Coping Strategies of Patients With Advanced Lung or Colorectal Cancer Over Time: Insights From the International ACTION Study.

OBJECTIVE: A comprehensive understanding of coping strategies of patients with advanced diseases can contribute to providing supportive care that meets patients' needs. However, insight into how coping of this population develops over time is lacking. We examined coping strategies of patients with advanced cancer over time and identified distinct trajectories and their predictors. METHODS: Data from 675 patients of the control group from the ACTION cluster-randomized trial were analyzed. Patients with lung or colorectal cancer from six European countries (Belgium, Denmark, Italy, the Netherlands, Slovenia and the United Kingdom) completed questionnaires at baseline, 12 and 20 weeks. Measures included Denial, Acceptance, and Problem-focused coping (COPE, Brief COPE inventory; scores 4-16 per scale). We used linear mixed models to analyze the data and latent class mixed models to identify stable (within patient change < 2) coping strategies. RESULTS: At baseline, patients reported low use of Denial (6.6) and greater use of Acceptance (12.6) and Problem-Focused coping (12.2). These scores did not significantly change. We found four distinct trajectories for the use of Denial, three for Acceptance and five for Problem-Focused coping strategies. Stable trajectories were found in 513 (77%) patients for Denial, 645 (96%) for Acceptance and 602 (91%) for Problem-Focused coping. All coping strategies were stable in 447 (68%) patients and two were stable in 181 patients (28%). CONCLUSIONS: Overall, the use of coping strategies was rather stable in the majority of patients with advanced cancer. However, for each of the coping strategies subgroups of patients reported fluctuating coping trajectories.

Vaccines for COVID-19.

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled-up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases.

Compromised CD4:CD8 ratio recovery in people living with HIV aged over 50 years: an observational study.

OBJECTIVES: Persistent CD4:CD8 ratio inversion (< 1) is associated with mortality in older people. We investigated the interaction of the effects of baseline CD8 count and age at HIV diagnosis on CD4:CD8 ratio recovery with antiretroviral therapy (ART). METHODS: An observational study (1 January 2007 to 31 December 2016) was carried out using routinely collected data from the HIV outpatient services at Imperial College Healthcare NHS Trust, London, UK. CD4 and CD8 counts, prior to and during ART, treatment during primary HIV infection (PHI) and HIV-1 viral load were included in univariate and multivariate analyses using Cox proportional hazard regression. RESULTS: Data were included for 876 patients starting ART, where HIV suppression was achieved. Of these patients, 741 of 876 (84.6%) were male and 507 of 876 (57.9%) were Caucasian. The median time on ART was 38 [interquartile range (IQR) 17-66] months. CD8 count change on ART was bidirectional; low CD8 counts (≤ 600 cells/µL) increased and high CD8 counts (> 900 cells/µL) decreased. The median pre-ART CD4:CD8 ratio was 0.41 (IQR 0.24-0.63), and recovery (≥ 1) occurred in 274 of 876 patients (31.3%). Pre- and post-ART CD4:CD8 ratios were lower in those aged > 50 years compared with young adults aged 18-30 years (P < 0.001 and P = 0.002, respectively). After adjustment, younger age at HIV diagnosis (P < 0.001) and treatment during PHI (P < 0.001) were favourable for CD4:CD8 ratio normalization. CONCLUSIONS: Older age (> 50 years) at HIV diagnosis was associated with persistent CD4:CD8 ratio inversion, whereas treatment of PHI was protective. These findings confirm the need for testing and early treatment of people aged > 50 years, and could be used in a risk management algorithm for enhanced surveillance.

Anti-Müllerian hormone in managed African and Asian rhino species.

Serum collected across the lifespan of four managed rhino species: black (Diceros bicornis, n = 16), white (Ceratotherium simum simum, n = 19), greater one-horned (GOH, Rhinoceros unicornis, n = 11) and Sumatran (Dicerorhinus sumatrensis, n = 6) were validated and analyzed in an anti-Müllerian hormone (AMH) enzyme- linked immunoassay. Concentrations of AMH were examined over time, between sexes and throughout different reproductive states which included n = 3 female white rhinos immunocontracepted with porcine zona pellucida (pZP). Across species, males produced higher AMH concentrations compared to females. Among males, AMH concentrations varied by species aside from comparable values secreted between black and white rhinos. The GOH and Sumatran rhino secreted the highest and lowest male AMH concentrations, respectively. However, within each species, AMH concentrations were similar across male age categories. Preliminary insight into male AMH changes from birth to sexual maturity suggest its potential as a marker for onset of testicular maturation. Female black, GOH and Sumatran rhinos secreted comparable AMH concentrations which were higher than those in white rhino. Within each species, inter-individual variation in AMH secretion occurred among females of similar age. While AMH secretion did not differ across the ages sampled for female white (4->26 yr) and GOH (4-26 yr) rhinos, black and Sumatran rhinos >26 and <4 yr, respectively secreted lower AMH compared to conspecific females 7-26 yr of age. Two idiopathic infertility cases corresponded to low (outside species range) AMH values. The establishment of normative AMH concentrations in managed African and Asian rhinos provides an additional metric beyond traditional sex steroids to assess gonadal function. Further work is needed to determine if AMH can predict fertility potential in rhinos.

Impact of an influenza information pamphlet on vaccination uptake among Polish pupils in Edinburgh, Scotland and the role of social media in parental decision making.

BACKGROUND: In Edinburgh, Scotland, lower influenza vaccine uptake has been observed in primary school children in the Polish community. METHODS: To address this disparity, the Polish-language version of the NHS Health Scotland influenza information pamphlet was updated and distributed in 2018 to all identified Polish pupils attending three pilot schools. The impact of the revised pamphlet was evaluated by examining changes in vaccine uptake in these schools as compared to a control group of schools, and a questionnaire was issued to all Polish parents in the pilot schools to explore their opinions of the pamphlet and preferred sources of immunisation information. RESULTS: On average uptake was 7.4% (95% CI 1.0-13.8%, p < 0.05) higher in the three pilot schools in which the Polish-language pamphlet was distributed (28.7%) than control schools (21.3%). The questionnaire feedback was that 37.3% of respondents felt better-informed about the influenza vaccine following the pamphlet. The respondents reported that the most important information source in deciding whether to vaccinate is previous experience. Healthcare professionals were ranked lower in importance when making a decision. Parents, who refused consent (n = 65) were more likely to source information from social media, friends and family, and Polish websites compared with those who consented (n = 45). CONCLUSIONS: These findings suggest that issuing new Polish health literature was associated with a large increase in consent form return rate and a modest increase in uptake of the influenza vaccine by Polish pupils in the pilot schools. Social media and Polish websites were found to have a greater influence over Polish parents' decision to immunise than UK healthcare staff and health authority information. Intensive effort is required to encourage parents towards information sources where more accurate pro-vaccination messages can be promulgated by national health services and independent expert groups. The role of social media for migrant communities requires careful consideration, especially for vaccine programmes not delivered in their country of birth.

Trained facilitators' experiences with structured advance care planning conversations in oncology: an international focus group study within the ACTION trial.

BACKGROUND: In oncology, Health Care Professionals often experience conducting Advance Care Planning (ACP) conversations as difficult and are hesitant to start them. A structured approach could help to overcome this. In the ACTION trial, a Phase III multi-center cluster-randomized clinical trial in six European countries (Belgium, Denmark, Italy, the Netherlands, Slovenia, United Kingdom), patients with advanced lung or colorectal cancer are invited to have one or two structured ACP conversations with a trained facilitator. It is unclear how trained facilitators experience conducting structured ACP conversations. This study aims to understand how facilitators experience delivering the ACTION Respecting Choices (RC) ACP conversation. METHODS: A qualitative study involving focus groups with RC facilitators. Focus group interviews were recorded, transcribed, anonymized, translated into English, and thematically analysed, supported by NVivo 11. The international research team was involved in data analysis from initial coding and discussion towards final themes. RESULTS: Seven focus groups were conducted, involving 28 of in total 39 trained facilitators, with different professional backgrounds from all participating countries. Alongside some cultural differences, six themes were identified. These reflect that most facilitators welcomed the opportunity to participate in the ACTION trial, seeing it as a means of learning new skills in an important area. The RC script was seen as supportive to ask questions, including those perceived as difficult to ask, but was also experienced as a barrier to a spontaneous conversation. Facilitators noticed that most patients were positive about their ACTION RC ACP conversation, which had prompted them to become aware of their wishes and to share these with others. The facilitators observed that it took patients substantial effort to have these conversations. In response, facilitators took responsibility for enabling patients to experience a conversation from which they could benefit. Facilitators emphasized the need for training, support and advanced communication skills to be able to work with the script. CONCLUSIONS: Facilitators experienced benefits and challenges in conducting scripted ACP conversations. They mentioned the importance of being skilled and experienced in carrying out ACP conversations in order to be able to explore the patients' preferences while staying attuned to patients' needs. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry 63110516 ( ISRCTN63110516 ) per 10/3/2014.

CD4:CD8 ratio in children with perinatally acquired HIV-1 infection.

OBJECTIVES: In adults with horizontally acquired HIV infection, an inverted CD4:CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non-AIDS-defining adverse events. Normalization of this ratio with antiretroviral therapy (ART) is suboptimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4:CD8 ratio recovery in children with perinatally acquired HIV infection (PaHIV) on ART. METHODS: A cross-sectional, retrospective analysis of routine clinical data in children with PaHIV (5-18 years old) attending a single UK centre was carried out. RESULTS: CD4:CD8 normalization was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4:CD8 ratio and age at start of ART. Positive correlations were found between current CD4:CD8 ratio and total time with suppressed HIV viral load and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4:CD8 ratio (standardized ß = -0.680; P < 0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery. CONCLUSIONS: We found higher rates of CD4:CD8 ratio normalization compared with previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV-positive adults and children will enhance immunological normalization.

Advance care planning: A systematic review about experiences of patients with a life-threatening or life-limiting illness.

BACKGROUND: Advance care planning is seen as an important strategy to improve end-of-life communication and the quality of life of patients and their relatives. However, the frequency of advance care planning conversations in practice remains low. In-depth understanding of patients' experiences with advance care planning might provide clues to optimise its value to patients and improve implementation. AIM: To synthesise and describe the research findings on the experiences with advance care planning of patients with a life-threatening or life-limiting illness. DESIGN: A systematic literature review, using an iterative search strategy. A thematic synthesis was conducted and was supported by NVivo 11. DATA SOURCES: The search was performed in MEDLINE, Embase, PsycINFO and CINAHL on 7 November 2016. RESULTS: Of the 3555 articles found, 20 were included. We identified three themes in patients' experiences with advance care planning. 'Ambivalence' refers to patients simultaneously experiencing benefits from advance care planning as well as unpleasant feelings. 'Readiness' for advance care planning is a necessary prerequisite for taking up its benefits but can also be promoted by the process of advance care planning itself. 'Openness' refers to patients' need to feel comfortable in being open about their preferences for future care towards relevant others. CONCLUSION: Although participation in advance care planning can be accompanied by unpleasant feelings, many patients reported benefits of advance care planning as well. This suggests a need for advance care planning to be personalised in a form which is both feasible and relevant at moments suitable for the individual patient.

An audit of Cryptosporidium and Giardia detection in Scottish National Health Service Diagnostic Microbiology Laboratories.

Giardia duodenalis and Cryptosporidium species are protozoan parasites capable of causing gastrointestinal disease in humans and animals through the ingestion of infective faeces. Whereas Cryptosporidium species can be acquired locally or through foreign travel, there is the mis-conception that giardiasis is considered to be largely travel-associated, which results in differences in laboratory testing algorithms. In order to determine the level of variation in testing criteria and detection methods between diagnostic laboratories for both pathogens across Scotland, an audit was performed. Twenty Scottish diagnostic microbiology laboratories were invited to participate with questions on sample acceptance criteria, testing methods, testing rates and future plans for pathogen detection. Reponses were received from 19 of the 20 laboratories representing each of the 14 territorial Health Boards. Detection methods varied between laboratories with the majority performing microscopy, one using a lateral flow immunochromatographic antigen assay, another using a manually washed plate-based enzyme immunoassay (EIA) and one laboratory trialling a plate-based EIA automated with an EIA plate washer. Whereas all laboratories except one screened every stool for Cryptosporidium species, an important finding was that significant variation in the testing algorithm for detecting Giardia was noted with only four laboratories testing all diagnostic stools. The most common criteria were 'travel history' (11 laboratories) and/or 'when requested' (14 laboratories). Despite only a small proportion of stools being examined in 15 laboratories for Giardia (2%-18% of the total number of stools submitted), of interest is the finding that a higher positivity rate was observed for Giardia than Cryptosporidium in 10 of these 15 laboratories. These findings highlight that the underreporting of Giardia in Scotland is likely based on current selection and testing algorithms.

An outbreak of mumps with genetic strain variation in a highly vaccinated student population in Scotland.

An outbreak of mumps within a student population in Scotland was investigated to assess the effect of previous vaccination on infection and clinical presentation, and any genotypic variation. Of the 341 cases, 79% were aged 18-24. Vaccination status was available for 278 cases of whom 84% had received at least one dose of mumps containing vaccine and 62% had received two. The complication rate was 5·3% (mainly orchitis), and 1·2% were admitted to hospital. Genetic sequencing of mumps virus isolated from cases across Scotland classified 97% of the samples as genotype G. Two distinct clusters of genotype G were identified, one circulating before the outbreak and the other thereafter, suggesting the virus that caused this outbreak was genetically different from the previously circulating virus. Whilst the poor vaccine effectiveness we found may be due to waning immunity over time, a contributing factor may be that the current mumps vaccine is less effective against some genotypes. Although the general benefits of the measles-mumps-rubella (MMR) vaccine should continue to be promoted, there may be value in reassessing the UK vaccination schedule and the current mumps component of the MMR vaccine.

Reduction in colposcopy workload and associated clinical activity following human papillomavirus (HPV) catch-up vaccination programme in Scotland: an ecological study.

OBJECTIVE: To measure patterns of clinical activity at colposcopy before and after vaccinated women entered the Scottish Cervical Screening Programme (SCSP). DESIGN: Population-based observational study using nationally collected data. SETTING: Scottish colposcopy clinics. SAMPLE: All women with a date of birth on or after 1 January 1985 who attended colposcopy in Scotland between 2008 and 2014. METHODS: Routinely collected data from the Scottish National Colposcopy Clinical Information Audit System (NCCIAS) were extracted, including: referral criteria, referral cervical cytology, colposcopic findings, clinical procedures, and histology results. Analysis was restricted to those referred to colposcopy at age 20 or 21 years. MAIN OUTCOME MEASURES: Referral criteria, positive predictive value of colposcopy, default rates, and rates of cervical biopsies and treatments. RESULTS: A total of 7372 women referred for colposcopy at age 20 or 21 years were identified. There was a downward trend in the proportion of those referred with abnormal cytology (2008/9, 91.0%; 2013/14, 90.3%; linear trend P = 0.03). Women were less likely to have diagnostic or therapeutic interventions. The proportion with no biopsy (2008/9, 19.5%; 2013/14, 26.9%; linear trend P < 0.0001) and no treatment (2008/9, 74.9%; 2013/14, 91.8%; linear trend P < 0.0001) increased over the period of observation. CONCLUSIONS: A reduction in clinical activity related to abnormal screening referrals is likely to be associated with the human papillomavirus (HPV) catch-up immunisation programme. Referral criteria and the service provision of colposcopy needs to be planned carefully, taking account of the increasing number of women who have been immunised against HPV that will be entering cervical screening programmes worldwide. TWEETABLE ABSTRACT: Colposcopy referral criteria and service planning need attention following HPV immunisation programme.

The impact of human papillomavirus type on colposcopy performance in women offered HPV immunisation in a catch-up vaccine programme: a two-centre observational study.

OBJECTIVE: To determine whether human papillomavirus (HPV) immunisation has affected the prevalence of HPV genotypes and colposcopic features of cervical intraepithelial neoplasia (CIN) in young women referred for colposcopy. DESIGN: A two-centre observational study including vaccinated and unvaccinated women. SETTING: Colposcopy clinics serving two health regions in Scotland, UK. POPULATION: A total of 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening. METHODS: Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16, 18, 31, 33, and 45. Demographic data, cytology, and histology results and colposcopic features were recorded. Chi-square analysis was conducted to identify associations between vaccine status, HPV genotypes, and colposcopic features. MAIN OUTCOME MEASURES: Colposcopic features, HPV genotypes, mRNA expression, and cervical histology. RESULTS: The prevalence of HPV 16 was significantly lower in the vaccinated group (8.6%) compared with the unvaccinated group (46.7%) (P = 0.001). The number of cases of CIN2+ was significantly lower in women who had been vaccinated (P = 0.006). The HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features, but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+, from 74% (unvaccinated) to 66.7% (vaccinated). CONCLUSIONS: In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch-up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in women who have been vaccinated is at the lower acceptable level of the UK national cervical screening programme guidelines. TWEETABLE ABSTRACT: Reduction of hrHPV positivity and CIN in immunised women consistent with lower PPV of colposcopy for CIN2+.

Posttraumatic stress following spinal cord injury: a systematic review of risk and vulnerability factors.

OBJECTIVES: To summarise quantitatively the available evidence relating to pretraumatic, peritraumatic and posttraumatic characteristics that may increase or decrease the risk of developing posttraumatic stress disorder (PTSD) following spinal cord injury (SCI). STUDY DESIGN: Systematic review. METHODS: Seventeen studies were identified from the PubMed, PsycInfo, Embase, Scopus, CINAHL, Web of Science and PILOTS databases. Effect size estimates (r) with associated 95% confidence intervals (CIs), P-values and fail-safe Ns were calculated. RESULTS: Individual studies reported medium-to-large associations between factors that occurred before (psychiatric history r=0.48 (95% CI, 0.23-0.79) P=0.01) or at the time of injury (tetraplegia r=-0.36 (95% CI, -0.50 to -0.19) P<0.01). Postinjury factors had the strongest pooled effects: depressed mood (rw=0.64, (95% CI, 0.54-0.72)), negative appraisals (rw=0.63 (95% CI, 0.52-0.72)), distress (rw=0.57 (95% CI, 0.50-0.62)), anxiety (rw=0.56 (95% CI, 0.49-0.61)) and pain severity (rw=0.35 (95% CI, 0.27-0.43)) were consistently related to worsening PTSD symptoms (P<0.01). Level of injury significantly correlated with current PTSD severity for veteran populations (QB (1)=18.25, P<0.001), although this was based on limited data. CONCLUSION: Combinations of peri- and post-injury factors appear to be influential in the development of PTSD among persons with SCI. Further studies are needed to extrapolate these findings to the broader spinal cord-injured population. More longitudinal research, driven by multicausal models of causation such as the diathesis-stress model, is also needed to determine the temporality of PTSD risk factors.

Decision-making and future planning for children with life-limiting conditions: a qualitative systematic review and thematic synthesis.

BACKGROUND: In the last decade, the number of children with life-limiting and life-threatening conditions in England has almost doubled, and it is estimated that worldwide, there are 1.2 million children with palliative care needs. Families and professionals caring for children with life-limiting conditions are likely to face a number of difficult treatment decisions and develop plans for future care over the course of the child's life, but little is known about the process by which these decisions and plans are made. METHODS: The purpose of this review is to synthesize findings from qualitative research that has investigated decision-making and future planning for children with life-limiting conditions. A systematic search of six online databases was conducted and identified 887 papers for review; five papers were selected for inclusion, using predefined criteria. Reference list searching and contacting authors identified a further four papers for inclusion. RESULTS: Results sections of the papers were coded and synthesized into themes. Nineteen descriptive themes were identified, and these were further synthesized into four analytical themes. Analytical themes were 'decision factors', 'family factors', 'relational factors' and 'system factors'. CONCLUSIONS: Review findings indicate that decision-making and future planning is difficult and needs to be individualized for each family. However, deficits in understanding the dynamic, relational and contextual aspects of decision-making remain and require further research.

Impact of partial bivalent HPV vaccination on vaccine-type infection: a population-based analysis.

BACKGROUND: Data on the effectiveness of one dose of HPV vaccine are lacking, particularly in population-based settings. Data from a national HPV immunisation catch-up programme of 14-18-year-old girls were used to assess the effectiveness of<3 doses of the bivalent vaccine on vaccine-type and cross-reactive-type HPV infection. METHODS: Cervical samples from women attending for their first cervical smear, which had been genotyped for HPV as part of a longitudinal HPV surveillance programme were linked to immunisation records to establish the number of vaccine doses (0, 1, 2 and 3) administered. Vaccine effectiveness (VE) adjusted for deprivation and age at first dose, was assessed for prevalent HPV 16/18 and HPV 31/33/45 infection. RESULTS: VE for prevalent HPV 16/18 infection associated with 1, 2 and 3 doses was 48.2% (95% CI 16.8, 68.9), 54.8% (95% CI 30.7, 70.8) and 72.8% (95% CI 62.8, 80.3). Equivalent VE for prevalent HPV 31/33/45 infection was -1.62% (95% CI -85.1, 45.3), 48.3% (95% CI 7.6, 71.8) and 55.2% (95% CI 32.6, 70.2). CONCLUSIONS: Consistent with recent aggregated trial data, we demonstrate the potential effectiveness of even one dose of HPV vaccine on vaccine-type infection. Given that these women were immunised as part of a catch-up campaign, the VE observed in this study is likely to be an underestimate of what will occur in girls vaccinated at younger ages. Further population-based studies which look at the clinical efficacy of one-dose schedules are warranted.

HPV immunisation and increased uptake of cervical screening in Scottish women; observational study of routinely collected national data.

BACKGROUND: To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign. METHODS: A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years. RESULTS: There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46-1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64-0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation. CONCLUSIONS: HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed.

HPV immunisation and cervical screening--confirmation of changed performance of cytology as a screening test in immunised women: a retrospective population-based cohort study.

BACKGROUND: To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP). METHODS: Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status. RESULTS: Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained. CONCLUSIONS: The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.

Adverse event monitoring of the human papillomavirus vaccines in Scotland.

BACKGROUND: Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. While evidence from clinical trials and epidemiological studies suggest that the HPV vaccines are both effective and safe, concerns about the safety of the vaccine and scientifically unproven associations with severe adverse events following immunisation have led to dramatic decreases in vaccine uptake in Japan and acceptance issues in other countries. AIM: In Scotland, we utilised hospital admissions data to assess the impact of the HPV immunisation programme on the incidence of 60 diagnoses between 2004 and 2014 in both girls and boys; with boys acting as a comparator group. METHODS: Tabular and graphical outputs of the number of admissions, the incidence and the incidence ratio of 59 diagnoses were created to assess trends before and after the introduction of the HPV vaccine. Data linkage was utilised to investigate further the increase in Bell palsy diagnoses. RESULTS: Fifty-four diagnoses showed no change in incidence following the introduction of the national immunisation programme, and while small increases in incidence were observed for Bell palsy, coeliac disease, ovarian dysfunction, juvenile onset of type 1 diabetes, demyelinating disease and juvenile rheumatoid arthritis, none was statistically significant. CONCLUSIONS: Consistent with previous evidence, we present disaggregate data that reiterate the safety of both HPV vaccines.

Molecular characterization of Cryptosporidium parvum isolates from human cryptosporidiosis cases in Scotland.

Cryptosporidium parvum (C. parvum) is one of the most prevalent protozoan pathogens responsible for inducing human and animal disease worldwide. In this study, the glycoprotein-60 (gp60) subtyping tool was employed to assess the molecular diversity of C. parvum from human feces throughout Scotland during potential outbreaks. Over a 24-month period, microscopy analysis revealed 1139 positive feces containing Cryptosporidium species with 256 identified by molecular methods specifically as C. parvum. Cryptosporidium parvum was shown to be more prevalent in rural areas of Scotland and subtyping of 87 isolates demonstrated the predominant family as IIa, which occurred in 94% (n=82) of isolates. The IIaA15G1R1 subtype was most common, being isolated from 47% (n=41) of Scottish human cases. Non-IIa strains constituted a total of 5 isolates and included subtypes from the IIc, IId and IIg families. This information contributes significantly to existing knowledge and understanding of C. parvum subtypes in Scotland which is vital in assisting with the management of future local and national outbreaks.

Validation of the sperm chromatin dispersion (SCD) test in the amphibian Xenopus laevis using in situ nick translation and comet assay.

The integrity of sperm DNA is becoming increasingly recognised as an important parameter of semen quality, but there are no published reports of this procedure for any amphibian. The primary aim of this study was to apply a modified sperm chromatin dispersion (SCD) test (Halomax) to an amphibian sperm model (African clawed frog; Xenopus laevis) and to validate the assay against in situ nick translation (ISNT) and the double-comet assay procedure. Inactivated spermatozoa were collected from fresh testes (n=3). Sperm DNA fragmentation (SDF) for each sperm sample was conducted immediately following activation (T0) and again after 1h (T1) and 24h (T24) of incubation at room temperature in order to produce a range of spermatozoa with differing levels of DNA damage. The SCD procedure resulted in the production of three nuclear morphotypes; amphibian sperm morphotype 1 (ASM-1) and ASM-2 showed no evidence of DNA damage, whereas ASM-3 spermatozoa were highly fragmented with large halos of dispersed DNA fragments and a reduced nuclear core. ISNT confirmed that ASM-3 nuclei contained damaged DNA. There was a significant correlation (r=0.9613) between the levels of ASM-3 detected by the SCD test and SDF revealed by the double-comet assay.