support provided within them may provide a mechanism for intervention across a range of public health issues. Findings may support the development of policy and practice across industries charged with supporting successful ELoFT adjustment.

Drinking and swimming around waterways: The role of alcohol, sensation-seeking, peer influence and risk in young people.

The role of individual and sociocultural factors contributing to drowning risk for young adults is complex and poorly understood. This study examined the relationship between behaviour in and around waterways and: 1) alcohol consumption; 2) resistance to peer influence; 3) sensation-seeking; 4) perception of risk among people aged 15-24 in Western Australia. A cross-sectional online survey was conducted at three time-points with a convenience sample. Predictor variables included: Alcohol Use Disorder Identification Test Consumption (AUDIT_C); Resistance to Peer Influence; Brief Sensation Seeking scale; Benthin's Perception of risk. Pearson chi-squared tests determined the association between demographic and predictor variables. Logistic regression explored influence of potential predictor variables on behaviour in and around water. The final sample (n = 730) participants, consisted of females (n = 537, 74.5%), metropolitan dwelling (n = 616, 84.4%), and attended university (n = 410, 56.9%). Significant associations were found for those who swum after drinking alcohol compared with those that had not by age, gender, education. For every 1-unit increase in AUDIT-C participants were 60% more likely to swim after drinking (OR 95% CI 1.60 1.44-1.78). Participants who considered an adverse event serious were 15% less likely to have swum after drinking alcohol (OR 0.85 95% CI 0.73-0.99). The complex relationship between social participation in activities in and around waterways, higher drowning rates, propensity for risk, and the meaning young adults attach to risk locations and practices present unique challenges for drowning prevention research. Findings should be used to improve the awareness and education components of future youth water safety strategies in high-income settings.

Lacticaseibacillus rhamnosus GG DSM 33156 effects on pathogen defence in the upper respiratory tract: a randomised, double-blind, placebo-controlled paediatric trial.

Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward's hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.

Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response.

BACKGROUND: Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. METHOD: An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. RESULTS: The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression-Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). CONCLUSIONS: Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

An investigation of patients' motivations for their participation in genetics-related research.

DESIGN: Qualitative interview study. PARTICIPANTS: Fifty-nine patients with a family history of cancer who attend a regional cancer genetics clinic in the UK were interviewed about their current and previous research experiences. FINDINGS: Interviewees gave a range of explanations for research participation. These were categorised as (a) social--research participation benefits the wider society by progressing science and improving treatment for everyone; (b) familial--research participation may improve healthcare and benefit current or future generations of the participant's family; and (c) personal--research participation provides therapeutic or non-therapeutic benefits for oneself. CONCLUSIONS: We discuss the distinction drawn between motives for research participation focused upon self (personal) and others (familial/social), and observe that personal, social and familial motives can be seen as interdependent. For example, research participation that is undertaken to benefit others, particularly relatives, may also offer a number of personal benefits for self, such as enabling participants to feel that they have discharged their social or familial obligations. We argue for the need to move away from simple, static, individualised notions of research participation to a more complex, dynamic and inherently social account.

Putative 51,000-Mr protein marker for postsynaptic densities is virtually absent in cerebellum.

Cerebrum and cerebellum contain numerous asymmetric synapses characterized by the presence of a postsynaptic thickening prominently stained by phosphotungstic acid and other electron-dense stains suitable for electron microscopy. A 51,000-Mr protein, copurified in postsynaptic density-enriched fractions from cerebrum, is considered to be a well established marker for the postsynaptic density. On the basis of two criteria, our studies demonstrate that the 51,000-Mr protein marker for postsynaptic densities is virtually absent in cerebellum, First, it is present in negligible amounts in deoxycholate-insoluble fractions from cerebellum but abundant in parallel fractions from cerebrum. Secondly, the 51,000-Mr protein, which binds 125I-calmodulin after SDS PAGE is readily visualized in membrane samples from cerebrum but is virtually undetectable in cerebellar samples. It is apparent that these results require reexamination of the role of the 51,000-Mr protein in postsynaptic density structures.

Assembly of the dystrophin-associated protein complex does not require the dystrophin COOH-terminal domain.

Dystrophin is a multidomain protein that links the actin cytoskeleton to laminin in the extracellular matrix through the dystrophin associated protein (DAP) complex. The COOH-terminal domain of dystrophin binds to two components of the DAP complex, syntrophin and dystrobrevin. To understand the role of syntrophin and dystrobrevin, we previously generated a series of transgenic mouse lines expressing dystrophins with deletions throughout the COOH-terminal domain. Each of these mice had normal muscle function and displayed normal localization of syntrophin and dystrobrevin. Since syntrophin and dystrobrevin bind to each other as well as to dystrophin, we have now generated a transgenic mouse deleted for the entire dystrophin COOH-terminal domain. Unexpectedly, this truncated dystrophin supported normal muscle function and assembly of the DAP complex. These results demonstrate that syntrophin and dystrobrevin functionally associate with the DAP complex in the absence of a direct link to dystrophin. We also observed that the DAP complexes in these different transgenic mouse strains were not identical. Instead, the DAP complexes contained varying ratios of syntrophin and dystrobrevin isoforms. These results suggest that alternative splicing of the dystrophin gene, which naturally generates COOH-terminal deletions in dystrophin, may function to regulate the isoform composition of the DAP complex.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.

Healthcare professionals' and researchers' understanding of cancer genetics activities: a qualitative interview study.

AIMS: To describe individuals' perceptions of the activities that take place within the cancer genetics clinic, the relationships between these activities and how these relationships are sustained. DESIGN: Qualitative interview study. PARTICIPANTS: Forty individuals involved in carrying out cancer genetics research in either a clinical (n = 28) or research-only (n = 12) capacity in the UK. FINDINGS: Interviewees perceive research and clinical practice in the subspecialty of cancer genetics as interdependent. The boundary between research and clinical practice is described as vague or blurred, and this ambiguity is regarded as being sustained by a range of methodological, ethical and economic factors. The implications of these findings for the "therapeutic misconception" are explored. It is argued that while research participation is seen as having therapeutic benefit for individual patients, the interviewees are not labouring under any misconceptions about the relationship between research and clinical care. It is suggested that concepts such as the "therapeutic misconception" may have less relevance in highly technological specialities that are characterised by a developing evidence base.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations.

Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was approximately 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.

Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases.

A screen for proteins that interact with beta 2-syntrophin led to the isolation of MAST205 (microtubule-associated serine/threonine kinase-205 kD) and a newly identified homologue, SAST (syntrophin-associated serine/threonine kinase). Binding studies showed that beta 2-syntrophin and MAST205/SAST associated via a PDZ-PDZ domain interaction. MAST205 colocalized with beta 2-syntrophin and utrophin at neuromuscular junctions. SAST colocalized with syntrophin in cerebral vasculature, spermatic acrosomes and neuronal processes. SAST and syntrophin were highly associated with purified microtubules and microtubule-associated proteins, whereas utrophin and dystrophin were only partially associated with microtubules. Our data suggest that MAST205 and SAST link the dystrophin/utrophin network with microtubule filaments via the syntrophins.