Fear of cancer recurrence following allogeneic haematopoietic stem cell transplantation (HSCT) for haematological malignancy: A cross-sectional study.

PURPOSE: The aim of this study was to quantify the prevalence of Fear of Cancer Recurrence (FCR) in patients with a prior haematology malignancy surviving more than one year post allogeneic haematopoietic stem cell transplantation (HSCT), and to identify the demographic, medical and psychological factors associated with FCR occurrence. METHOD: Participants were adult allogeneic HSCT recipients who had undergone the procedure for acute leukaemia or other haematological malignancy between the years 2000-2012 in Sydney, Australia. They completed a purpose designed survey and six other validated instruments which assessed FCR, psychological functioning, quality of life, demographic, social and clinical variables. RESULTS: Of the 364 respondents, approximately 11% of the sample lived with severe FCR while only 5% of subjects reported having no FCR. Variables significantly associated with higher FCR included unemployment, a shorter time (years) post-transplant, not attending to health screening (PAP smear), a secondary diagnosis of skin cancer, younger age, referral to a psychiatrist and taking psychotropic medication. Higher psychological distress (depression, anxiety, stress) and lower quality of life made a significant contribution to the prediction of FCR. CONCLUSIONS: Post HSCT follow-up care should include an assessment and discussion regarding FCR to balance both realistic and unrealistic cancer recurrence risks. Managing FCR is one of the most ubiquitous unmet needs of survivors of haematological disease and it is important that HSCT nurses are both aware of the fear, and are equipped with knowledge on how to help patients navigate it with realistic expectations.

A survey of infectious diseases and vaccination uptake in long-term hematopoietic stem cell transplant survivors in Australia.

BACKGROUND: This cross-sectional survey aimed to establish the prevalence of infectious diseases and vaccination uptake in long-term allogeneic hematopoietic stem cell transplants (HSCT) survivors in New South Wales, in order to reduce long-term post-HSCT morbidity and mortality and enhance long-term care. PATIENTS AND METHODS: Hematopoietic stem cell transplants survivors aged over 18 years and transplanted between 2000-2012 in New South Wales (NSW) were eligible to participate. Survivors self-completed the Sydney Post BMT Study survey, FACT-BMT (V4), Chronic Graft versus Host Disease (cGVHD) Activity Assessment Self Report, Lee Chronic GvHD Symptom Scale, DASS21, Post Traumatic Growth Inventory, and the Fear of Recurrence Scale. RESULTS: Of the 583 HSCT survivors contacted, 441 (78%) completed the survey. Respondents included 250 (57%) males and median age was 54 years (range 19-79 years). The median age at the time of transplant was 49 years (Range: 17-71), the median time since HSCT was 5 years (Range: 1-14) and 69% had cGVHD. Collectively, 41.7% of survivors reported a vaccine preventable disease (VPD) with the most common being influenza-like-illness (38.4%), varicella zoster/shingles (27.9%), pap smear abnormalities (9.8%), pneumococcal disease (5.1%), and varicella zoster (chicken pox) (4.6%). Only 31.8% had received the full post-HSCT vaccination schedule, and the majority (69.8%) of these had received the vaccines via their General Practitioner. cGVHD was not found to be a significant factor on multivariate analysis for those who were vaccinated. There was a trend toward lower vaccination rates in patients in a lower income strata. CONCLUSIONS: Vaccinating post-HSCT survivors to prevent infections and their consequences have an established role in post-HSCT care. Improving rates of post-HSCT vaccination should be a major priority for BMT units.

Nutritional issues and body weight in long-term survivors of allogeneic blood and marrow transplant (BMT) in NSW Australia.

PURPOSE: The aims of this study were to describe the long-term nutrition, body weight and body image issues facing survivors of Allogeneic Blood and Marrow Transplant (BMT) and their impact on quality of life. It also describes survivors' perception of enteral feeding during BMT. METHODS: Four hundred and forty-one survivors who had undergone a BMT in NSW, Australia between 2000 and 2012 (n = 441/583) completed the Sydney Post BMT Study Survey (SPBS). RESULTS: Forty-five percent of survivors less than 2-year post-transplant reported a dry mouth, 36 % reported mouth ulcers and 19 % had diarrhoea. This was consistent across all survivor groups, regardless of time since transplant. Patients with one or more gastrointestinal (GI) symptoms had significantly lower quality of life scores. There was a significant difference in quality of life scores when comparing those with no GI symptoms to those with one or more symptoms (P = <0.0001). Quality of life was significantly higher in those who once again enjoyed mealtimes (P < 0.0001). Males were more likely to be satisfied with their body weight compared to females (P = 0.009). The median body mass index (BMI) for all patients reporting body weight satisfaction was significantly lower (BMI 23.5) than those reporting dissatisfaction (BMI 27.5) (P = <0.0001). Survivors who had a normal BMI had significantly higher rates of body weight satisfaction compared to underweight, overweight and obese survivors (P = <0.0001). Those survivors who were overweight or obese were significantly more likely to be diabetic (P = 0.008). CONCLUSION: This study revealed an important relationship between gastrointestinal symptoms, body weight and body image and survivor's quality of life. It provides further support for the importance of nutrition therapy post-BMT.

Haematopoietic stem cell transplantation survivorship and quality of life: is it a small world after all?

PURPOSE: The aim of this qualitative study was to gain a rich understanding of the impact that haematopoietic stem cell transplantation (HSCT) has on long-term survivor's quality of life (QoL). METHOD: Participants included 441 survivors who had undergone HSCT for a malignant or non-malignant disease. Data were obtained by a questionnaire positing a single open-ended question asking respondents to list the three issues of greatest importance to their QoL in survivorship. Responses were analysed and organised into QoL themes and subthemes. RESULTS: Major themes identified included the following: the failing body and diminished physical effectiveness, the changed mind, the loss of social connectedness, the loss of the functional self and the patient for life. Each of these themes manifests different ways in which HSCT survivor's world and opportunities had diminished compared to the unhindered and expansive life that they enjoyed prior to the onset of disease and subsequent HSCT. CONCLUSIONS: HSCT has a profound and pervasive impact on the life of survivors-reducing their horizons and shrinking various parts of their worlds. While HSCT survivors can describe the ways in which their life has changed, many of their fears, anxieties, regrets and concerns are existential in nature and are ill-defined-making it exceeding unlikely that they would be adequately captured by standard psychometric measures of QoL post HSCT.

Epidemiology of complementary and alternative medicine therapy use in allogeneic hematopoietic stem cell transplant survivorship patients in Australia.

In addition to prescribed conventional medicines, many allogeneic hematopoietic stem cell transplant (HSCT) survivors also use complementary and alternative medical therapies (CAM), however, the frequency and types of CAMs used by allogeneic HSCT survivors remain unclear. Study participants were adults who had undergone an allogeneic HSCT between 1st January 2000 and 31st December 2012. Participants completed a 402-item questionnaire regarding the use of CAM, medical complications, specialist referrals, medications and therapies, infections, vaccinations, cancer screening, lifestyle, and occupational issues and relationship status following stem cell transplantation. A total of 1475 allogeneic HSCT were performed in the study period. Of the 669 recipients known to be alive at study sampling, 583 were contactable and were sent study packs. Of 432 participants who returned the completed survey (66% of total eligible, 76% of those contacted), 239 (54.1%) HSCT survivors used at least one form of CAM. These included dietary modification (13.6%), vitamin therapy (30%), spiritual or mind-body therapy (17.2%), herbal supplements (13.5%), manipulative and body-based therapies (26%), Chinese medicine (3.5%), reiki (3%), and homeopathy (3%). These results definitively demonstrate that a large proportion of HSCT survivors are using one or more form of CAM therapy. Given the potential benefits demonstrated by small studies of specific CAM therapies in this patient group, as well as clearly documented therapies with no benefit or even toxicity, this result shows there is a large unmet need for additional studies to ascertain efficacy and safety of CAM therapies in this growing population.

Adherence to cancer screening guidelines in Australian survivors of allogeneic blood and marrow transplantation (BMT).

Allogeneic Blood and Marrow Transplant (BMT) survivors are at high risk of secondary cancers. Although current guidelines endorse survivors following Country-specific general population screening recommendations to mitigate this risk, little is known about cancer screening adherence in Australian BMT survivors. We conducted a cross-sectional survey of 441 BMT survivors who were >1 year post transplant, to explore rates of screening for secondary cancers and to identify barriers to cancer screening recommendations. Survey instruments included the Sydney Post-BMT Survey, FACT-BMT, DASS 21, The Chronic Graft versus Host Disease (GVHD) Activity Assessment-Patient Self-Report (Form B), the Lee Chronic GVHD Symptom Scale, Fear of Cancer Recurrence Scale, and The Post Traumatic Growth Inventory. Fifty-seven percent of respondents were male, median age 54 years, and 40% were >6 years post-BMT. Rates of cancer screening adherence were as follows: cervical 63.4%, breast 53.3%, skin 52.4%, and bowel 32.3%. Older BMT survivors and those >2 years post transplant were more likely to undergo cancer screening. Improved quality of life was associated with screening for skin, breast, and cervical cancer. Fear of cancer recurrence negatively impacted on cervical screening. For those who had not undergone screening, the majority reported not being advised to do so by their treatment team. This study is the largest and most comprehensive to date exploring cancer screening adherence in BMT survivors in Australia. These data provide the basis for health service reform to better meet the needs of BMT survivors and provide evidence to support counseling and education of both patients and professionals.

A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia.

Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61·6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3·3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10·3% reporting success. This study is the largest to date exploring sexual function in survivors of allo-HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre- and post-transplant.

What They Want: Inclusion of Blood and Marrow Transplantation Survivor Preference in the Development of Models of Care for Long-Term Health in Sydney, Australia.

Four hundred forty-one adult allogeneic blood and marrow transplantation (BMT) survivors participated in a cross-sectional survey to assess long-term follow-up (LTFU) model of care preference. Survey instruments included the Sydney Post BMT Survey, Functional Assessment of Cancer Therapy-BMT, Depression Anxiety Stress Scales 21, the Chronic GVHD Activity Assessment-Patient Self Report (Form B), the Lee Chronic GVHD Symptom Scale and the Post-Traumatic Growth Inventory. We found most BMT survivors (74%) would prefer LTFU with their transplantation physicians alone or in combination with transplantation center-linked services (satellite clinics or telemedicine) Over one-quarter indicated a preference for receiving comprehensive post-transplantation care in a "satellite" clinic staffed by their BMT team situated closer to their place of residence, with higher income, higher educational level, and sexual morbidity being significant social factors influencing this preference. Regular exercise was reported less often in those who preferred telemedicine, which may reflect reduced mobility. The factor most strongly associated with a preference for transplantation center follow-up was the severity of chronic graft-versus-host disease. Full- and part-time work were negatively associated with transplantation center follow-up, possibly implying decreased dependency on the center and some return to normalcy. This study is the first to explore the preferences of BMT survivors for long-term post-transplantation care. These data provides the basis for LTFU model of care development and health service reform consistent with the preferences of BMT survivors.

New insights into the analysis of the electrode kinetics of flavin adenine dinucleotide redox center of glucose oxidase immobilized on carbon electrodes.

New insights into electrochemical kinetics of the flavin adenine dinucleotide (FAD) redox center of glucose-oxidase (GlcOx) immobilized on reduced graphene oxide (rGO), single- and multiwalled carbon nanotubes (SW and MWCNT), and combinations of rGO and CNTs have been gained by application of Fourier transformed AC voltammetry (FTACV) and simulations based on a range of models. A satisfactory level of agreement between experiment and theory, and hence establishment of the best model to describe the redox chemistry of FAD, was achieved with the aid of automated e-science tools. Although still not perfect, use of Marcus theory with a very low reorganization energy (≤0.3 eV) best mimics the experimental FTACV data, which suggests that the process is gated as also deduced from analysis of FTACV data obtained at different frequencies. Failure of the simplest models to fully describe the electrode kinetics of the redox center of GlcOx, including those based on the widely employed Laviron theory is demonstrated, as is substantial kinetic heterogeneity of FAD species. Use of a SWCNT support amplifies the kinetic heterogeneity, while a combination of rGO and MWCNT provides a more favorable environment for fast communication between FAD and the electrode.

The effect of endotracheal tube size on voice and swallowing function in patients with thermal burn injury: an evaluation using the Australian Therapy Outcome Measures (AusTOMS).

The objective of this study was to determine if intubation using larger endotracheal tube sizes in mechanically ventilated patients with thermal burn injury adversely affects voice and swallowing function. This prospective, observational study was conducted in patients with thermal burn injuries, who were mechanically ventilated via an endotracheal tube. The primary outcome measures were changes in voice and swallowing function, assessed using the Australian Therapy Outcome Measures (AusTOMS), immediately before the burn injury, and 12 months after the removal of the endotracheal tube. Of 101 patients screened, 20 male patients were followed for 12 months. Patients intubated with size 8.0 or larger endotracheal tubes were compared to patients with size 7.5 endotracheal tubes or smaller. Patients with the larger endotracheal tubes had a significant 1.8-point (9%) decline in their AusTOMS voice score (p =.01) using the paired t-test, but there was no significant difference between the two groups using the independent samples t-test. There was no significant difference in swallowing outcome between the two groups. Male patients with thermal burn injuries, mechanically ventilated using size 8.0 endotracheal tubes or larger, had a statistically significant decline in voice outcome; however, interpretation of this result is limited by methodological considerations.

Expansion of a medical emergency team system to a mental health facility.

BACKGROUND: Clinical emergency response systems such as medical emergency teams (MET) are used in many hospitals worldwide, but the effect that these systems have in mental health facilities is unknown. This study examined the rate and nature of MET calls to a mental health facility that had relocated to the campus of a tertiary referral hospital. METHODS: This study was a prospective, observational study of MET calls to a newly constructed 170 bed mental health facility. Data were collected on the number and nature of MET calls to the facility. RESULTS: Over 24 months, there were 66 MET calls to the mental health facility, and 1217 MET calls at the main hospital. The mean MET call rate was 14.2 calls per 1000 admissions (95% confidence interval (CI) 10.8-17.7) at the mental health facility, and 14.7 calls per 1000 admissions (95% CI 13.9-15.5) at the main hospital. Neurological and cardiovascular problems were present in 61% and 41% of MET calls. CONCLUSION: The rate of MET calls to a new mental health facility can be similar to that of a tertiary hospital. Staff attending MET calls need to be prepared to manage predominantly neurological and cardiovascular problems.

Palliative care teams in the intensive care unit: a randomised, controlled, feasibility study.

OBJECTIVES: To determine whether palliative care teams can improve patient, family and staff satisfaction for patients receiving end-of-life care in the intensive care unit and reduce surrogate markers of health care costs. DESIGN: Randomised controlled, feasibility study. SETTING: 14-bed general ICU over 29 months in 2006-2008. PARTICIPANTS: Patients admitted with a terminal or preterminal condition, for whom the treating intensivist considered that escalating or continuing treatment was unlikely to achieve significant improvement in the patient's clinical condition. INTERVENTION: A consultation from a palliative care team, in addition to usual ICU end-of-life care. MAIN OUTCOME MEASURES: ICU and hospital length of stay, and changes in composite scores of satisfaction obtained from questionnaires administered to families, nursing staff and intensivists. RESULTS: The study was constrained by significant logistical and methodological problems, including low recruitment and questionnaire completion rates, and the lack of an available validated questionnaire. From a total of 2009 admissions over a 29-month period, 20 patients were enrolled, 10 in each group. There were significant differences in baseline characteristics. There were no statistically significant differences between those who had a consultation with the palliative care team and those who did not in median ICU length of stay (3 days v 5 days, P=0.97), median hospital length of stay (5 days v 11 days, P=0.44), or changes in overall composite satisfaction scores reported by families (-6% v -6%, P=0.91), nursing staff (+5% v +15%, P=0.30), and intensivists (-2% v +2%, P=0.42). CONCLUSION: This feasibility study was difficult to conduct and did not generate any robust conclusions about the utility of involving palliative care teams in end-of-life care in the ICU. Larger studies are technically possible but unlikely to be feasible. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN012606000110583.

Injuries occurring in hospital staff attending medical emergency team (MET) calls--a prospective, observational study.

BACKGROUND: Clinical emergency response systems such as medical emergency teams (MET) have been implemented in many hospitals worldwide, but the effect that these systems have on injuries to hospital staff is unknown. The objective of this study was to determine the rate and nature of injuries occurring in hospital staff attending MET calls. METHODS: This study was a prospective, observational study, using a structured interview, of 1265 MET call participants, in a 650 bed urban, teaching hospital. Data was collected on the number and the nature of injuries occurring in hospital staff attending MET calls. RESULTS: Over 131 days, 248 MET calls were made. An average of 8.1 staff participated in each MET call. The overall injury rate was 13 (95% confidence interval (CI) 7-20) per 1000 MET participant attendances, and 70 (95% CI 38-102) per 1000 MET calls. One injured participant required time off-work, an injury requiring time off-work rate of 1 (95% CI 0-4) per 1000 MET participant attendances, or 4 (95% CI 0-27) per 1000 MET calls. The relative risk of sustaining an injury if the MET participant performed chest compressions, contacted patient body fluids on clothing or protective equipment, without direct contact to skin or mucosa, or lifted the patient or a patient body part was 11.0 (95% CI 4.2-28.6), 8.7 (95% CI 3.4-22.0) and 5.5 (95% CI 2.1-14.2), respectively. CONCLUSION: The rate of injuries occurring to hospital staff attending MET calls is relatively low, and many injuries could be considered relatively minor.

Does experience in colposcopy improve identification of high grade abnormalities?

OBJECTIVE: This study investigates whether experience in colposcopy improves identification of high grade abnormalities. The sensitivity and positive predictive value (PPV) of colposcopy in identifying high grade intra-epithelial lesions (HSIL) performed by relatively inexperienced as compared to experienced colposcopists are evaluated. STUDY DESIGN: Of 18,421 colposcopies performed at the Royal Women's Hospital, Melbourne, Australia, between 1999 and 2004 by 5 senior and 11 junior colposcopists, the colposcopic impression was correlated with the histopathology result of the biopsy taken at 6020 colposcopies, with respect to the experience of the colposcopist. RESULTS: Colposcopy had a 60% sensitivity and 60% PPV in identifying HSIL in this study. In case of a high-grade referral smear the sensitivity and PPV in identifying HSIL were, respectively 76% and 73%, compared with 26% and 48% in case of a low-grade referral smear, no difference in overall colposcopic performance between experienced and inexperienced colposcopists was observed. However, the sensitivity of identifying HSIL was significantly higher with inexperienced colposcopists, and the PPV was significantly higher with experienced colposcopists. CONCLUSION: In this study experience did not improve colposcopic performance, but differences in colposcopic strategy between the two groups were noted. The rather low overall sensitivity and PPV of colposcopy in identifying HSIL, especially in case of a low-grade referral smear, indicate that the role of colposcopy in the detection and treatment of cervical abnormalities is to assess size, site, and extent of an abnormality, rather than to assess the severity of this abnormality. Histology must remain the gold standard for treatment.

Intrasplicing coordinates alternative first exons with alternative splicing in the protein 4.1R gene.

In the protein 4.1R gene, alternative first exons splice differentially to alternative 3' splice sites far downstream in exon 2'/2 (E2'/2). We describe a novel intrasplicing mechanism by which exon 1A (E1A) splices exclusively to the distal E2'/2 acceptor via two nested splicing reactions regulated by novel properties of exon 1B (E1B). E1B behaves as an exon in the first step, using its consensus 5' donor to splice to the proximal E2'/2 acceptor. A long region of downstream intron is excised, juxtaposing E1B with E2'/2 to generate a new composite acceptor containing the E1B branchpoint/pyrimidine tract and E2 distal 3' AG-dinucleotide. Next, the upstream E1A splices over E1B to this distal acceptor, excising the remaining intron plus E1B and E2' to form mature E1A/E2 product. We mapped branchpoints for both intrasplicing reactions and demonstrated that mutation of the E1B 5' splice site or branchpoint abrogates intrasplicing. In the 4.1R gene, intrasplicing ultimately determines N-terminal protein structure and function. More generally, intrasplicing represents a new mechanism by which alternative promoters can be coordinated with downstream alternative splicing.

High frequency of alternative first exons in erythroid genes suggests a critical role in regulating gene function.

The human genome uses alternative pre-mRNA splicing as an important mechanism to encode a complex proteome from a relatively small number of genes. An unknown number of these genes also possess multiple transcriptional promoters and alternative first exons that contribute another layer of complexity to gene expression mechanisms. Using a collection of more than 100 erythroid-expressed genes as a test group, we used genome browser tools and genetic databases to assess the frequency of alternative first exons in the genome. Remarkably, 35% of these erythroid genes show evidence of alternative first exons. The majority of the candidate first exons are situated upstream of the coding exons, whereas a few are located internally within the gene. Computational analyses predict transcriptional promoters closely associated with many of the candidate first exons, supporting their authenticity. Importantly, the frequent presence of consensus translation initiation sites among the alternative first exons suggests that many proteins have alternative N-terminal structures whose expression can be coupled to promoter choice. These findings indicate that alternative promoters and first exons are more widespread in the human genome than previously appreciated and that they may play a major role in regulating expression of selected protein isoforms in a tissue-specific manner.

Evolutionarily conserved coupling of transcription and alternative splicing in the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes.

Recent studies have shown that transcription and alternative splicing can be mechanistically coupled. In the EPB41 (protein 4.1R) and EPB41L3 (protein 4.1B) genes, we showed previously that promoter/alternative first exon choice is coupled to downstream splicing events in exon 2. Here we demonstrate that this coupling is conserved among several vertebrate classes from fish to mammals. The EPB41 and EPB41L3 genes from fish, bird, amphibian, and mammal genomes exhibit shared features including alternative first exons and differential splice acceptors in exon 2. In all cases, the 5'-most exon (exon 1A) splices exclusively to a weaker internal acceptor site in exon 2, skipping a fragment designated as exon 2'. Conversely, alternative first exons 1B and 1C always splice to the stronger first acceptor site, retaining exon 2'. These correlations are independent of cell type or species of origin. Since exon 2' contains a translation initiation site, splice variants generate protein isoforms with distinct N-termini. We propose that these genes represent a physiologically relevant model system for mechanistic analysis of transcription-coupled alternative splicing.

Potassium bromide, an anticonvulsant, is effective at alleviating seizures in the Drosophila bang-sensitive mutant bang senseless.

Human seizure disorders are a major health concern due to the large number of affected individuals, the potentially devastating consequences of untreated seizure occurrences, and the lack of an effective treatment for all patients. Although anticonvulsants have proven very helpful in treating seizures and remain the best option available for treatment, not all afflicted individuals respond to medication and many only do so in unique drug combinations or at the cost of adverse side-effects. Therefore, new and more effective anticonvulsants are continually sought after to combat this illness. In this study, we present results which offer the possibility of using Drosophila bang-sensitive (BS) mutants as a tool to screen anticonvulsants. By feeding the BS mutants a known anticonvulsant, potassium bromide, we have demonstrated that the drug dramatically reduces the seizures of bang senseless, the most severe of the BS mutants. This methodology suggests that the Drosophila system can potentially be a powerful instrument for assaying and testing new compounds with anticonvulsant properties.