A temperature-dependent virus-binding assay reveals the presence of neutralizing antibodies in human cytomegalovirus gB vaccine recipients' sera.

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) - a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations.

Why do men with prostate cancer discontinue active surveillance for definitive treatment? A mixed methods investigation.

OBJECTIVES: To explore the personal and/or medical reasons patients on active surveillance (AS) have, or consider having, further definitive treatment for their prostate cancer. Research suggests up to 50% of patients on AS will discontinue within 5 years, though reasons for discontinuation from the patient's perspective is under-explored. METHODS: Prostate cancer patients who were or had been on AS for at least 6 months were recruited. A questionnaire assessed reasons for receiving/considering definitive treatment and the extent to which reasons were personal or medical. Clinical information was extracted from a state-level population registry. A subset of participants were interviewed to further explore questionnaire responses. RESULTS: One-hundred and-three individuals completed the survey; 33 were also interviewed. Fifty-four survey participants (52%) had discontinued AS for definitive treatment. Common reasons for discontinuation were evidence of disease progression, doctor recommendation, desire to act, and fear of progression. Many participants who considered or had treatment reported weighing medical and personal factors equally in their decision. Interview participants described strongly considering any amount of disease progression and personal factors such as fear of progression, family concerns, and adverse vicarious experiences when deciding whether to pursue treatment. CONCLUSION: Both medical and personal factors are considered when deciding whether to discontinue AS. Identifying predictors of discontinuation is essential for informing supportive care services to improve AS management.

Experiences and needs of people with haematological cancers during the COVID-19 pandemic: A qualitative study.

OBJECTIVE: Haematological cancer patients are particularly vulnerable to the effects of COVID-19. In addition to being immunocompromised, pandemic-related travel restrictions have impacted access to treatments and overseas stem cell donations for patients requiring transplantation. Given this vulnerability, people with haematological cancers are at risk of experiencing heightened distress during the pandemic. This study aimed to explore haematological cancer patients' experiences and needs. METHODS: Twenty-four Australian haematological cancer patients completed semi-structured interviews exploring their concerns and worries during the pandemic, impact of pandemic on management of disease, access to information and support, lifestyle changes, and attitudes towards emerging models of healthcare during the pandemic. Interview transcripts were thematically analysed. RESULTS: Four themes reflecting the experiences of haematological cancer patients during the pandemic were identified: 'Fears about contracting COVID-19' (behaviour changes to protect health, impact on daily routine and habits, annoyance at dismissive attitude of others toward COVID-19); 'Reduced sense of connection and support' (reduced social support and access to external support services); 'New challenges' (increased financial hardship, worsened health), and; 'Underlying system and communication issues' (access to trusted information, satisfaction/dissatisfaction with care, navigating telehealth). Participants expressed a need for improved access to support services and trusted information. CONCLUSIONS: The findings emphasise the additional challenges experienced by haematological cancer patients during the COVID-19 pandemic and their impact on daily life. Results point to the importance of validation of increased distress during periods of uncertainty; reinforcing recommendations about high-quality sources of information; and facilitating access to support services when face-to-face care is limited.

Impact of different unconditional monetary incentives on survey response rates in men with prostate cancer: a 2-arm randomised trial.

BACKGROUND: Men are often viewed as a difficult group to recruit for psychological research, including in psycho-oncology. Whilst research has demonstrated the effectiveness of small monetary incentives for encouraging research participation, little research has examined different large unconditional incentive amounts. Larger unconditional incentives may result in increased participation of men in psychological research. This randomised study within a case-control trial of men diagnosed with early-stage prostate cancer aimed to investigate whether (a) response rates to a 30-min questionnaire completed via mail, online, or phone would vary with different unconditional incentive amounts, and (b) demographics would vary in those who responded within the different incentive groups. METHODS: We conducted this randomised study within a case-control cross-sectional study aiming to identify the social-ecological factors influencing treatment discontinuation in prostate cancer patients. A total of 238 participants from the cross-sectional study were randomised to receive one of two unconditional incentives (n = 121 received AUD$10, n = 117 received AUD$20) with the study materials (consent form and survey). RESULTS: Overall, 113 (47%) responded; n = 61/121 (50.4%) in the AUD$10 group, and n = 52/117 (44.4%) in the AUD$20 group. No evidence of a difference was found in response rates by incentive group (odds ratio 1.27, 95% CI = 0.76-2.12, p = 0.36). Additionally, there were no evident differences in the demographics of the responders vs. non-responders within each incentive group (all p > 0.05). CONCLUSIONS: Unlike previous research, we were unable to show that higher monetary incentives were more effective for increasing response rates. An AUD$20 unconditional incentive may be no more effective than a lesser amount for encouraging prostate cancer survivors to participate in research involving long questionnaires. Future research should consider the cost-benefits of providing large unconditional incentives, as non-responses will result in lost resources perhaps better utilised in other engagement strategies.

Social ecological influences on treatment decision-making in men diagnosed with low risk, localised prostate cancer.

OBJECTIVE: Individuals diagnosed with low risk, localised prostate cancer (PCa) face a difficult decision between active surveillance (AS) and definitive treatment. We aimed to explore perceived influences on treatment decision-making from the patient and partner's perspectives. METHODS: Patients (and partners) who met AS criteria and had chosen their treatment were recruited. Semi-structured individual interviews were conducted via telephone to explore experiences of diagnosis, impact on patient lifestyle, experiences with physicians, treatment preferences/choice, treatment information understanding and needs, and overall decision-making process. Interviews were audio recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. RESULTS: Twenty-four male patients (18 chose AS) and 12 female partners participated. Five themes relating to social-ecological influences on treatment choice were identified: (1) partner support and direct influence on patient treatment choice, (2) patient and partner vicarious experiences may influence treatment decisions, (3) the influence of the patient's life circumstances, (4) disclosing to wider social networks: friends, family, and co-workers, and (5) the importance of a good relationship and experience with physicians. Additionally, two themes were identified relating to information patients and partners received about the treatment options during their decision-making process. CONCLUSIONS: A range of individual and social influences on treatment decision-making were reported. Physicians providing treatment recommendations should consider and discuss the patient and partner's existing beliefs and treatment preferences and encourage shared decision-making. Further research on treatment decision-making of partnered and non-partnered PCa patients is required. We recommend research considers social ecological factors across the personal, interpersonal, community, and policy levels.

IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero-positive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of sero-positive individuals improved pre-existing gB-specific IgA and IgG levels and induced de novo gB-specific IgA and IgG responses in sero-negative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination, but de novo AD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breastmilk samples. All antibodies binding AD-2 contained kappa light chains, whereas balanced kappa/lambda light chain usage was found for those binding to gB. V region-matched AD-2-specific recombinant IgG and IgA bound both to gB and to AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk, which may function to protect neonates from HCMV.

Development and psychometric properties of surveys to assess patient and family caregiver experience with care transitions.

BACKGROUND: The purpose of this study was to develop and administer surveys that assess patient and family caregiver experiences with care transitions and examine the psychometric properties of the surveys. The surveys were designed to ask about 1) the transitional care services that matter most to patients and their caregivers and 2) care outcomes, including the overall quality of transitional care they received, patient self-reported health, and caregiver effort/stress. METHODS: Survey items were developed based on a review of the literature, existing surveys, focus groups, site visits, stakeholder and expert input, and patient and caregiver cognitive interviews. We administered mail surveys with telephone follow up to patients recently discharged from 43 U.S. hospitals. Patients identified the caregivers who helped them during their hospital stay (Time 1 caregiver) and when they were home (Time 2 caregiver). Time 1 and Time 2 caregivers were surveyed by telephone only. The psychometric properties of the survey items and outcome composite measures were examined for each of the three surveys. Items that performed poorly across multiple analyses, including those with low variability and/or a high missing data, were dropped except when they were conceptually important. RESULTS: The analysis datasets included responses from 9282 patients, 1245 Time 1 caregivers and 1749 Time 2 caregivers. The construct validity of the three proposed outcome composite measures-Overall Quality of Transitional Care (patient and caregiver surveys), Patient Overall Health (patient survey) and Caregiver Effort/Stress (caregiver surveys) -was supported by acceptable exploratory factor analysis results and acceptable internal consistency reliability. Site-level reliability was acceptable for the two patient outcome composite measures, but was low for Caregiver Effort/Stress (< 0.70). In all surveys, the Overall Quality of Transitional Care outcome composite measure was significantly correlated with other outcome composite measures and most of the single-item measures. CONCLUSIONS: Overall, the final patient and caregiver surveys are psychometrically sound and can be used by health systems, hospitals, and researchers to assess the quality of care transitions and related outcomes. Results from these surveys can be used to improve care transitions, focusing on what matters most to patients and their family caregivers.

Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies.

Human cytomegalovirus (HCMV) is an important pathogen in transplant patients and in congenital infection. Previously, we demonstrated that vaccination with a recombinant viral glycoprotein B (gB)/MF59 adjuvant formulation before solid organ transplant reduced viral load parameters post transplant. Reduced posttransplant viremia was directly correlated with antibody titers against gB consistent with a humoral response against gB being important. Here we show that sera from the vaccinated seronegative patients displayed little evidence of a neutralizing antibody response against cell-free HCMV in vitro. Additionally, sera from seronegative vaccine recipients had minimal effect on the replication of a strain of HCMV engineered to be cell-associated in a viral spread assay. Furthermore, although natural infection can induce antibody-dependent cellular cytotoxicity (ADCC) responses, serological analysis of seronegative vaccinees again presented no evidence of a substantial ADCC-promoting antibody response being generated de novo. Finally, analyses for responses against major antigenic domains of gB following vaccination were variable, and their pattern was distinct compared with natural infection. Taken together, these data argue that the protective effect elicited by the gB vaccine is via a mechanism of action in seronegative vaccinees that cannot be explained by neutralization or the induction of ADCC. More generally, these data, which are derived from a human challenge model that demonstrated that the gB vaccine is protective, highlight the need for more sophisticated analyses of new HCMV vaccines over and above the quantification of an ability to induce potent neutralizing antibody responses in vitro.

Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter.

Human cytomegalovirus (HCMV) latency and reactivation rely on a complex interplay between cellular differentiation, cell signaling pathways, and viral gene functions. HCMV reactivation in dendritic cells (DCs) is triggered by IL-6 and extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase signaling. However, activation of the same pathway fails to reactivate HCMV in other myeloid cell types, despite this signaling axis being active in those cells. We hypothesized that IL-6-induced ERK activation initiates the changes in chromatin structure required for viral reactivation but that a concomitant signal is necessary to complete the changes in chromatin structure required for gene expression to occur. Using a differential phosphoproteomics approach in cells that do or do not support IL-6-induced viral reactivation, we identified the concomitant activation of an Src family kinase (SFK), hematopoietic cell kinase (HCK), specifically in DCs in response to IL-6. Pharmacological and genetic inhibition of HCK activity indicated that HCK is required for HCMV reactivation. Furthermore, the HCK/SFK activity was linked to recruitment of the monocytic leukemia zinc finger protein (MOZ) histone acetyltransferase to the viral promoter, which promoted histone acetylation after ERK-mediated histone phosphorylation. Importantly, pharmacological and genetic inhibition of MOZ activity prevented reactivation. These results provide an explanation for the selective activation of viral gene expression in DCs by IL-6, dependent on concomitant SFK and ERK signaling. They also reveal a previously unreported role for SFK activity in the regulation of chromatin structure at promoters in eukaryotic cells via MOZ histone acetyltransferase activity.

A systematic review of the unmet supportive care needs of men on active surveillance for prostate cancer.

OBJECTIVE: Understanding the unmet supportive care needs of men on active surveillance for prostate cancer may enable researchers and health professionals to better support men and prevent discontinuation when there is no evidence of disease progression. This review aimed to identify the specific unmet supportive care needs of men on active surveillance. METHODS: A systematic review following PRISMA guidelines was conducted. Databases (Pubmed, Embase, PsycINFO, and CINAHL) were searched to identify qualitative and/or quantitative studies that reported unmet needs specific to men on active surveillance. Quality appraisals were conducted before results were narratively synthesised. RESULTS: Of the 3613 unique records identified, only eight articles were eligible (five qualitative and three cross-sectional studies). Unmet Informational, Emotional/Psychological, Social, and "Other" needs were identified. Only three studies had a primary aim of investigating unmet supportive care needs. Small active surveillance samples, use of nonvalidated measures, and minimal reporting of author reflexivity in qualitative studies were the main quality issues identified. CONCLUSIONS: The unmet needs of men on active surveillance is an underresearched area. Preliminary evidence suggests the information available and provided to men during active surveillance is perceived as inadequate and inconsistent. Men may also be experiencing unmet psychological/emotional, social, and other needs; however, further representative, high-quality research is required to understand the magnitude of this issue. Reporting results specific to treatment type and utilising relevant theories/models (such as the social ecological model [SEM]) is recommended to ensure factors that may facilitate unmet needs are appropriately considered and reported.

A novel rare sugar inhibitor of murine herpes simplex keratitis.

PURPOSE: To determine the therapeutic efficacy of a novel rare sugar, l-psicose, for the treatment of HSV-1 induced herpetic stromal keratitis (HSK) in a mouse eye model. METHODS: One rare sugar l-psicose was assayed for HSV-1 inhibition of in vitro virus adsorption. The IC50 and IC90 values of l-psicose were determined using plaque reduction assay (PRA) in CV-1 cell. Female Balb/c mice were corneally infected with HSV-1, strain KOS-GFP; A topical eye drop treatment of l-psicose was started 24 h after infection and continued four times daily for ten consecutive days. The severity of HSK was monitored by slit lamp examination in a masked fashion and Infectious HSV-1 shedding was determined by PRA. RESULTS: l-psicose was found to have anti-viral activity in vitro at an IC50 dose of 99.5 mM and an IC90 dose of 160 mM. Topical eye drop treatment with 200 mM l-psicose in PBS solution significantly reduced the severity of HSK compared to the mock treatment group. The in vivo mouse ocular model results of l-psicose therapy correlated with accelerated clearance of virus from eye swabs. CONCLUSION: The results suggest that topical treatment with rare sugar l-psicose has efficacy against HSK through inhibition of HSV-1.

The C5a receptor impairs IL-12-dependent clearance of Porphyromonas gingivalis and is required for induction of periodontal bone loss.

The C5a anaphylatoxin receptor (C5aR; CD88) is activated as part of the complement cascade and exerts important inflammatory, antimicrobial, and regulatory functions, at least in part, via crosstalk with TLRs. However, the periodontal pathogen Porphyromonas gingivalis can control C5aR activation by generating C5a through its own C5 convertase-like enzymatic activity. In this paper, we show that P. gingivalis uses this mechanism to proactively and selectively inhibit TLR2-induced IL-12p70, whereas the same pathogen-instigated C5aR-TLR2 crosstalk upregulates other inflammatory and bone-resorptive cytokines (IL-1ß, IL-6, and TNF-α). In vivo, the ability of P. gingivalis to manipulate TLR2 activation via the C5a-C5aR axis allowed it to escape IL-12p70-dependent immune clearance and to cause inflammatory bone loss in a murine model of experimental periodontitis. In the latter regard, C5aR-deficient or TLR2-deficient mice were both resistant to periodontal bone loss, in stark contrast with wild-type control mice, which is consistent with the interdependent interactions of C5aR and TLR2 in P. gingivalis immune evasion and induction of bone-resorptive cytokines. In conclusion, P. gingivalis targets C5aR to promote its adaptive fitness and cause periodontal disease. Given the current availability of safe and effective C5aR antagonists, pharmacological blockade of C5aR could act therapeutically in human periodontitis and reduce associated systemic risks.

Pathogenic microbes and community service through manipulation of innate immunity.

The periodontal pathogen Porphyromonas gingivalis undermines major components of innate immunity, such as complement, Toll-like receptors (TLR), and their crosstalk pathways. At least in principle, these subversive activities could promote the adaptive fitness of the entire periodontal biofilm community. In this regard, the virulence factors responsible for complement and TLR exploitation (gingipain enzymes, atypical lipopolysaccharide molecules, and fimbriae) are released as components of readily diffusible membrane vesicles, which can thus become available to other biofilm organisms. This review summarizes important immune subversive tactics of P. gingivalis which might enable it to exert a supportive impact on the oral microbial community.

Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay.

OBJECTIVES: To assess whether a commercially available CE-IVD, ELISA-based surrogate neutralisation assay (cPass, Genscript) provides a genuine measure of SARS-CoV-2 neutralisation by human sera, and further to establish whether measuring responses against the RBD of S was a diagnostically useful proxy for responses against the whole S protein. METHODS: Serum samples from 30 patients were assayed for anti-NP responses, for 'neutralisation' by the surrogate neutralisation assay and for neutralisation by SARS-CoV-2 S pseudotyped virus assays utilising two target cell lines. Correlation between assays was measured using linear regression. RESULTS: The responses observed within the surrogate neutralisation assay demonstrated an extremely strong, highly significant positive correlation with those observed in both pseudotyped virus assays. CONCLUSIONS: The tested ELISA-based surrogate assay provides an immunologically useful measure of functional immune responses in a much quicker and highly automatable fashion. It also reinforces that detection of anti-RBD neutralising antibodies alone is a powerful measure of the capacity to neutralise viral infection.

Evaluating the clinical dyad leadership model: a narrative review.

PURPOSE: Dyadic leadership models, in which two professionals jointly lead and share unit responsibilities, exemplifies a recent trend in health care. Nonetheless, much remains unknown about their benefits and drawbacks. In order to understand their potential impact, we conducted a review of literature evaluating dyad leadership models in health systems. DESIGN/METHODOLOGY/APPROACH: Our narrative review began with a search of PubMed, CINAHL, Web of Science and Scopus using key terms related to dyads and leadership. The search yielded 307 articles. We screened titles/abstracts according to these criteria: (1) focus on dyadic leadership model, i.e. physician-nurse or clinician-administrator, (2) set in health care environment and (3) peer-reviewed with an evaluative component of dyadic model. This yielded 22 articles for full evaluation, of which six were relevant for this review. FINDINGS: These six articles contribute an assessment of (1) teamwork and communication perceptions and their changes through dyad implementation, (2) dyad model functionality within the health system, (3) lessons learned from dyad model implementation and (4) dyad model adoption and model fidelity. RESEARCH LIMITATIONS/IMPLICATIONS: Research in this area remains nascent, and most articles focused on implementation over evaluation. It is possible that some articles were excluded due to our methodology, which excluded nonEnglish articles. PRACTICAL IMPLICATIONS: Findings provide guidance for health care organizations seeking to implement dyadic leadership models. Rigorous studies are needed to establish the impact of dyadic leadership models on quality and patient outcomes. ORIGINALITY/VALUE: This review consolidates evidence surrounding the implementation and evaluation of a leadership model gaining prominence in health care.

Assessing Anti-HCMV Cell Mediated Immune Responses in Transplant Recipients and Healthy Controls Using a Novel Functional Assay.

HCMV infection, reinfection or reactivation occurs in 60% of untreated solid organ transplant (SOT) recipients. Current clinical approaches to HCMV management include pre-emptive and prophylactic antiviral treatment strategies. The introduction of immune monitoring to better stratify patients at risk of viraemia and HCMV mediated disease could improve clinical management. Current approaches quantify T cell IFNγ responses specific for predominantly IE and pp65 proteins ex vivo, as a proxy for functional control of HCMV in vivo. However, these approaches have only a limited predictive ability. We measured the IFNγ T cell responses to an expanded panel of overlapping peptide pools specific for immunodominant HCMV proteins IE1/2, pp65, pp71, gB, UL144, and US3 in a cohort of D+R- kidney transplant recipients in a longitudinal analysis. Even with this increased antigen diversity, the results show that while all patients had detectable T cell responses, this did not correlate with control of HCMV replication in some. We wished to develop an assay that could directly measure anti-HCMV cell-mediated immunity. We evaluated three approaches, stimulation of PBMC with (i) whole HCMV lysate or (ii) a defined panel of immunodominant HCMV peptides, or (iii) fully autologous infected cells co-cultured with PBMC or isolated CD8+ T cells or NK cells. Stimulation with HCMV lysate often generated non-specific antiviral responses while stimulation with immunodominant HCMV peptide pools produced responses which were not necessarily antiviral despite strong IFNγ production. We demonstrated that IFNγ was only a minor component of secreted antiviral activity. Finally, we used an antiviral assay system to measure the effect of whole PBMC, and isolated CD8+ T cells and NK cells to control HCMV in infected autologous dermal fibroblasts. The results show that both PBMC and especially CD8+ T cells from HCMV seropositive donors have highly specific antiviral activity against HCMV. In addition, we were able to show that NK cells were also antiviral, but the level of this control was highly variable between donors and not dependant on HCMV seropositivity. Using this approach, we show that non-viraemic D+R+ SOT recipients had significant and specific antiviral activity against HCMV.

Identifying the exercise-based support needs and exercise programme preferences among men with prostate cancer during active surveillance: A qualitative study.

PURPOSE: This study aims to investigate the attitudes and preferences men on active surveillance for prostate cancer have regarding exercise and exercise-based support. Exercise outcomes align with traditionally masculine values, can improve mental and physical health, and may even slow early stage prostate cancer progression. However, attitudes and preferences towards exercise and exercise support are unexplored in men on active surveillance. METHODS: Semi-structured qualitative interviews were conducted with participants (13 males with a history of active surveillance for prostate cancer; 5 female partners). Interviews were conducted either by telephone or in person and audiotaped, transcribed verbatim, and thematically analysed. RESULTS: Several key themes were identified relating to the two research aims: 'Attitudes and Preferences towards Exercise, and 'Attitudes and Preferences towards Exercise Support'. Despite all men engaging in exercise, the majority did not meet the recommended guidelines for cancer survivors. The majority of men either were interested in receiving exercise support or had previously received it, often recommending this for all men on active surveillance. There were varied preferences regarding delivery modality (i.e., online or face to face), the inclusion of partners, and group versus individual formats. CONCLUSIONS: This study provides a novel insight into the attitudes and preferences of men on active surveillance regarding exercise and support. This research will help the development of acceptable and accessible person-centred support for men on active surveillance. However, further research is needed to evaluate the efficacy of different delivery modalities in this population.

A systematic review of the feasibility, acceptability, and efficacy of online supportive care interventions targeting men with a history of prostate cancer.

PURPOSE: To examine the feasibility, acceptability, and efficacy of online supportive care interventions targeting prostate cancer survivors (PCS). METHODS: Studies were identified through structured searches of PubMed, Embase and PsycINFO databases, and bibliographic review. Inclusion criteria were (1) examined feasibility, acceptability, or efficacy of an online intervention designed to improve supportive care outcomes for PCS; (2) presented outcome data collected from PCS separately (if mixed cancer); and (3) evaluated efficacy outcomes using randomized controlled trial (RCT) design. RESULTS: Sixteen studies met inclusion criteria; ten were classified as RCTs. Overall, 2446 men (average age 64 years) were included. Studies reported on the following outcomes: feasibility and acceptability of an online intervention (e.g., patient support, online medical record/follow-ups, or decision aids); reducing decisional conflict/distress; improving cancer-related distress and health-related quality of life; and satisfaction with cancer care. CONCLUSION: We found good preliminary evidence for online supportive care among PCS, but little high level evidence. Generally, the samples were small and unrepresentative. Further, inadequate acceptability measures made it difficult to determine actual PCS acceptability and satisfaction, and lack of control groups precluded strong conclusions regarding efficacy. Translation also appears minimal; few interventions are still publicly available. Larger trials with appropriate control groups and greater emphasis on translation of effective interventions is recommended. IMPLICATIONS FOR CANCER SURVIVORS: Prostate cancer survivors have a variety of unmet supportive care needs. Using online delivery to improve the reach of high-quality supportive care programs could have a positive impact on health-related quality of life among PCS.

Examining the accessibility of high-quality physical activity behaviour change support freely available online for men with prostate cancer.

BACKGROUND: While the internet is considered a promising avenue for providing physical activity support to prostate cancer survivors, little is known about the accessibility of quality websites in the real world. PURPOSE: This work aimed to explore what websites prostate cancer survivors are likely to find when seeking physical activity support online and to evaluate their quality using evidenced-based criteria. METHOD: A search strategy was developed in consultation with prostate cancer survivors (n = 44) to reflect the most common ways they are likely to search the internet. The search was then conducted by a single reviewer, and identified websites were assessed for quality by two reviewers using an evidence-based quality assessment tool developed for this study. Discrepancies were resolved by a third reviewer. RESULTS: Of the 45 identified websites, 13 (29%) received a high quality rating, 22 (49%) received a moderate rating and 10 (22%) received a low quality rating. Higher-quality websites tended to have a .org or .gov domain and tended to be located using searches specific to prostate cancer or prostate cancer and exercise. Very few websites contained complete information regarding the physical activity guidelines for cancer survivors, and no websites provided comprehensive behaviour change support. CONCLUSION: There are some good-quality physical activity websites accessible to men with prostate cancer. However, they may be difficult to find and/or require updating to include complete recommendations and more behaviour change support. IMPLICATIONS FOR CANCER SURVIVORS: Efforts to improve physical activity information online and strategies to direct prostate cancer survivors to higher-quality websites and support services are needed to ensure safety and efficacy.

Human cytomegalovirus and transplantation: drug development and regulatory issues.

Cytomegalovirus (CMV) infection is highly prevalent worldwide and can cause serious disease among immunocompromised individuals, including persons with HIV and transplant recipients on immunosuppressive therapies. It can also result in congenital cytomegalovirus when women are infected during pregnancy. Treatment and prevention of CMV in solid organ and haematopoietic stem cell transplant recipients is accomplished in one of three ways: (1) prophylactic therapy to prevent CMV viraemia; (2) pre-emptive therapy for those with low levels of replicating virus; and (3) treatment for established disease. Despite the high prevalence of CMV, there are few available approved drug therapies, and those that are available are hampered by toxicity and less-than-optimal efficacy. New therapies are being developed and tested; however, inconsistency in standardisation of virus levels and questions about potential endpoints in clinical trials present regulatory hurdles that must be addressed. This review covers the current state of CMV therapy, drugs currently under investigation, and clinical trial issues and questions that are in need of resolution.