Strengthening HPV vaccination delivery: findings from a qualitative service evaluation of the adolescent girls' HPV vaccination programme in England.

BACKGROUND: In 2014, the number of HPV vaccine doses given to adolescent girls as part of the English school-based immunization programme was reduced from three to two. This was based on evidence that a two-dose schedule provides long-lasting protection against HPV infection. In 2015/16 a small decline in HPV vaccination coverage in adolescent girls was noted; from 86.7% for the three-dose schedule in 2013/14 to 85.1% for the two-dose schedule. This evaluation examined whether service-related factors contributed to this decline. METHODS: In May-August 2017, we conducted semi-structured qualitative interviews with 39 participants responsible for commissioning or delivering immunization programmes in six local authorities in the South West, North Central Midlands and South Central Midlands, England. RESULTS: Effective planning and data management were key for successful service provision of HPV vaccination, as well as close collaboration between commissioners, service providers and data system managers, a team skill mix with experienced staff, pro-active engagement with schools and service providers equipped to respond to parental concerns. CONCLUSIONS: To maintain and improve the high HPV adolescent girls' vaccine coverage rates achieved in England, in the context of an expanding school-based immunization programme, it is essential to strengthen the organizational capacity of the delivery system.

School-based vaccination programmes: An evaluation of school immunisation delivery models in England in 2015/16.

Schools are increasingly being used to deliver vaccines. In 2015/16 three school-based vaccination programmes were delivered to adolescents in England: human papillomavirus (HPV), meningococcal groups A, C, W and Y disease (MenACWY) and tetanus, diphtheria and polio (Td/IPV). We assessed how school delivery models impact vaccine coverage and how a delivery model for one programme may impact another. Routinely collected national data were analysed to ascertain the school grade achieving highest coverage within each one-dose programme and to compare two-dose delivery models (within year vs across years) for the HPV vaccine. We also assessed whether the HPV delivery model was associated with coverage in other programmes. MenACWY and Td/IPV coverage was highest in younger school grades. Overall similar HPV coverage was achieved with both models (86.7% two doses within one year, 85.8% two doses across two years, p = 0.20). High two-dose HPV coverage in 2015/16 was reported in areas that achieved high HPV coverage in 2013/14 when three doses were required. Areas with high three-dose coverage in 2013/14 achieved higher coverage with a within-one-year approach (92.0% vs 85.2%, p < 0.001), whilst areas reporting low coverage in 2013/14 achieved lower but similar coverage in 2015/16 with both models (79.2% vs 80.9% p = 0.29). MenACWY and Td/IPV coverage were higher in areas with high HPV coverage in 2013/14. Among high HPV coverage areas, MenACWY coverage was higher when HPV doses were delivered within year. School-based programmes should be offered as early as feasible and acceptable to optimise coverage. The choice of delivery model for HPV should take into account local performance and provider experience. Single providers may delivery multiple vaccines and the delivery for one programme may affect the performance of other programmes. Providers should consider local circumstances including past and current vaccine coverage and factors influencing coverage when deciding what delivery model to adopt.

Monitoring liver transplant rates in persons diagnosed with hepatitis C: a data linkage study, England 2008 to 2017.

IntroductionLiver transplantation is an important measure of burden from hepatitis C virus (HCV)-associated liver disease.AimsTo describe transplant rates and survival in individuals with HCV infection from 2008 to 2017 in England through data linkage.MethodsThis is a retrospective observational cohort study. Laboratory reports of HCV infection were linked to the Liver Transplant Registry for individuals aged 15 years and over, first diagnosed between 1998 and 2017. We estimated age-sex standardised incidence rates and used Poisson regression to investigate predictors of liver transplantation and test for a change in incidence after introduction of direct-acting antivirals (DAAs) in 2014. Kaplan-Meier survival analysis was used to calculate post-transplant survival rates.ResultsOf 124,238 individuals diagnosed with HCV infection, 1,480 were registered and 1,217 received a liver transplant. Of individuals registered, 1,395 had post-HCV cirrhosis and 636 had hepatocellular carcinoma (618 also had post-HCV cirrhosis). Median time from HCV diagnosis to transplant was 3.4 years (interquartile range: 1.3-6.8 years). Liver transplant rates were lower 2014-17 compared with 2011-13 (incidence rate ratio: 0.64; 95% confidence interval: 0.55-0.76). Survival rates were 93.4%, 79.9% and 67.9% at 1, 5 and 10 years, respectively. Data linkage showed minimal under-reporting of HCV in the transplant registry.ConclusionIn the post-DAA era, liver transplant rates have fallen in individuals with HCV infection, showing early impact of HCV treatment scale-up; but the short time from HCV diagnosis to liver transplant suggests late diagnosis is a problem.

Strengthening human genetics research in Africa: report of the 9th meeting of the African Society of Human Genetics in Dakar in May 2016.

The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.

Le 9ème congrès de la Société Africaine de Génétique Humaine, en partenariat avec le Groupe d'Etude et de Recherche sur le Cancer (GERC) et le Consortium H3Africa, s'est tenu à Dakar, au Sénégal. Le thème était «Renforcer la recherche en Génétique Humaine en Afrique¼. Les 210 participants sont venus de 21 pays africains et de six non africains. L'objectif était de valoriser la génétique et la génomique à travers l'Afrique avec comme but ultime d'améliorer la santé des populations, et de promouvoir les carrières des jeunes chercheurs Africains. Une session sur la pérennité de la recherche génomique a révélé des approches innovantes et pratiques supportant la recherche dans des contextes de ressources limitées et l'importance de promouvoir la formation universitaire en génétique, le financement de la recherche par les gouvernements et le privé. Ce congrès conduisit à la création de la Société Sénégalaise de Génétique Humaine.

New treatments for hepatitis C virus (HCV): scope for preventing liver disease and HCV transmission in England.

New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.

Intravenous dexmedetomidine as an adjunct for labor analgesia and cesarean delivery anesthesia in a parturient with a tethered spinal cord.

For parturients desiring labor analgesia who have contraindications to neuraxial techniques, intravenous opioid-based patient-controlled analgesia (IVPCA) offers a reasonable alternative, although incomplete analgesia and maternal and neonatal respiratory depression can occur. Dexmedetomidine, a highly selective alpha(2) agonist with negligible placental transfer, may be a valuable adjunct to IVPCA by providing additional analgesia without the respiratory depression associated with increasing opioid usage. The successful use of a dexmedetomidine infusion as an adjunct to unsatisfactory fentanyl IVPCA is reported in a 31-year-old parturient with spina bifida occulta and a tethered spinal cord reaching L5-S1. Dexmedetomidine significantly improved the analgesic quality; increased sedation was observed, but the patient was easily rousable to verbal stimuli. No episodes of maternal hypotension or bradycardia, or fetal heart rate irregularities occurred. Cesarean delivery was required for prolonged first stage of labor and presumed chorioamnionitis; it was conducted under general anesthesia during which the dexmedetomidine infusion was continued. A healthy baby boy was delivered with normal Apgar scores and no discernible neurobehavioral or other deficits.

Hepatitis C in ethnic minority populations in England.

The aim of the study was to investigate the differing epidemiology of hepatitis C-related end-stage liver disease in ethnic minorities in England. We used Hospital Episode Statistics from 1997/98 to 2004/05 to directly age-standardize numbers of episodes and deaths from hepatitis C-related end-stage liver disease in ethnic groups using the white English population as standard and the age-structured population by ethnic group from the 2001 Census. We estimated the odds of having a diagnosis of end-stage liver disease amongst hepatitis C-infected individuals in each ethnic group compared with whites using logistic regression. The main outcome measures were age-standardized morbidity and mortality ratios and morbidity and mortality odds ratios. Standardized ratios (95% confidence interval) for hepatitis C-related end-stage liver disease ranged from 73 (38-140) in Chinese people to 1063 (952-1186) for those from an 'Other' ethnic group. Amongst individuals with a diagnosis of hepatitis C infection, the odds ratios (95% CI) of severe liver disease were 1.42 (1.13-1.79), 1.57 (1.36-1.81), 2.44 (1.85-3.22), 1.73 (1.36-2.19) and 1.83 (1.08-3.10) comparing individuals of Black African, Pakistani, Bangladeshi, Indian and Chinese origin with whites, respectively. Ethnic minority populations in England are more likely than whites to experience an admission or to die from severe liver disease as a result of hepatitis C infection. Ethnic minority populations may have a higher prevalence of hepatitis C or they may experience a poorer prognosis because of differential access to health services, longer duration of infection or the prevalence of co-morbidities.

The burden of hepatitis C in England.

In England, a large number of individuals are infected with the hepatitis C virus (HCV) and may develop future liver complications, such as decompensated cirrhosis and hepatocellular carcinoma (HCC). Estimates of the magnitude of this future burden are required to plan healthcare resources. We have estimated past incidence of HCV infection in England and predict future burden of end-stage liver disease in the HCV-infected population. A model of the natural history of HCV as a series of disease stages was constructed. A back-calculation approach was performed, using the natural history model and data on annual HCC deaths in England from 1996 to 2004 with mention of HCV and hospital episode statistics for end-stage liver disease with HCV. The number of HCV-infected people living with compensated cirrhosis is predicted to rise from 3705 [95% credible interval (CrI): 2820-4975] in 2005 to 7550 (95% CrI: 5120-11,640) in 2015. The number of decompensated cirrhosis and/or HCC cases is also predicted to rise, to 2540 (95% CrI: 2035-3310) by 2015. HCV incidence increased during the 1980s, with an annual incidence of 12 650 (95% CrI: 6150-26,450) by 1989. HCV-related cirrhosis and deaths from HCC in England are likely to increase dramatically within the next decade. If patients are left undiagnosed and untreated, the future burden of the disease on healthcare resources will be substantial.

Pathways of care and resource utilization in a national cohort of patients with transfusion-acquired hepatitis C.

The Hepatitis C Strategy and Action Plan for England recommend that all individuals testing positive for hepatitis C virus (HCV) should be referred to a specialist centre for assessment and care. One key aim is to reduce the number of people progressing to liver disease and therefore reduce the associated costs. The aims of this paper are to describe the care pathways and evaluate resource utilization in a cohort of 826 patients with transfusion-acquired hepatitis C enrolled in the HCV national register. We reviewed data extracted from patient notes to establish pathways of care since HCV-positive diagnosis through to May 2002, and to document all treatment, liver biopsy and hospital usage for each patient. Type of care was classified into specialist-interest in HCV-related care, other-hospital care or general practitioner (GP)-led care. Over 70% of patients were referred to specialist care following HCV diagnosis. Patients who were older or who had normal liver function were less likely to be referred to specialist-care. Between first diagnosis and May 2002, no patients were referred from GP to specialist-care. Less than half of this cohort had undergone liver biopsy and only 18% had been treated. Younger patients and those with abnormal liver function were more likely to have undergone liver biopsy and to have received treatment. Analysis of care histories of patients with transfusion-acquired hepatitis C suggest that changes are needed in the care and management of patients with HCV infection, if the recommendations of the HCV strategy and action plan are to be fully implemented.

Description of a technique for anaesthetizing pregnant ewes for fetal surgery.

General anaesthesia in 12 pregnant ewes undergoing surgery for fetal physiological research was supplemented with an intravenous infusion of remifentanil. This allowed us to employ a lighter plane of surgical anaesthesia and to use intermittent positive pressure ventilation. Our aim was to improve fetomaternal outcome. We monitored maternal pulse, blood pressure, transcutaneous oxygen saturation and end-tidal carbon dioxide levels. Remifentanil doses of 0.75-2.0 microg/kg/min were needed and typically this allowed halothane concentrations of 1-1.5% to be used for maintenance of anaesthesia. Surgery lasted up to 2.5 h. All 12 ewes and their singleton fetuses survived the peri- and postoperative period in good condition.

Megestrol acetate promotes euglycemia and appetite in a child with persistent hyperinsulinemic hypoglycemia of infancy.

UNLABELLED: This report describes a successful treatment with megestrol acetate in a child with persistent hyperinsulinemic hypoglycemia of infancy (PHHI). An 8-y-old child with PHHI treated with octreotide had marked impairment of appetite sensation and feeding skills. Within 3 wk of starting megestrol acetate (8 mg/kg/d) to stimulate her appetite, she had a significant improvement. By 1 y postinitiation, she had acquired age-appropriate eating habits. The megestrol acetate caused hyperglycemia, necessitating the discontinuation of all other therapy for her hypoglycemia. Her height growth remained normal but she was found to have asymptomatic adrenal suppression. CONCLUSION: Megestrol acetate appeared to stimulate appetite and regulate glucose homeostasis in this child with PHHI. Additional studies will be required to document its efficacy and safety in other children with this disorder.

Causes of morbilliform rash in a highly immunised English population.

AIMS: To determine the causes of morbilliform rash and fever in a population with high vaccination coverage for measles and rubella. METHODS: Comprehensive laboratory investigation additional to routine oral fluid testing of children presenting to primary care physicians in East Anglia, England. RESULTS: Laboratory confirmation of infection was obtained in 93 (48%) of 195 children: parvovirus B19 in 34 (17%); group A streptococcus in 30 (15%); human herpesvirus type 6 in 11 (6%); enterovirus in nine (5%); adenovirus in seven (4%); and group C streptococcus in six (3%) (four individuals tested positive for two agents). None had measles or rubella. CONCLUSIONS: Oral fluid testing to cover infections additional to measles and rubella aids clinical management and is likely to maintain uptake of testing, which is essential for measles and rubella surveillance in highly immunised low incidence populations.

The molecular basis of cystic fibrosis in South Africa.

The spectrum of CFTR mutations in three South African populations is presented. To date. a total of 192 white patients (384 chromosomes) with confirmed CF have been tested. deltaF508 accounts for 76% of the CF chromosomes in this group, with 3272-26A-->G, 394delTT and G542X occurring at the following frequencies: 4, 3.6 and 1.3%, respectively. A further 11 mutations account for 6% of CF chromosomes. A total of 91% of the CF-causing mutations can now be detected in the South African white population. Haplotype analysis suggests a founder effect in South Africans of European origin for the two common CFTR mutations, 3272-26A-->G and 394delTT. The diagnosis of CF has been confirmed in 14 coloured and 12 black CF patients. In the coloured population, both the deltaF508 and 3120 + 1G-->A mutations occur at appreciable frequencies of 43 and 29%, respectively. In the black population, the most common CF-causing mutation, the 3120 + 1G-->A mutation, occurs at an estimated frequency of 46%. Four other mutations have been detected, resulting in the identification of a total of 62.5% of mutations in this population.

Second dose of measles, mumps, and rubella vaccine: questionnaire survey of health professionals.

OBJECTIVE: To determine the knowledge, attitudes, and practices among health professionals regarding the measles, mumps, and rubella (MMR) vaccine, particularly the second dose. DESIGN: Self administered postal questionnaire survey. SETTING: North Wales Health Authority, 1998. PARTICIPANTS: 148 health visitors, 239 practice nurses, and 206 general practitioners. MAIN OUTCOME MEASURES: Respondents' views on MMR vaccination, including their views on the likelihood of an association with autism and Crohn's disease and on who is the best person to give advice to parents, whether they agree with the policy of a second dose of the vaccine, and how confident they are in explaining the rationale behind the second dose. RESULTS: Concerning the second dose of the vaccine, 48% of the professionals (220/460) had reservations and 3% (15) disagreed with the policy of giving it. Over half the professionals nominated health visitors as the best initial source of advice on the second vaccine. 61% of health visitors (86/140), compared with 46% of general practitioners (73/158), reported feeling very confident about explaining the rationale of a two dose schedule to a well informed parent, but only 20% (28/138) would unequivocally recommend the second dose to a wavering parent. 33% of the practice nurses (54/163) stated that the MMR vaccine was very likely or possibly associated with Crohn's disease and 27% (44/164) that it was associated with autism. Nearly a fifth of general practitioners (27/158) reported that they had not read the MMR section in the "green book," and 29% (44/152) reported that they had not received the Health Education Authority's factsheet on MMR immunisation. CONCLUSIONS: Knowledge and practice among health professionals regarding the second dose of the MMR vaccine vary widely. Many professionals are not aware of or do not use the good written resources that exist, though local educational initiatives could remedy this.

The HCV National Register: towards informing the natural history of hepatitis C infection in the UK.

The aim of this paper is to describe the development of a national hepatitis C register and the completeness of the data it contains. This is a descriptive report of the structure and function of the register, including case definitions, registration and follow-up procedures, and methods used to maximize data quality and to obtain comparative data sources. The register contains data on HCV-infected individuals who acquired their infections on a known date and by a known route; to date all are transfusion recipients identified during the UK lookback exercise, who tested positive or indeterminate for anti-HCV after receiving 'infected' blood issued before the introduction of routine testing of the blood supply for anti-HCV. By 31 December 1999, 871 (87%) of 996 eligible transfusion recipients had been registered, and 984 (99%) flagged in the NHS Central Registers. Registered patients had been infected for an average of 11.1 years (SEM 0.1); around half were being cared for by clinicians with a specialist interest in liver disease. Except for the information on tobacco use, current alcohol use, and hepatitis B status, data were more than 80% complete, and for most variables, more than 90% complete. The consistency of data abstraction was found to be 98% (SEM 0.5). In conclusion, the Register contains high quality anonymised data on one of the largest cohorts of individuals with HCV infections acquired on a known date and by a known route. It could serve as a model for other chronic disease registers; developers may find the structure, design, and methodological issues addressed useful.

Prenatal diagnosis of congenital Wilms' tumor (nephroblastoma) presenting as fetal hydrops.

We describe a case of congenital nephroblastoma (Wilms' tumor) presenting at 28 weeks of gestation with fetal hydrops and polyhydramnios. Prenatal diagnosis was made by biopsy. An emergency Cesarean section was performed due to deterioration in the cardiotocograph. A post-mortem examination confirmed the diagnosis of congenital nephroblastoma.

A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease.

Glucocorticoids remain the standard approach to initial systemic management of acute graft-versus-host disease (aGVHD). For patients refractory to steroids, antithymocyte globulin (ATG) is frequently used as salvage therapy. We decided to test whether the combination of corticosteroids and equine ATG would improve the outcome of initial management of aGVHD, especially in high-risk patients such as recipients of unrelated donor (URD) transplants. One hundred patients with grade II to IV aGVHD having undergone a related or URD marrow transplant were enrolled in the study. Of the patients, 46 were randomly assigned to therapy with prednisone (60 mg/m2 per day x 7 days) and 50 received ATG/prednisone (15 mg/kg ATG bid plus 20 mg/m2 prednisone bid x 5 days, each followed by an 8-week prednisone taper). An intent-to-treat analysis of the overall response at day 42 revealed equivalent complete plus partial response rates of 76% in both the prednisone and ATG/prednisone therapy groups (P > .80). In univariate analysis, patient age, donor type, site of involvement, or aGVHD stage did not influence overall response to therapy (all P > .2). When treatment arms were studied separately, no single clinical feature predicted outcome in either group. Complications were more frequent in the ATG/prednisone arm; patients experienced more infections with cytomegalovirus (44% versus 22%; P = .02) and more frequent pneumonitis, both infectious and noninfectious (50% versus 24%; P < .01). Epstein-Barr virus lymphoproliferative disease was uncommon (4 cases) and comparable in both arms (P = .35). There was no significant difference in survival at day 100, 6 months, and 2 years between the 2 treatment arms. The more intensive immunosuppressive combination of ATG/prednisone failed to improve control of aGVHD and may have affected survival by causing more infectious complications. Combination therapy with ATG should thus be reserved as second-line therapy in the management of aGVHD.