The design, implementation and evaluation of a laboratory based intervention to optimise serum immunoglobulin use in primary care

Background Laboratory testing plays a fundamental role in the screening, diagnoses and monitoring of many conditions. Given the increased pressures on the Irish health service, improving inefficiencies and reducing waste, while maintaining the quality of care is at the forefront of healthcare planning. Promoting optimal laboratory service utilisation could play a key role in reducing health expenditure, in particular by preventing the unnecessary use of costly downstream services that often arise as a result of testing. Aims and objectives The overall aim of this thesis was to design, implement and evaluate a behaviour change intervention for optimising serum immunoglobulin test use in primary care. The thesis objectives were as follows: 1. To conduct a systematic review of the existing literature on the effectiveness of previous interventions targeting primary care test use. 2. Identify the barriers and enablers of improving test ordering for serum immunoglobulins among General Practitioners (GPs), using semi-structured interviews. 3. Identify the intervention components (behaviour change techniques and mode(s) of delivery) that could overcome the modifiable barriers and enhance the enablers. 4. Determine which GP and practice characteristics are associated with higher serum immunoglobulin test ordering patterns in the South of Ireland. 5. To implement and evaluate a behaviour change intervention targeting GP serum immunoglobulin test use in the Cork-Kerry region. Structure and Methods The published literature to date was synthesised in a systematic review (Chapter 3). This review was conducted in accordance with the Effective Practice and Organisation of Care (EPOC) guidelines and quality appraised using the Cochrane Collaboration risk of bias tool. A theory-based paper identifying the modifiable barriers and enablers to test ordering behaviour change and the selection of intervention components to overcome these is presented in Chapter 4. This involved using a combination of behaviour change models including the Theoretical Domains Framework (TDF), the behaviour change wheel constructs; capabilities, opportunities, motivations of behaviour (COM-B) and Behaviour Change Techniques (BCTs) to identify intervention functions best suited to targeting GP test ordering behaviour. The GP and practice characteristics associated with higher test ordering patterns are described in Chapter 5. These were identified by performing a multi-level analysis of all GP test orders in the studied region for a one-year time period, using routine laboratory data. The design of the intervention material and details on the implementation plans are provided in Chapter 6. Results of the effect of the intervention using nine-month follow up data are described in Chapter 7. This was performed using interrupted time-series with segmented Poisson regression models to assess the pre-and xxi post-intervention trend for serum immunoglobulin testing among GPs in the Cork-Kerry region of Ireland. Finally, a discussion of the key findings, strengths and limitations of the thesis and recommendations for future research are addressed (Chapter 8). Key Findings A number of different interventions were of variable efficacy at changing GP test ordering behaviour. However, generalisability across tests and methodological weakness were identified in these studies (Chapter 3). GP factors contributing to higher immunoglobulin test ordering in our sample included female gender and fewer years of clinical experience (Chapter 5). The lack of clear guidelines and knowledge on how to interpret the test results posed greatest problems for GPs. Four key intervention functions were identified for overcoming these modifiable barriers to effective test use; education, persuasion, enablement and environmental restructuring (Chapter 4). Following the introduction of a guideline and education-based strategy targeting the two key issues (by incorporating the four functions), test orders for serum immunoglobulins dropped significantly. A nine-month evaluation of the effectiveness of this intervention found a statistically significant 1.5% reduction in the fortnight-to-fortnight test ordering trend for serum immunoglobulins (Chapter 7). Conclusions This research provides an important overview of the behavioural factors influencing laboratory testing among GPs. The incorporation of behavioural theory, specifically the COM-B, TDF and BCT taxonomy, has supported the identification of factors such as xxii knowledge and the social and environmental context, which are key for understanding testing behaviours. Combining these context specific "mechanisms of change" with international evidence on what has previously worked, assisted in the development of an effective behaviour change intervention targeting serum immunoglobulin test use in primary care

Prevalence of and factors associated with herpes zoster in England: a cross-sectional analysis of the Health Survey for England

BACKGROUND: Herpes zoster (commonly called shingles) is caused by the reactivation of varicella zoster virus, and results in substantial morbidity. While the risk of zoster increases significantly with age and immunosuppression, relatively little is known about other risk factors for zoster. Moreover, much evidence to date stems from electronic healthcare or administrative data. Hence, the aim of this study was to explore potential risk factors for herpes zoster using survey data from a nationally-representative sample of the general community-dwelling population in England. METHODS: Data were extracted from the 2015 Health Survey for England, an annual cross-sectional representative survey of households in England. The lifetime prevalence of self-reported herpes zoster was described by age, gender and other socio-demographic factors, health behaviours (physical activity levels, body mass index, smoking status and alcohol consumption) and clinical conditions, including; diabetes, respiratory, digestive and genito-urinary system and mental health disorders. Logistic regression models were then used to identify possible factors associated with shingles, and results were presented as odds ratios with 95% confidence intervals. RESULTS: The lifetime prevalence of shingles among the sample was 11.5% (12.6% among women, 10.3% among men), which increased with age. After adjusting for a range of covariates, increased age, female gender (odds ratio: 1.21; 95%CI: 1.03, 1.43), White ethnic backgrounds (odds ratio: 2.00; 95%CI: 1.40, 2.88), moderate physical activity 7 days per week (odds ratio: 1.29; 95%CI: 1.01, 1.66) and digestive disorders (odds ratio: 1.51; 95%CI: 1.13, 1.51) were each associated with increased odds of having had herpes zoster. CONCLUSIONS: Age, gender, ethnicity and digestive disorders may be risk factors for herpes zoster among a nationally representative sample of adults in England. These potential risk factors and possible mechanisms should be further explored using longitudinal studies

The effects of individual, family and environmental factors on physical activity levels in children: a cross-sectional study.

BACKGROUND: Physical activity plays an important role in optimising physical and mental health during childhood, adolescence, and throughout adult life. This study aims to identify individual, family and environmental factors that determine physical activity levels in a population sample of children in Ireland. METHODS: Cross-sectional analysis of the first wave (2008) of the nationally representative Growing Up in Ireland study. A two-stage clustered sampling method was used where national schools served as the primary sampling unit (response rate: 82%) and age eligible children from participating schools were the secondary units (response rate: 57%). Parent reported child physical activity levels and potential covariates (parent and child reported) include favourite hobby, total screen time, sports participation and child body mass index (measured by trained researcher). Univariate and multivariate multinomial logistic regression (forward block entry) examined the association between individual, family and environmental level factors and physical activity levels. RESULTS: The children (N = 8,568) were classified as achieving low (25%), moderate (20%) or high (55%) physical activity levels. In the fully adjusted model, male gender (OR 1.64 [95% CI: 1.34-2.01]), having an active favourite hobby (OR 1.65 [95% CI: 1.31-2.08]) and membership of sports or fitness team (OR 1.90 [95% CI: 1.48-2.45]) were significantly associated with being in the high physical activity group. Exceeding two hours total screen time (OR 0.66 [95% CI: 0.52-0.85]), being overweight (OR 0.41 [95%CI: 0.27-0.61]; or obese (OR 0.68 [95%CI: 0.54-0.86]) were significantly associated with decreased odds of being in the high physical activity group. CONCLUSIONS: Individual level factors appear to predict PA levels when considered in the multiple domains. Future research should aim to use more robust objective measures to explore the usefulness of the interconnect that exists across these domains. In particular how the family and environmental settings could be useful facilitators for consistent individual level factors such as sports participation

Prevalence of and factors associated with herpes zoster in England: a cross-sectional analysis of the Health Survey for England.

BACKGROUND: Herpes zoster (commonly called shingles) is caused by the reactivation of varicella zoster virus, and results in substantial morbidity. While the risk of zoster increases significantly with age and immunosuppression, relatively little is known about other risk factors for zoster. Moreover, much evidence to date stems from electronic healthcare or administrative data. Hence, the aim of this study was to explore potential risk factors for herpes zoster using survey data from a nationally-representative sample of the general community-dwelling population in England. METHODS: Data were extracted from the 2015 Health Survey for England, an annual cross-sectional representative survey of households in England. The lifetime prevalence of self-reported herpes zoster was described by age, gender and other socio-demographic factors, health behaviours (physical activity levels, body mass index, smoking status and alcohol consumption) and clinical conditions, including; diabetes, respiratory, digestive and genito-urinary system and mental health disorders. Logistic regression models were then used to identify possible factors associated with shingles, and results were presented as odds ratios with 95% confidence intervals. RESULTS: The lifetime prevalence of shingles among the sample was 11.5% (12.6% among women, 10.3% among men), which increased with age. After adjusting for a range of covariates, increased age, female gender (odds ratio: 1.21; 95%CI: 1.03, 1.43), White ethnic backgrounds (odds ratio: 2.00; 95%CI: 1.40, 2.88), moderate physical activity 7 days per week (odds ratio: 1.29; 95%CI: 1.01, 1.66) and digestive disorders (odds ratio: 1.51; 95%CI: 1.13, 1.51) were each associated with increased odds of having had herpes zoster. CONCLUSIONS: Age, gender, ethnicity and digestive disorders may be risk factors for herpes zoster among a nationally representative sample of adults in England. These potential risk factors and possible mechanisms should be further explored using longitudinal studies

Needle size for vaccination procedures in children and adolescents

Background: This is an update of a Cochrane Review first published in 2015. The conclusions have not changed. Hypodermic needles of different sizes (gauges and lengths) can be used for vaccination procedures. The gauge (G) refers to the outside diameter of the needle tubing. The higher the gauge number, the smaller the diameter of the needle (e.g. a 23 G needle is 0.6 mm in diameter, whereas a 25 G needle is 0.5 mm in diameter). Many vaccines are recommended for injection into muscle (intramuscularly), although some are delivered subcutaneously (under the skin) and intradermally (into skin). Choosing an appropriate length and gauge of a needle may be important to ensure that a vaccine is delivered to the appropriate site and produces the maximum immune response while causing the least possible harm. Guidelines conflict regarding the sizes of needles that should be used for vaccinating children and adolescents. Objectives: To assess the effects of using needles of different sizes for administering vaccines to children and adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an immune response), procedural pain, and other reactogenicity events (adverse events following vaccine administration). Search methods: We updated our searches of CENTRAL, MEDLINE, Embase, and CINAHL to October 2017. We also searched proceedings of vaccine conferences and two trials registers. Selection criteria: Randomised controlled trials evaluating the effects of using hypodermic needles of any gauge or length to administer any type of vaccine to people aged from birth to 24 years. Data collection and analysis: Three review authors independently extracted trial data and assessed the risk of bias. We contacted trial authors for additional information. We rated the quality of evidence using the GRADE system. Main results: We included five trials involving 1350 participants in the original review. The updated review identified no new trials. The evidence from two small trials (one trial including infants and one including adolescents) was insufficient to allow any definitive statements to be made about the effects of the needles evaluated in the trials on vaccine immunogenicity and reactogenicity. The remaining three trials (1135 participants) contributed data to comparisons between 25 G 25 mm, 23 G 25 mm, and 25 G 16 mm needles. These trials included infants predominantly aged from two to six months undergoing intramuscular vaccination in the anterolateral thigh using the World Health Organization (WHO) injection technique (skin stretched flat, needle inserted at a 90° angle and up to the needle hub in healthy infants). The vaccines administered were combination vaccines containing diphtheria, tetanus, and whole‐cell pertussis antigens (DTwP). In some trials, the vaccines also contained Haemophilus influenzae type b (DTwP‐Hib) and hepatitis B (DTwP‐Hib‐Hep B) antigen components. Primary outcomes: Incidence of vaccine‐preventable diseases: No trials reported this outcome. Procedural pain and crying: Using a wider gauge 23 G 25 mm needle may slightly reduce procedural pain (low‐quality evidence) and probably leads to a slight reduction in the duration of crying time immediately after vaccination (moderate‐quality evidence) compared with a narrower gauge 25 G 25 mm needle (one trial, 320 participants). The effects are probably not large enough to be clinically relevant…Authors' conclusions: Using 25 mm needles (either 23 G or 25 G) for intramuscular vaccination procedures in the anterolateral thigh of infants using the WHO injection technique probably reduces the occurrence of local reactions while achieving a comparable immune response to 25 G 16 mm needles. These findings are applicable to healthy infants aged two to six months receiving combination DTwP vaccines with a reactogenic whole‐cell pertussis antigen component. These vaccines are predominantly used in low‐ and middle‐income countries. The applicability of the findings to vaccines with acellular pertussis components and other vaccines with different reactogenicity profiles is uncertain

COVID-19 collateral: Indirect acute effects of the pandemic on physical and mental health in the UK

ABSTRACTBackgroundConcerns have been raised that the response to the UK COVID-19 pandemic may have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We asked what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic?MethodsUsing electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (2017-2020), we calculated weekly primary care contacts for selected acute physical and mental health conditions (including: anxiety, depression, acute alcohol-related events, asthma and chronic obstructive pulmonary disease [COPD] exacerbations, cardiovascular and diabetic emergencies). We used interrupted time series (ITS) analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (‘lockdown’) compared to the period prior to their introduction in March 2020.FindingsThe overall population included 9,863,903 individuals on 1st January 2017. Primary care contacts for all conditions dropped dramatically after introduction of population-wide restrictions. By July 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. The largest reductions were for contacts for: diabetic emergencies (OR: 0.35, 95% CI: 0.25-0.50), depression (OR: 0.53, 95% CI: 0.52-0.53), and self-harm (OR: 0.56, 95% CI: 0.54-0.58).InterpretationThere were substantial reductions in primary care contacts for acute physical and mental conditions with restrictions, with limited recovery by July 2020. It is likely that much of the deficit in care represents unmet need, with implications for subsequent morbidity and premature mortality. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people experiencing the conditions and healthcare provision. Maintaining access must be a key priority in future public health planning (including further restrictions).FundingWellcome Trust Senior Fellowship (SML), Health Data Research UK.RESULTS IN CONTEXTEvidence before this studyA small study in 47 GP practices in a largely deprived, urban area of the UK (Salford) reported that primary care consultations for four broad diagnostic groups (circulatory disease, common mental health problems, type 2 diabetes mellitus and malignant cancer) declined by 16-50% between March and May 2020, compared to what was expected based on data from January 2010 to March 2020. We searched Medline for other relevant evidence of the indirect effect of the COVID-19 pandemic on physical and mental health from inception to September 25th 2020, for articles published in English, with titles including the search terms (“covid*” or “coronavirus” or “sars-cov-2”), and title or abstracts including the search terms (“indirect impact” or “missed diagnos*” or “missing diagnos*” or “delayed diagnos*” or ((“present*” or “consult*” or “engag*” or “access*”) AND (“reduction” or “decrease” or “decline”)). We found no further studies investigating the change in primary care contacts for specific physical- and mental-health conditions indirectly resulting from the COVID-19 pandemic or its control measures. There has been a reduction in hospital admissions and presentations to accident and emergency departments in the UK, particularly for myocardial infarctions and cerebrovascular accidents. However, there is no published evidence specifically investigating the changes in primary care contacts for severe acute physical and mental health conditions.Added value of this studyTo our knowledge this is the first study to explore changes in healthcare contacts for acute physical and mental health conditions in a large population representative of the UK. We used electronic primary care health records of nearly 10 million individuals across the UK to investigate the indirect impact of COVID-19 on primary care contacts for mental health, acute alcohol-related events, asthma/chronic obstructive pulmonary disease (COPD) exacerbations, and cardiovascular and diabetic emergencies up to July 2020. For all conditions studied, we found primary care contacts dropped dramatically following the introduction of population-wide restriction measures in March 2020. By July 2020, with the exception of unstable angina and acute alcohol-related events, primary care contacts for all conditions studied had not recovered to pre-lockdown levels. In the general population, estimates of the absolute reduction in the number of primary care contacts up to July 2020, compared to what we would expect from previous years varied from fewer than 10 contacts per million for some cardiovascular outcomes, to 12,800 per million for depression and 6,600 for anxiety. In people with COPD, we estimated there were 43,900 per million fewer contacts for COPD exacerbations up to July 2020 than what we would expect from previous years.Implicatins of all the available evidenceWhile our results may represent some genuine reduction in disease frequency (e.g. the restriction measures may have improved diabetic glycaemic control due to more regular daily routines at home), it is more likely the reduced primary care conatcts we saw represent a substantial burden of unmet need (particularly for mental health conditions) that may be reflected in subsequent increased mortality and morbidity. Health service providers should take steps to prepare for increased demand in the coming months and years due to the short and longterm ramifications of reduced access to care for severe acute physical and mental health conditions. Maintaining access to primary care is key to future public health planning in relation to the pandemic.</jats:sec

Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.

BACKGROUND: There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic. METHODS: Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28). FINDINGS: The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. INTERPRETATION: There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision. FUNDING: Wellcome Trust Senior Fellowship, Health Data Research UK

Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. RESULTS: There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. INTERPRETATION: We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD

The Impact of Indonesia’s Tobacco Control Policy on Cigarette Smoking Among Indonesian Adults: A Longitudinal Study

Introduction The Indonesian government has introduced tobacco control policies corresponding to MPOWER since 2007. However, the impact of these measures on trends of cigarette smoking behaviour among Indonesian adults remains scarcely investigated. This study assessed the changes in smoking cessation and initiation among Indonesian adults and identified associated socioeconomic determinants before and after the adoption of MPOWER in Indonesia tobacco control strategy. Methods A longitudinal study was conducted to analyse Indonesian adults (aged 15 years and above) data from two waves of Indonesian Family Life Survey (IFLS) in 2007 (n= 13,535 households; 44,103 individuals) and 2014 (n=16,204 households; 50,148 individuals). Regression analyses were performed to identify the socioeconomic factors associated with the change in smoking status - quit smoking and smoking initiation - occurred between 2007 and 2014. Results There were 22,765 followed-up respondents identified as longitudinal sample. A significant rise in the current smoker prevalence from 30.6% in 2007 to 31.0% in 2014 (p<0.01) was observed. The proportion of smokers in 2007 who quit by 2014 was 8.0% while the proportion of non-smokers in 2007 who initiated smoking by 2014 was 6.4%. Smoking cessation between 2007 and 2014 was positively associated with education (aOR:2.14; 95%CI 1.43, 3.06 for university graduates) and wealth (aOR: 1.60; 95%CI 1.23, 2.09 for the richest group) while, conversely, those with higher education levels and wealth status had lower odds (aOR: 0.81; 95%CI 0.63, 1.02 and aOR: 0.49; 95%CI 0.41, 0.57 respectively) of initiating smoking within the period. Conclusions The implementation of tobacco control measures in Indonesia was unsuccessful to reduce the cigarette use among adults between 2007 and 2014. Furthermore, the policies have unequally affected subgroups of the population. Therefore, the government is urged to formulate target-specific tobacco control efforts. Funding The travel grant for the conference will be funded by La Caixa INPhINIT Fellowships programm