Piloting a new cross-sector model of care to support parents with cancer: feasibility and acceptability of the Parent Support Worker role.

PURPOSE: A new Parent Support Worker (PSW) service was piloted in three Australian hospitals. This study assesses the feasibility and acceptability (including preliminary effectiveness) of the service in supporting cancer patients with children. METHODS: A multi-site, mixed-methods study collected quantitative and qualitative data on the effectiveness of the service (pre post-test, n = 36), qualitative and quantitative data on acceptability of the service (survey, n = 43), and qualitative data on acceptability (semi-structured interviews, n = 13). Feasibility was assessed through rates of service uptake amongst referred parents. RESULTS: Of 1133 parents referred, 810 (71%) accepted to receive the service, suggesting high interest in PSW support. Interviewees likewise reported that the service was accessible and facilitated further referrals, indicating good feasibility. Surveys completed three months after accessing PSW support showed high acceptability and satisfaction. Additionally, there was preliminary evidence of service impacts: parents' distress, parenting concerns, parenting efficacy, and stress about situations of concern improved significantly from pre- to post-service (all p < 0.005). Interviewees further described how their emotional coping and confidence to support and communicate with their children had improved through contact with the service. CONCLUSION: The PSW service, integrated into a novel cross-sector model of care, showed to be feasible and acceptable to parent patients and their partners and improved psychological and parenting outcomes. The study suggests refinements to the service and the need for future larger studies to explore the effectiveness of the service in improving parents' outcomes. This study complements previous evidence on the implementation of the PSW service in hospitals.

Cancer awareness in Australian adolescents.

BACKGROUND: Over one-third of cancer cases are attributable to modifiable risk factors. Because health-related behaviors are often established at adolescence, it is important that adolescents understand the risks and lifestyle decisions that may reduce their chances of developing cancer. This study aims to identify the levels of cancer awareness of adolescents in Australia. METHODS: Paper questionnaires were used to collect information about baseline levels of cancer awareness. These questionnaires included socio-demographic questions and the Cancer Awareness Measure (CAM) with slight modifications to ensure their suitability for the Australian adolescent population. Students aged 11 to 19 years were recruited from 13 Australian high schools between 2016 and 2019. RESULTS: A total of 766 adolescents (58% female, mean age = 14.5 years) completed the questionnaires. Adolescents' cancer awareness was low. Adolescents who knew someone with cancer recognized significantly more cancer risk factors and cancer warning signs than those who did not know someone with cancer (t (756) = 2.35, p = .019; t (747) = 5.57, p = .001). Those from high Index of Community Socio-Educational Advantage (ICSEA) schools significantly recognized more cancer risk factors than those from low ICSEA schools (t (764) = 2.42, p = .016). Females recognized significantly more warning signs than males (t (583) = 3.11, p = .002) and students from senior high school grades recognized more warning signs than those from junior grades (t (754) = 2.24, p = .02). Most adolescents (78%) were aware of skin cancer as one of the most common cancers in Australia, however half or less were aware of other common cancers. Although most adolescents would seek medical help in the presence of possible cancer symptoms as soon as possible, approximately 20% of them would not see a doctor promptly. Emotional barriers were the most common reasons to delay seeing a doctor (56%), for example "being worried about hearing bad news" (27%). CONCLUSIONS: Australian adolescents show poor awareness of cancer risk factors and cancer warning signs. A number of demographic and experience factors were found to be related to lower cancer awareness. Education is essential to raise cancer awareness, promote healthy lifestyles from adolescence and avoid a preventable cancer diagnosis.

Cancer patients as parents: implementation of a cross sector service for families with adolescent and young adult children.

BACKGROUND: Cancer patients who are parents show concerns about their ability to parent following diagnosis, and their adolescent and young adult (AYA) children have a need for improved cancer communication within the family. However, psychosocial support for families affected by parental cancer is not routinely available. This study explores the implementation of the Parent Support Worker (PSW) role, as part of a new cross sector model of care to support parent patients, their partners, and AYA children. METHODS: Two PSWs, social workers and healthcare staff (n = 26) from three hospitals participated in audio-recorded, semi-structured interviews about implementation of the PSW role. Template Analysis and Normalization Process Theory were used to analyze the interviews. Data on PSW service activity and referrals of AYA to support from a community organization were analyzed using descriptive statistics. RESULTS: Eleven themes categorized into enablers and barriers of implementation were identified. Regarding acceptability of the role, three enablers (social workers' understanding of the PSW role increasing, easy and prompt access of staff and parent patients to PSWs, satisfaction with the PSW role) and one barrier (communication related confusion and frustration about the PSW role) were identified. Additionally, three enablers (the PSW role fills gaps in parenting-focused support and continuity of care, the PSW role alleviates social workers' workload, negotiation helped to define responsibilities) and one barrier (fear of social work roles to be overtaken by PSWs) for appropriateness of the role were found. Finally, two enablers of feasibility of the role (PSWs and social workers co-managing the work, higher confidence from hospital staff to talk about children in the family) and one barrier (lack of systematic identification and referral processes) were identified. Across hospitals, the number of referrals of AYA children to the community organization increased between 2.7 and 12 times nine months post-introduction of the service. CONCLUSIONS: Established in response to identified gaps in oncology care for parents with cancer, their partners and AYA children, a novel cross-sector model of care was acceptable, appropriate, and feasible. Barriers and enablers to implementation identified in this study need to be considered when designing and implementing similar services.

Standardized videos in addition to the surgical curriculum in Medical Education for surgical clerkships: a cohort study.

BACKGROUND: Medical students are expected to translate the theoretical knowledge gained during their study to practical knowledge during the clerkships. A surgical educational platform with standardized videos may be the solution. However, the effects of a structured online video-based platform in addition to the standard curriculum on students' self-reported and tested surgical knowledge during the surgical clerkship must be assessed. METHODS: Fourth-year medical students (n = 178) participated in a 6-week course of theoretical and practical training followed by a 10-week in-hospital clerkship in the Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands and 11 affiliated general hospitals. Ninety students followed the usual surgical curriculum (control group), followed by 88 students who were given voluntary access to a video-based surgical educational platform of Incision Academy (video group). At the start (T0) and end (T1) of the clerkship, both groups filled out a surgical knowledge test and a survey regarding their self-reported surgical knowledge and their access to available study sources. Supervisors were blinded and surveyed concerning students' performance and their acquired knowledge. We analyzed the data using paired and unpaired student t-tests and linear regression. RESULTS: At the end of the clerkship, students in the video group indicated that they had better resources at their disposal than the control group for surgical procedures (p = 0.001). Furthermore, students in the video group showed a greater increase in self-reported surgical knowledge during their clerkship (p = 0.03) and in more objectively tested surgical knowledge (p < 0.001). CONCLUSIONS: An online surgical educational platform with standardized videos is a valuable addition to the current surgical curriculum according to students and their supervisors. It improves their test scores and self-reported surgical knowledge. Students feel better prepared and more able to find the information necessary to complete the clerkship. TRIAL REGISTRATION: Registry not necessary according to ICMJE guidelines.

National study of newborn hearing screening: programme sensitivity and characteristics of undetected children.

UNLABELLED: The success of universal newborn hearing screening (UNHS) programmes is usually evaluated by determining the effect of the early detection of hearing loss on developmental outcome. However, in practice, these programmes do not detect all children with permanent childhood hearing impairment. In this study we determine the sensitivity of the current UNHS programme and analyse the characteristics of the children not detected by UNHS. We performed a nationwide, population-based, retrospective follow-up study in The Netherlands. All children born in 2003-05 and screened in a hearing screening programme (well babies and neonatal intensive care (NICU) graduates) were included for study. The main outcome measure was the sensitivity of the UNHS programme (based on the proportion of children known to have a permanent childhood hearing impairment in 2008 who were identified by UNHS). We also evaluated age at diagnosis, severity, and aetiology of hearing impairment in the children not detected by UNHS. We found that the sensitivity of the current UNHS programme was 0.83 (0.79 for well babies and 0.96 for NICU graduates). Permanent childhood hearing impairment was confirmed before 36 months of age in 96% of the study cohort. Of the children unidentified by the UNHS, > 50% had moderate hearing loss. No predominant cause of hearing impairment was found in these children. CONCLUSION: Our current UNHS programme identified the majority of children with a permanent hearing impairment of congenital cause.

Magnetic domain fluctuations in an antiferromagnetic film observed with coherent resonant soft x-ray scattering.

We report the direct observation of slow fluctuations of helical antiferromagnetic domains in an ultrathin holmium film using coherent resonant magnetic x-ray scattering. We observe a gradual increase of the fluctuations in the speckle pattern with increasing temperature, while at the same time a static contribution to the speckle pattern remains. This finding indicates that domain-wall fluctuations occur over a large range of time scales. We ascribe this nonergodic behavior to the strong dependence of the fluctuation rate on the local thickness of the film.

Analysis of aqueous humor immunoglobulin G in uveitis by enzyme-linked immunosorbent assay, isoelectric focusing, and immunoblotting.

Immunoglobulin G (IgG) in aqueous humor from patients with various uveitis syndromes was analyzed using a number of immunologic techniques. Sixty-five percent of patients with Fuchs' heterochromic cyclitis (FHC), 70% of patients with other forms of uveitis, and 44% of controls showed local synthesis of IgG, as demonstrated by an elevated IgG:albumin relative concentration ratio. Using an enzyme-linked immunosorbent assay to measure the concentration of IgG subclasses 1-4, a relative excess of IgG1 was found in the aqueous compared with the serum in FHC. Isoelectric focusing and immunoblotting studies revealed oligoclonal IgG bands in the aqueous of 13 of 23 (57%) patients with FHC, most being of the IgG1 subclass. Oligoclonal bands were not found in 18 patients with other types of uveitis or 13 patients undergoing surgery for senile cataract. These findings indicate intraocular production of IgG of restricted specificity in FHC, providing further evidence for local immune dysfunction in this condition. As yet the antigenic stimulus for this oligoclonal B-cell response has not been identified.

51Cr release assay of clozapine-induced cytotoxicity: evidence for immunogenic mechanism.

Serum drawn from patients during clozapine-induced agranulocytosis was toxic to human polymorphonuclear leukocytes (PMNs). Toxicity was produced by an immunoglobulin fraction, predominantly of the IgM class. The offending drug was not necessary at this stage to produce cytotoxicity. These effects were observed by inhibiting post-phagocytosis glycolysis, by ejection of trypan blue, or by enhanced release of 51Cr from lysed-labeled PMNs. Direct chemical toxicity, produced by clozapine or its metabolites, was tested by similar procedures. At a concentration of 10(-5) M in a colloidal milieu produced by dilution with AB serum, no cytotoxicity was observed; however, in aqueous medium. N-desmethylclozapine was toxic to PMNs and proliferating lymphocytes. Post-recovery serum appeared to be inert, but cytotoxicity was restored by adding clozapine or N-desmethylclozapine to the sensitive patient's serum. At this stage, cytotoxicity as measured by 51Cr release was abrogated by anti-IgG or anti-IgM. These relationships favor an immunologic mechanism that damages peripheral PMNs. Development of colony-forming units-granulocyte (CFU-G) was similarly inhibited in normal marrow cultures by cytotoxic serum alone, whereas no metabolite had such an effect at the same concentration (10(-5) M).

On the possible mechanisms and predictability of clozapine-induced agranulocytosis.

Studies were conducted on serum removed from 15 patients before, during, and after, clozapine-induced agranulocytosis. Cytotoxic studies were compared with samples taken from patients during treatment with clozapine who did not develop agranulocytosis or treatment controls (TC); additional controls consisted of allogeneic (NC) and autogeneic serum from apparently normal people. The effect of serum on measurable functions of polymorphonuclear neutrophils (PMNs) taken from normal people was tested. Procedures under study included suppression of post-phagocytosis-induced 14CO2-indicated respiratory burst, as well as ejection of trypan blue by test PMNs. PMNs exposed to active agranulocytosis serum plus complement displayed diminished 14CO2 emission during phagocytosis or failed to eject trypan blue. PMNs exposed to serum of TC and NC continued to function normally as regards 14CO2 emission and trypan blue ejection. Five patients studied before the development of agranulocytosis showed suppressed PMN function, which increased to peak value during agranulocytosis and then disappeared within 40 days of recovery. Similar suppression of colony forming units of granulocytes and macrophages (CFU-GM) was found whenever agranulocytosis serum was included in the marrow culture. The cytotoxic material required complement for its full expression, was not dialysable, was neutralised by anti-IgM serum, and was absorbed by test PMNs. Furthermore, solutions of clozapine or 5 of its metabolites offered no similar suppression of PMN function in vitro after incubation in an aqueous medium or with normal serum. These observations favour development of an immunogenic clone in sensitive people during active treatment with clozapine, which eventually leads to precipitous depletion of PMNs and their precursors. The early appearance of this suppressive substance may offer an early warning for development of agranulocytosis.

Human Papillomavirus and Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study regarding Tobacco and Alcohol Consumption.

We aimed to determine the role of HPV in the pathogenesis and outcome of oropharyngeal squamous cell carcinoma (OSCC) in lifelong nonsmoking and nondrinking patients. A case-case analysis was performed to compare the presence of HPV-DNA in tumor cells of 16 nonsmoking and nondrinking with 16 matched smoking and drinking patients (matching criteria: age at incidence, gender, tumor sublocation, tumor stage). HPV was detected using 2 PCR tests, FISH analysis, and p16(INK4A) immunostaining. Nonsmoking and nondrinking patients had more HPV-positive tumors than smoking and drinking patients (n = 12; 75% versus n = 2; 13%; P < 0.001). All HPV-positive tumors showed p16(INK4A) overexpression, and 1 HPV-negative tumor had p16(INK4A) overexpression, (P < 0.001). Overall survival and disease-specific survival were higher for HPV-positive compared to HPV-negative cases (P = 0.027, P = 0.039, resp.). In conclusion, HPV is strongly associated with OSCC of nonsmoking and nondrinking patients. Specific diagnostic and therapeutic actions should be considered for these patients to achieve a better prognosis.

DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands.

BACKGROUND: A significant number of asymptomatic newborns infected with congenital cytomegalovirus (CMV) will present with permanent childhood hearing impairment (PCHI) during early childhood. OBJECTIVES: To investigate the role of congenital CMV infection in causing PCHI in the Netherlands, and assess the efficacy of two different hearing screening strategies and the developmental outcome following each strategy. STUDY DESIGN: We included 192 children with PCHI at the age of 3-5 years, who were offered hearing screening in their first year of life. Dried blood spots from 171 children were available for CMV detection using real-time PCR. The results of eight previously tested samples were also available. Clinical baseline characteristics were collected from medical records and the Child Development Inventory was used to investigate the developmental outcome. RESULTS: The rate of congenital CMV among the 179 children was 8% (14/179) and 23% (9/39) among children with profound PCHI. Two of eight CMV-positive children with PCHI at the age of 3-5 years had passed the newborn hearing screening (NHS) test. Developmental outcome measures showed a significantly greater delay in language comprehension in children with both PCHI and congenital CMV infection (the largest in symptomatic children) than in the children with PCHI without congenital CMV infection. CONCLUSIONS: Congenital CMV infection is important in the etiology of PCHI. Universal NHS is not a guarantee of normal hearing and development in childhood for children with congenital CMV infection. This is a problem which might be solved by universal congenital CMV screening.

Generation of Aspergillus- and CMV- specific T-cell responses using autologous fast DC.

BACKGROUND: Recent reports have described a new strategy for differentiation and maturation of monocyte (Mo)-derived DCs within only 48 h of in vitro culture (fast-DC). Here we assess the efficacy of the fast-DC to process and present different Aspergillus fumigatus and CMV Ag preparations to autologous T cells, compared with DCs generated in standard 7-day cultures (standard-DC). METHODS: Adherent blood Mo were treated with GM-CSF and IL-4 (1 day for fast-DC, 5 days in the standard-DC) to generate immature DCs, and then were matured for either 1-2 days (fast-DC) or 2 days (standard-DC) with inflammatory cytokines. DCs were pulsed with A. fumigatus or CMV Ag preparation immediately prior to maturation, or infected after maturation with adeno-pp65. Mature DCs were then used to prime Ag-specific proliferative and cytotoxic T lymphocytes (CTL) responses. RESULTS: Fast-DC were CD14- and expressed mature DC surface markers to the same degree as standard-DC, and maintained this phenotype after withdrawing cytokine from the cultures. Fast-DC and standard-DC were equally capable of inducing A. fumigatus and CMV-specific T-cell proliferation, as well as priming Ag-specific CTL activity. The Aspergillus- and CMV-specific CTL were of mixed CD3+/CD4+ and CD3+/CD8+ phenotype, and specifically killed autologous DC pulsed with A. fumigatus Ag and autologous CMV infected fibroblasts, respectively. DISCUSSION: Fast-DC are as effective as standard-DC in the generation of Ag-specific T-cell responses. Moreover, use of fast-DC not only reduces labor and supply cost, as well as workload and time, but also increases the number of DCs derived from adherent Mo, which may facilitate the use of DCs in clinical trials of cellular immunotherapy.

Suppression of EBV release from irradiated B lymphoblastoid cell-lines: superior activity of ganciclovir compared with acyclovir.

BACKGROUND: B lymphoblastoid cell-lines (BLCL), generated by exposure of PBMC to a laboratory strain of EBV, are commonly utilized in the preparation of T cells used for immunotherapy. Although most B cells are latently infected, BLCL contain a subset of cells that harbor infectious virus, which could be released into the infusion product during preparation. To reduce this known risk, laboratories have pretreated BLCL for > or = 14 days with 100 microM acyclovir (ACV), an inhibitor of viral DNA polymerase, prior to use. We tested the effectiveness of ACV in preventing the release of infectious virus from irradiated fresh and previously frozen BLCL, and compared its effects with those of ganciclovir (GCV). METHODS: BLCL were grown for 14 days in medium containing various doses of ACV or GCV, washed, irradiated, and tested for the presence of infectious virus in co-culture assays with cord blood mononuclear cells(CBMC) (21 CBMC to BLCL). B-cell transformation was assessed at 3-4 weeks of culture. RESULTS: Both fresh and previously frozen BLCL released infectious virus, which transformed nearly all (92%) of CBMC co-cultures (n = 52). Transformation was not prevented by treatment with 100 microM ACV (88%, n = 52). Increasing the ACV dose to 200 microM (or 50 microg/mL) still allowed transformation in 4/9 (44%) cultures, while this and higher doses severely reduced the proliferation rate of the BLCL during ACV exposure. Infectious virus release was detectable within 1 day of ACV removal and BLCL irradiation. In contrast, GCV was able to prevent infectious virus release in 12/12 co-cultures at a concentration (15 microM) that only modestly reduced BLCL growth. DISCUSSION: These results indicate that GCV is more effective at preventing release of infectious EBV from irradiated BLCL than ACV at concentrations that do not severely inhibit B-cell growth.

Cytotoxic activity in serum of patients with clozapine-induced agranulocytosis.

Studies were conducted on serum samples collected from 15 patients during the course of clozapine-induced agranulocytosis. During acute phases of agranulocytosis, serum was cytotoxic to peripheral polymorphonuclear neutrophils (PMNs), as indicated by complement-dependent suppression of postphagocytosis respiratory burst and by increased retention of trypan blue dye by test PMNs. Cytotoxicity was removed by adsorption with allogeneic PMNs, was attenuated by antibody to immunoglobulin M but not by antibody to immunoglobulin G antigen-binding fragment, was not dialyzable, and was partially removed by 2-mercaptoethanol and dialysis. Three patients in a longitudinal study all had perturbed postphagocytosis respiratory burst 20 days before agranulocytosis developed. In all patients cytotoxicity disappeared less than 40 days after treatment when the offending drug was discontinued. Trypan blue dye reactivity was similar when tested. At 20% of culture medium, all serum samples partially suppressed development of colony-forming units of granulocytes and macrophages (CFU-GM) in marrow cultures. At 40% of culture medium, agranulocytosis serum suppressed CFU-GM completely but did not inhibit development of colony-forming units of erythroblasts (CFU-E) or burst-forming units of erythroblasts (BFU-E). Addition of clozapine alone or to agranulocytosis serum neither enhanced nor suppressed toxicity to peripheral PMNs. Neither clozapine nor its toxic metabolic end-products directly produced equivalent cytotoxicity to cellular function or proliferation at 10(-5)mol/L. Serum from patients given clozapine who did not have agranulocytosis and samples from allogeneic normal subjects were not cytotoxic to test PMNs. Cytotoxicity was specific to granulocyte cell lines because development of CFU-GM was inhibited by agranulocytosis serum, whereas CFU-E and BFU-E were not similarly affected. Further studies are in progress to distinguish between immunogenic and non-immunogenic mechanisms.

Cytomegalovirus-specific cytolytic T-cell lines and clones generated against adenovirus-pp65-infected dendritic cells.

Cytomegalovirus (CMV) infection is a serious complication of allogeneic bone marrow transplantation (BMT). CMV disease can usually be prevented by passive immunization with donor-derived CMV-pp65-specific T-cell clones if provided early post-BMT. The classic method of generating CMV-specific T-cell clones requires donor-derived fibroblast lines infected with CMV as stimulators, thus limiting the availability of CMV immunotherapy to those patients for whom a donor skin biopsy can be obtained 6 to 8 weeks pretransplantation. To overcome this limitation we have used monocyte-derived dendritic cells (DCs) to induce donor anti-CMV cytotoxic T lymphocytes (CTLs). Matured, adeno-pp65-infected DCs were added at day 0 and at day 7 of a 2-week culture of donor peripheral blood mononuclear cells. DC-primed cultures were compared with cultures stimulated in an identical fashion with CMV-infected fibroblasts or with adeno-pp65-infected freshly isolated blood monocytes. Specific killing of CMV-infected fibroblasts was detected in all except the culture stimulated with pp65-infected monocytes. DCs infected after maturation elicited greater CTL activity than did DCs matured after infection. A series of 5 CD8+ clones from a fibroblast-stimulated culture and 7 CD8+ clones from a mature-DC-stimulated culture derived from a single HLA-A*0201+ individual were characterized. All 12 clones lysed autologous CMV-infected fibroblasts. All except 1 clone from the CMV-infected fibroblast arm (fibroblast arm) lysed vaccinia-pp65-infected B-lymphoblastoid cell lines (BLCLs); none lysed vaccinia-pp150-infected or noninfected BLCLs. Ten of 10 CD8+ clones tested were restricted by HLA-A*0201. Seven of the 12 clones were Vbeta6+ (2 from the fibroblast arm and 5 from the DC arm) with an identical Vbeta6.1-J1.4 sequence. Three clones from the fibroblast arm and 5 clones from the DC arm recognized the pp65 peptide NLVPMVATV (amino acids [aa], 495-503). These data show that CMV-specific T-cell clones with similar restriction patterns, T cell-receptor usage, and specificity can be generated using monocyte-derived pp65-infected-DC or CMV-infected-fibroblast stimulators. This approach should broaden the applicability of CMV-specific T-cell immunotherapy to a wider spectrum of patients by reducing the time required to generate CMV-specific T-cell clones.