Expanding the Evidence on the Safety and Efficiency of 2-Way Text Messaging-Based Telehealth for Voluntary Medical Male Circumcision Follow-up Compared With In-Person Reviews: Randomized Controlled Trial in Rural and Urban South Africa.

BACKGROUND: There is a dearth of high-quality evidence from digital health interventions in routine program settings in low- and middle-income countries. We previously conducted a randomized controlled trial (RCT) in Zimbabwe, demonstrating that 2-way texting (2wT) was safe and effective for follow-up after adult voluntary medical male circumcision (VMMC). OBJECTIVE: To demonstrate the replicability of 2wT, we conducted a larger RCT in both urban and rural VMMC settings in South Africa to determine whether 2wT improves adverse event (AE) ascertainment and, therefore, the quality of follow-up after VMMC while reducing health care workers' workload. METHODS: A prospective, unblinded, noninferiority RCT was conducted among adult participants who underwent VMMC with cell phones randomized in a 1:1 ratio between 2wT and control (routine care) in North West and Gauteng provinces. The 2wT participants responded to a daily SMS text message with in-person follow-up only if desired or an AE was suspected. The control group was requested to make in-person visits on postoperative days 2 and 7 as per national VMMC guidelines. All participants were asked to return on postoperative day 14 for study-specific review. Safety (cumulative AEs ≤day 14 visit) and workload (number of in-person follow-up visits) were compared. Differences in cumulative AEs were calculated between groups. Noninferiority was prespecified with a margin of -0.25%. The Manning score method was used to calculate 95% CIs. RESULTS: The study was conducted between June 7, 2021, and February 21, 2022. In total, 1084 men were enrolled (2wT: n=547, 50.5%, control: n=537, 49.5%), with near-equal proportions of rural and urban participants. Cumulative AEs were identified in 2.3% (95% CI 1.3-4.1) of 2wT participants and 1.0% (95% CI 0.4-2.3) of control participants, demonstrating noninferiority (1-sided 95% CI -0.09 to ∞). Among the 2wT participants, 11 AEs (9 moderate and 2 severe) were identified, compared with 5 AEs (all moderate) among the control participants-a nonsignificant difference in AE rates (P=.13). The 2wT participants attended 0.22 visits, and the control participants attended 1.34 visits-a significant reduction in follow-up visit workload (P<.001). The 2wT approach reduced unnecessary postoperative visits by 84.8%. Daily response rates ranged from 86% on day 3 to 74% on day 13. Among the 2wT participants, 94% (514/547) responded to ≥1 daily SMS text messages over 13 days. CONCLUSIONS: Across rural and urban contexts in South Africa, 2wT was noninferior to routine in-person visits for AE ascertainment, demonstrating 2wT safety. The 2wT approach also significantly reduced the follow-up visit workload, improving efficiency. These results strongly suggest that 2wT provides quality VMMC follow-up and should be adopted at scale. Adaptation of the 2wT telehealth approach to other acute follow-up care contexts could extend these gains beyond VMMC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327271; https://www.clinicaltrials.gov/ct2/show/NCT04327271.

A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines.

Gene expression levels can be an important link DNA between variation and phenotypic manifestations. Our previous map of global gene expression, based on ~400K single nucleotide polymorphisms (SNPs) and 50K transcripts in 400 sib pairs from the MRCA family panel, has been widely used to interpret the results of genome-wide association studies (GWASs). Here, we more than double the size of our initial data set with expression data on 550 additional individuals from the MRCE family panel using the Illumina whole-genome expression array. We have used new statistical methods for dimension reduction to account for nongenetic effects in estimates of expression levels, and we have also included SNPs imputed from the 1000 Genomes Project. Our methods reduced false-discovery rates and increased the number of expression quantitative trait loci (eQTLs) mapped either locally or at a distance (i.e., in cis or trans) from 1534 in the MRCA data set to 4452 (with <5% FDR). Imputation of 1000 Genomes SNPs further increased the number of eQTLs to 7302. Using the same methods and imputed SNPs in the newly acquired MRCE data set, we identified eQTLs for 9000 genes. The combined results identify strong local and distant effects for transcripts from 14,177 genes. Our eQTL database based on these results is freely available to help define the function of disease-associated variants.

Do patients' information requirements for choice in health care vary with their socio-demographic characteristics?

OBJECTIVES: This study examines whether the information used to inform hospital choice, and the sources of that information, varies with patients' socio-demographic characteristics. It also examines whether information used by patients to inform choice is associated with attending their local hospital. METHODS: A survey of 1033 patients who were offered a choice of hospital provider for elective treatment in England. Logistic regression was used to examine associations between patient characteristics and information used to inform choice of a hospital provider and sources of information used. RESULTS: Factors most important to patients in choosing a hospital were quality of care, cleanliness, standard of facilities and reputation. While quality of care and related factors are important to the majority of patients, those with lower levels of education were more likely to report that location and appointment times were important. Those who thought quality important were more likely to attend their local hospital provider. The main sources of information used to inform choice of hospital were own experience, family and friends and the general practitioner (GP). Patients who sought advice from their GP or booking advisors were less likely to attend their local hospitals. CONCLUSIONS: Differences among patients as to what factors are important when choosing a hospital provider and what information and support they access suggest there needs to be a variety of information sources and support available to promote choice. Greater shared decision making through active involvement and support by GPs or booking advisors may be required if they are to make choices in line with their preferences.

Exploring ankylosing spondylitis-associated ERAP1, IL23R and IL12B gene polymorphisms in subphenotypes of psoriatic arthritis.

OBJECTIVE: To ascertain whether AS-associated polymorphisms of ERAP1, IL23R and IL12B genes associate with subphenotypes of PsA, particularly axial radiographic disease once stratified by HLA-B27 and HLA-Cw*0602 status. METHODS: rs30187 (ERAP1 gene), rs6887695 (IL12B gene), rs11209026 and rs7530511 (IL23R gene) single nucleotide polymorphisms were genotyped in 263 PsA cases from a prospective cohort and compared with data from healthy controls (n = 3266-5422). ERAP1 results were stratified according to HLA-B27 and HLA-Cw*0602 status. Investigation of association with age at onset of psoriasis/PsA, arthritic joint count, axial radiographic disease, peripheral radiographic erosions, Psoriasis Area Severity Index, nail score and HAQ was made. RESULTS: There was a strong association between rs6887595 (IL12B) and PsA, with homozygosity for the major allele being more frequent in PsA than controls (odds ratio 1.70; 95% CI 1.3, 2.2; P < 0.001). A trend was demonstrated for the minor allele of rs11209026 (IL23R) to be less frequent in patients with erosive joint disease than in those without erosions or controls (7%, 14% and 12%, respectively). None of the polymorphisms associated with the presence of axial radiographic disease or other clinical parameters. CONCLUSION: We have confirmed a strong association between rs6887595 (IL12B) and PsA. A trend has been demonstrated between an IL23R variant and peripheral erosive disease. ERAP1 was not associated with axial radiographic disease in PsA. Spinal involvement in PsA may be genetically different from that in AS, which is in keeping with previous observations that the clinical and radiographic pattern of axial disease also differs.

Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.

Asthma is caused by a combination of poorly understood genetic and environmental factors. We have systematically mapped the effects of single nucleotide polymorphisms (SNPs) on the presence of childhood onset asthma by genome-wide association. We characterized more than 317,000 SNPs in DNA from 994 patients with childhood onset asthma and 1,243 non-asthmatics, using family and case-referent panels. Here we show multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P value of P < 10(-12). In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P < 10(-22)) in cis with transcript levels of ORMDL3, a member of a gene family that encodes transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.

Integrating pathway analysis and genetics of gene expression for genome-wide association study of basal cell carcinoma.

Genome-wide association studies (GWASs) have primarily focused on marginal effects for individual markers and have incorporated external functional information only after identifying robust statistical associations. We applied a new approach combining the genetics of gene expression and functional classification of genes to the GWAS of basal cell carcinoma (BCC) to identify potential biological pathways associated with BCC. We first identified 322,324 expression-associated single-nucleotide polymorphisms (eSNPs) from two existing GWASs of global gene expression in lymphoblastoid cell lines (n = 955), and evaluated the association of these functionally annotated SNPs with BCC among 2,045 BCC cases and 6,013 controls in Caucasians. We then grouped them into 99 KEGG pathways for pathway analysis and identified two pathways associated with BCC with p value <0.05 and false discovery rate (FDR) <0.5: the autoimmune thyroid disease pathway (mainly HLA class I and II antigens, p < 0.001, FDR = 0.24) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway (p = 0.02, FDR = 0.49). Seventy-nine (25.7%) out of 307 significant eSNPs in the JAK-STAT pathway were associated with BCC risk (p < 0.05) in an independent replication set of 278 BCC cases and 1,262 controls. In addition, the association of JAK-STAT signaling pathway was marginally validated using 16,691 eSNPs identified from 110 normal skin samples (p = 0.08). Based on the evidence of biological functions of the JAK-STAT pathway on oncogenesis, it is plausible that this pathway is involved in BCC pathogenesis.

Does general practice reduce health inequalities? Analysis of quality and outcomes framework data.

BACKGROUND: The government set a series of targets to reduce health inequalities in England by 2010. Primary care has an important role in reducing health inequalities. The aim of the study was to assess the impact of general practice on reducing area-based health inequalities. METHODS: Analysis of differences in achievement on clinical indicators between practices in Spearhead and non-Spearhead Primary Care Trusts (PCTs) using data from the Quality and Outcomes Framework (QOF) for 2004/05 and 2005/06, practice characteristics and Spearhead status of PCTs. The study used data on 8339 primary care practices in England. Unweighted mean reported achievement on subset of 26 clinical indicators was calculated. The study analysed differences in achievement by Spearhead status and deprivation in both years and the change between years. Multiple regression analysis of relationship between Spearhead status, income deprivation, reported achievement and other factors also were carried out. RESULTS: Practices in Spearhead PCTs performed worse than practices in non-Spearhead PCTs in both years but showed greater improvement. Among the most deprived practices, there were no differences in QOF achievement between Spearhead and non-Spearhead PCTs. Previous year's achievement was the strongest predictor of performance. CONCLUSION: The narrowing in performance between practices in Spearhead and non-Spearhead PCTs may have indirectly contributed to a reduction in area-based health inequalities but the differences are small. The lack of difference between the most deprived practices in Spearhead and non-Spearhead PCTs suggest that area-based initiatives to tackle inequalities have not yet had an observable impact on deprived practices. Unobserved factors explain most of the variation in achievement.

Allele-specific transcription of the asthma-associated PHD finger protein 11 gene (PHF11) modulated by octamer-binding transcription factor 1 (Oct-1).

BACKGROUND: Asthma is a common, chronic inflammatory airway disease of major public health importance with multiple genetic determinants. Previously, we found by positional cloning that PHD finger protein 11 (PHF11) on chromosome 13q14 modifies serum immunoglobulin E (IgE) concentrations and asthma susceptibility. No coding variants in PHF11 were identified. OBJECTIVE: Here we investigate the 3 single nucleotide polymorphisms (SNPs) in this gene most significantly associated with total serum IgE levels--rs3765526, rs9526569, and rs1046295--for a role in transcription factor binding. METHODS: We used electrophoretic mobility shift assays to examine the effect of the 3 SNPs on transcription factor binding in 3 cell lines relevant to asthma pathogenesis. Relative preferential expression of alleles was investigated by using the allelotyping method. RESULTS: Electrophoretic mobility shift assays show that rs1046295 modulates allele-specific binding by the octamer-binding transcription factor 1 (Oct-1). Analysis of the relative expression levels of the 2 alleles of this SNP in heterozygous individuals showed a modest, but highly significant (P = 6.5 × 10(-16)), preferential expression of the A allele consistent with a functional role for rs1046295. CONCLUSION: These results suggest a mechanism by which rs1046295 may act as a regulatory variant modulating transcription at this locus and altering asthma susceptibility.

Why we need to face up to the ageing population?

Dr Anna Dixon, Chief Executive at the Centre for Ageing Better, examines the issues around an ageing population, how we have reached this stage and offers potential solutions to the problems it presents. Her book, The Age of Ageing Better? turns the misleading and depressing narrative of burden and massive extra cost of people living longer on its head and shows how our society could thrive if we started thinking differently. She presents a refreshingly optimistic vision for the future that could change the way we value later life in every sense.

Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(-6) and 10(-9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(-7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 x 10(-4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4.

A review of the public health impact of the Quality and Outcomes Framework.

There are clear policy objectives in England to encourage primary care and general practice to address health inequalities. In this paper we explore the potential impact of the Quality and Outcomes Framework (QOF) on health inequalities and review the available evidence including analysis of the area based differences in performance between practices in Spearhead and non-Spearhead areas. Overall, the evidence suggests that differences in performance, as measured by the QOF, between practices in deprived and non-deprived areas are narrowing. Although QOF achievement improved in all practices there is weak evidence as to the impact of the QOF on health. The evidence is equivocal as to whether improvements in clinical care and the narrowing gap in performance are influenced by the incentives created by the QOF or whether this translates into reduced health inequalities. Even though the QOF is only part of the range of incentives which affects practices, it is vital that indicators are aligned to the objective of reducing health inequalities. Additional research is needed to understand whether the QOF ensures that those who are the most difficult to reach and those whose need of care is greatest are getting access to high quality primary care and whether in turn it will succeed in reducing health inequalities.

Could local integration of health and social care finally overcome the pull to the centre?

There are several advantages of Bevan's design, such as progressive funding through taxation and equity of access regardless of income, that we must not lose sight of as we celebrate the NHS's (National Health Service) 70th birthday. However, there remain historical fault-lines dividing health and social care. The challenge is how to preserve equity if a more radical reform were implemented to fully integrate both the funding and delivery of health and social care. Funding from national taxation with defined entitlements could preserve both equity in funding and geographical equity. This does not solve the issue of the pull to the centre, which has been a feature of the NHS throughout its history, according to Klein. This will require a fundamental shift in the use of data. Data must be wrenched from the hands of the regulators and put back in the hands of those who generate them for the purposes of improvement.

Patient choice in general practice: the implications of patient satisfaction surveys.

OBJECTIVES: To identify factors that explain patient satisfaction with general practice physicians and hence that may drive patients' choice of practice. METHODS: Logistic regression analysis of English National Health Service national patient survey data is used to identify the aspects of general practice care that are associated with high levels of overall satisfaction among patients. RESULTS: Confidence and trust in the doctor is the most important factor in explaining the variation in overall patient satisfaction (predicting 82% of satisfaction levels accurately). The seven variables relating to the relationship between patient and doctor have stronger explanatory power than other aspects of the general practitioner (GP) experience. The variables with the lowest overall predictive power are whether the patient was told how long they would have to wait in the surgery (72%), the length of time they had to wait after their appointment time (74%) and ability to get through to the surgery on the phone (74%). CONCLUSIONS: Patients value the quality of their relationship with their doctor more than the appearance of the surgery, accessibility of appointments and their experience in the waiting room. This suggests that, if current restrictions on choice of GP were removed, we would in theory expect a patient's choice to be driven by the quality of the doctor-patient relationship. Once a patient establishes a good relationship with a GP, however, we might expect them to be loyal and therefore unlikely to change practice unless the relationship with the doctor breaks down. Although relationship factors are important to the satisfaction of patients, it is not clear that they will lead large numbers of people to change their GP.

Hardware Implementation of an Adaptive Data Acquisition System for Real-World EEG.

Collecting EEG involves digitizing a very small signal across a vast potential dynamic range, particularly within real-world neuroimaging conditions, where noise can be especially prominent. Conventional methods require highresolution, power-hungry data acquisition systems (DAQs), creating limits on usable time before manual interaction is necessary for recharge. Here, we discuss continued work on an alternative DAQ approach capable of acquiring high resolution data with ultra-low power use by adjusting parameters of the analog front end (AFE) in real time to allow use of low-resolution ADCs. This work compares signal quality of a hardware implementation of our adaptive AFE DAQ to that of an industry standard DAQ. Results demonstrate successful reconstruction of signals in both clean and noisy EEG monitoring environments at low bit-depths while maintaining high correlation and low standard deviation of error. This suggests promise for a fully integrated implementation with substantially lower power consumption.

Consumer competencies and the use of comparative quality information: it isn't just about literacy.

While consumers are increasingly expected to use complex health care information to make informed decisions, it is unclear how many have the skills to do so. In this investigation we examine health literacy, numeracy, and patient activation, assessing the contribution of each to the comprehension of comparative health care performance reports and their use in making an informed choice. A convenience sample of 303 employed-age adults participated in the study. The findings indicate that numeracy skill is the strongest predictor of comprehension, followed by health literacy. Higher activation helps those low in literacy and numeracy compensate for their lower skills and achieve higher levels of comprehension. In addition, making good choices, when trade-offs are necessary, is related to activation separate from comprehension. This is important as many real-life choices involve trade-offs. Results indicate that choice is not just about literacy or comprehension, it also has to do with activation.

Less is more in presenting quality information to consumers.

Much effort has been put into improving measures of health care quality. Although early research suggested that consumers made little use of quality reports, most reports were based on nonstandardized measures and were not user friendly. Information presentation approaches, however, will have a significant influence on what information is attended and used. The present research examines whether information presentation methods differentially influence consumers who differ in numeric skills. Results of three studies support the idea that "less is more" when presenting consumers with comparative performance information to make hospital choices. Results were particularly strong for those lower in numeracy, who had higher comprehension and made better choices when the information-presentation format was designed to ease the cognitive burden and highlight the meaning of important information. These findings have important implications for the sponsors of comparative quality reports designed to inform consumer decision making in health care.

Is the British National Health Service equitable? The evidence on socioeconomic differences in utilization.

Is the British National Health Service (NHS) equitable? This paper considers one part of the answer to this: the utilization of the NHS by different socioeconomic groups (SEGs). It reviews recent evidence from studies on NHS utilization as a whole based on household surveys (macro-studies) and from studies of the utilization of particular services in particular areas (micro-studies). The principal conclusion from the majority of these studies is that, while the distribution of use of general practitioners (GPs) is broadly equitable, that for specialist treatment is pro-rich. Recent micro-studies of cardiac surgery, elective surgery, cancer care, preventive care and chronic care support the findings of an earlier review that use of services was higher relative to need among higher SEGs.