Supporting patients to prepare for total knee replacement: Evidence-, theory- and person-based development of a 'Virtual Knee School' digital intervention.

INTRODUCTION: Digital delivery of pre-operative total knee replacement (TKR) education and prehabilitation could improve patient outcomes pre- and post-operatively. Rigorously developing digital interventions is vital to help ensure they achieve their intended outcomes whilst mitigating their potential drawbacks. OBJECTIVE: To develop a pre-operative TKR education and prehabilitation digital intervention, the 'Virtual Knee School' (VKS). METHODS: The VKS was developed using an evidence-, theory- and person-based approach. This involved a mixed methods design with four phases. The first three focused on planning the VKS. The final phase involved creating a VKS prototype and iteratively refining it through concurrent think-aloud interviews with nine patients who were awaiting/had undergone TKR. Meta-inferences were generated by integrating findings from all the phases. ISRCTN registration of the overall project was obtained on 24 April 2020 (ISRCTN11759773). RESULTS: Most participants found the VKS prototype acceptable overall and considered it a valuable resource. Conversely, a minority of participants felt the prototype's digital format or content did not meet their individual needs. Participants' feedback was used to refine the prototype's information architecture, design and content. Two meta-inferences were generated and recommend: 1. Comprehensive pre-operative TKR education and prehabilitation support should be rapidly accessible in digital and non-digital formats. 2. Pre-operative TKR digital interventions should employ computer- and self-tailoring to account for patients' individual needs and preferences. CONCLUSIONS: Integrating evidence, theory and stakeholders' perspectives enabled the development of a promising VKS digital intervention for patients awaiting TKR. The findings suggest future research evaluating the VKS is warranted and provide recommendations for optimising pre-operative TKR care. PATIENT OR PUBLIC CONTRIBUTION: Patient and Public Involvement (PPI) was central throughout the project. For example, PPI representatives contributed to the project planning, were valued members of the Project Advisory Group, had key roles in developing the VKS prototype and helped disseminate the project findings.

Separation of influenza virus-like particles from baculovirus by polymer-grafted anion exchanger.

The baculovirus expression vector system is a very powerful tool to produce virus-like particles and gene-therapy vectors, but the removal of coexpressed baculovirus has been a major barrier for wider industrial use. We used chimeric human immunodeficiency virus-1 (HIV-1) gag influenza-hemagglutin virus-like particles produced in Tnms42 insect cells using the baculovirus insect cell expression vector system as model virus-like particles. A fast and simple purification method for these virus-like particles with direct capture and purification within one chromatography step was developed. The insect cell culture supernatant was treated with endonuclease and filtered, before it was directly loaded onto a polymer-grafted anion exchanger and eluted by a linear salt gradient. A 4.3 log clearance of baculovirus from virus-like particles was achieved. The absence of the baculovirus capsid protein (vp39) in the product fraction was additionally shown by high performance liquid chromatography-mass spectrometry. When considering a vaccination dose of 109 particles, 4200 doses can be purified per L pretreated supernatant, meeting the requirements for vaccines with <10 ng double-stranded DNA per dose and 3.4 µg protein per dose in a single step. The process is simple with a very low number of handling steps and has the characteristics to become a platform for purification of these types of virus-like particles.

An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial.

BACKGROUND: Handwashing to prevent transmission of respiratory tract infections (RTIs) has been widely advocated, especially during the H1N1 pandemic. However, the role of handwashing is debated, and no good randomised evidence exists among adults in non-deprived settings. We aimed to assess whether an internet-delivered intervention to modify handwashing would reduce the number of RTIs among adults and their household members. METHODS: We recruited individuals sharing a household by mailed invitation through general practices in England. After consent, participants were randomised online by an automated computer-generated random number programme to receive either no access or access to a bespoke automated web-based intervention that maximised handwashing intention, monitored handwashing behaviour, provided tailored feedback, reinforced helpful attitudes and norms, and addressed negative beliefs. We enrolled participants into an additional cohort (randomised to receive intervention or no intervention) to assess whether the baseline questionnaire on handwashing would affect handwashing behaviour. Participants were not masked to intervention allocation, but statistical analysis commands were constructed masked to group. The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of randomly assigned participants who completed follow-up at 16 weeks. This trial is registered with the ISRCTN registry, number ISRCTN75058295. FINDINGS: Across three winters between Jan 17, 2011, and March 31, 2013, we enrolled 20,066 participants and randomly assigned them to receive intervention (n=10,040) or no intervention (n=10,026). 16,908 (84%) participants were followed up with the 16 week questionnaire (8241 index participants in intervention group and 8667 in control group). After 16 weeks, 4242 individuals (51%) in the intervention group reported one or more episodes of RTI compared with 5135 (59%) in the control group (multivariate risk ratio 0·86, 95% CI 0·83-0·89; p<0·0001). The intervention reduced transmission of RTIs (reported within 1 week of another household member) both to and from the index person. We noted a slight increase in minor self-reported skin irritation (231 [4%] of 5429 in intervention group vs 79 [1%] of 6087 in control group) and no reported serious adverse events. INTERPRETATION: In non-pandemic years, an effective internet intervention designed to increase handwashing could have an important effect in reduction of infection transmission. In view of the heightened concern during a pandemic and the likely role of the internet in access to advice, the intervention also has potential for effective implementation during a pandemic. FUNDING: Medical Research Council.

Understanding usage of a hybrid website and smartphone app for weight management: a mixed-methods study.

BACKGROUND: Advancements in mobile phone technology offer huge potential for enhancing the timely delivery of health behavior change interventions. The development of smartphone-based health interventions (apps) is a rapidly growing field of research, yet there have been few longitudinal examinations of how people experience and use these apps within their day-to-day routines, particularly within the context of a hybrid Web- and app-based intervention. OBJECTIVE: This study used an in-depth mixed-methods design to examine individual variation in (1) impact on self-reported goal engagement (ie, motivation, self-efficacy, awareness, effort, achievement) of access to a weight management app (POWeR Tracker) when provided alongside a Web-based weight management intervention (POWeR) and (2) usage and views of POWeR Tracker. METHODS: Thirteen adults were provided access to POWeR and were monitored over a 4-week period. Access to POWeR Tracker was provided in 2 alternate weeks (ie, weeks 1 and 3 or weeks 2 and 4). Participants' goal engagement was measured daily via self-report. Mixed effects models were used to examine change in goal engagement between the weeks when POWeR Tracker was and was not available and whether the extent of change in goal engagement varied between individual participants. Usage of POWeR and POWeR Tracker was automatically recorded for each participant. Telephone interviews were conducted and analyzed using inductive thematic analysis to further explore participants' experiences using POWeR and POWeR Tracker. RESULTS: Access to POWeR Tracker was associated with a significant increase in participants' awareness of their eating (ß1=0.31, P=.04) and physical activity goals (ß1=0.28, P=.03). The level of increase varied between individual participants. Usage data showed that participants used the POWeR website for similar amounts of time during the weeks when POWeR Tracker was (mean 29 minutes, SD 31 minutes) and was not available (mean 27 minutes, SD 33 minutes). POWeR Tracker was mostly accessed in short bursts (mean 3 minutes, SD 2 minutes) during convenient moments or moments when participants deemed the intervention content most relevant. The qualitative data indicated that nearly all participants agreed that it was more convenient to access information on-the-go via their mobiles compared to a computer. However, participants varied in their views and usage of the Web- versus app-based components and the informational versus tracking tools provided by POWeR Tracker. CONCLUSIONS: This study provides evidence that smartphones have the potential to improve individuals' engagement with their health-related goals when used as a supplement to an existing online intervention. The perceived convenience of mobile access to information does not appear to deter use of Web-based interventions or strengthen the impact of app access on goal engagement. A mixed-methods design enabled exploration of individual variation in daily usage of the app-based tools.

Greater maltreatment severity is associated with smaller brain volume with implication for intellectual ability in young children.

Background: Childhood maltreatment profoundly alters trajectories of brain development, promoting markedly increased long-term health risks and impaired intellectual development. However, the immediate impact of maltreatment on brain development in children and the extent to which altered global brain volume contributes to intellectual development in children with maltreatment experience is currently unknown. We here utilized MRI data obtained from children within 6 months after the exposure to maltreatment to assess the association of maltreatment severity with global brain volume changes. We further assessed the association between maltreatment severity and intellectual development and tested for the mediating effect of brain volume on this association. Method: We used structural MRI (3T) in a sample of 49 children aged 3-5 years with maltreatment exposure, i.e. emotional and physical abuse and/or neglect within 6 months, to characterize intracranial and tissue-specific volumes. Maltreatment severity was coded using the Maternal Interview for the Classification of Maltreatment. IQ was tested at study entry and after one year using the Snijders Oomen Nonverbal Test. Results: Higher maltreatment severity was significantly correlated with smaller intracranial volume (r = -.393, p = .008), which was mainly driven by lower total brain volume (r = -.393, p = .008), which in turn was primarily due to smaller gray matter volume (r = -.454, p = .002). Furthermore, smaller gray matter volume was associated with lower IQ at study entry (r = -.548, p < .001) and predicted IQ one year later (r = -.493, p = .004.). The observed associations were independent of potential confounding variables, including height, socioeconomic status, age and sex. Importance: We provide evidence that greater maltreatment severity in early childhood is related to smaller brain size at a very young age with significant consequences for intellectual ability, likely setting a path for far-reaching long-term disadvantages. Insights into the molecular and neural processes that underlie the impact of maltreatment on brain structure and function are urgently needed to derive mechanism-driven targets for early intervention.

A randomised controlled trial of a digital intervention (Renewed) to support symptom management, wellbeing and quality of life in cancer survivors.

BACKGROUND: Many cancer survivors following primary treatment have prolonged poor quality of life. AIM: To determine the effectiveness of a bespoke digital intervention to support cancer survivors. DESIGN: Pragmatic parallel open randomised trial. SETTING: UK general practices. METHODS: People having finished primary treatment (<= 10 years previously) for colo-rectal, breast or prostate cancers, with European-Organization-for-Research-and-Treatment-of-Cancer QLQ-C30 score <85, were randomised by online software to: 1)detailed 'generic' digital NHS support ('LiveWell';n=906), 2) a bespoke complex digital intervention ('Renewed';n=903) addressing symptom management, physical activity, diet, weight loss, distress, or 3) 'Renewed-with-support' (n=903): 'Renewed' with additional brief email and telephone support. RESULTS: Mixed linear regression provided estimates of the differences between each intervention group and generic advice: at 6 months (primary time point: n's respectively 806;749;705) all groups improved, with no significant between-group differences for EORTC QLQ-C30, but global health improved more in both intervention groups. By 12 months there were: small improvements in EORTC QLQ-C30 for Renewed-with-support (versus generic advice: 1.42, 95% CIs 0.33-2.51); both groups improved global health (12 months: renewed: 3.06, 1.39-4.74; renewed-with-support: 2.78, 1.08-4.48), dyspnoea, constipation, and enablement, and lower NHS costs (generic advice £265: in comparison respectively £141 (153-128) and £77 (90-65) lower); and for Renewed-with-support improvement in several other symptom subscales. No harms were identified. CONCLUSION: Cancer survivors quality of life improved with detailed generic online support. Robustly developed bespoke digital support provides limited additional short term benefit, but additional longer term improvement in global health enablement and symptom management, with substantially lower NHS costs.

Osteogenesis Imperfecta and hearing loss in the paediatric population.

BACKGROUND: Osteogenesis Imperfecta is a genetic disorder affecting the synthesis of collagen in the body. It is also known as 'Brittle Bone Disease'. It is heterogenous in its clinical presentation. The commonest presentation is a history of frequent fractures, joint deformities and blue sclera. Secondary deformities of the extremities, spine, skull as well short stature observed frequently. Hearing loss has been well documented to occur in Osteogenesis Imperfecta. It is most commonly seen in types I, II and III. Hearing loss forms part of the diagnostic criteria for these types. Depending on the study, the prevalence of hearing loss in children with Osteogenesis imperfecta is between 6.7% and 77.3% The estimated prevalence of Osteogenesis Imperfecta is 1 in 20000. OBJECTIVES: In South Africa, the commonest type of Osteogenesis Imperfecta was found to be Type III. The prevalence of OI Type III has been estimated to be between 1:125000 and 1:200000. Hearing loss is a common feature of OI Type III. METHODS: This study was a Prospective Cross-sectional study. Ethics Approval was obtained from the University of Witwatersrand Ethics committee (Ethics number M190975) Children with Osteogenesis Imperfecta attending the Metabolic Bone Clinic at Chris Hani Baragwanath Academic Hospital were the target group. The patients and their parents or guardians were recruited at the clinic after a consent and or an assent was obtained. An Otoscopy followed by tympanometry and a hearing screen based on the age of the patient was done. DPEOAEs were also done as a screening test to confirm the pure tone audiogram findings. The results were given to the patients and their parents/guardians immediately. RESULTS: The paediatric patients with Osteogenesis Imperfecta who consented to take part in the study had their hearing screen done at the Audiology Department at Chris Hani Baragwanath Academic Hospital. All of the children were found to have normal hearing. On tympanometry, all except 2 were found to have type A curves in bilaterally. Two patients had a type As curve in one ear with an A curve on the other side. CONCLUSION: Hearing loss in Osteogenesis Imperfecta forms part of the diagnostic criteria for certain types of this genetic disorder. Hearing loss in the paediatric patients does not seem to be as prevalent as previously thought. All the patients involved in the study were receiving the bisphosphonate therapy (Zoledronic acid) for OI. This may possibly cause a delay in the onset of hearing loss but long term follow-up studies and bigger sample sizes will be required to prove this hypothesis.

Using the internet to promote health behavior change: a systematic review and meta-analysis of the impact of theoretical basis, use of behavior change techniques, and mode of delivery on efficacy.

BACKGROUND: The Internet is increasingly used as a medium for the delivery of interventions designed to promote health behavior change. However, reviews of these interventions to date have not systematically identified intervention characteristics and linked these to effectiveness. OBJECTIVES: The present review sought to capitalize on recently published coding frames for assessing use of theory and behavior change techniques to investigate which characteristics of Internet-based interventions best promote health behavior change. In addition, we wanted to develop a novel coding scheme for assessing mode of delivery in Internet-based interventions and also to link different modes to effect sizes. METHODS: We conducted a computerized search of the databases indexed by ISI Web of Knowledge (including BIOSIS Previews and Medline) between 2000 and 2008. Studies were included if (1) the primary components of the intervention were delivered via the Internet, (2) participants were randomly assigned to conditions, and (3) a measure of behavior related to health was taken after the intervention. RESULTS: We found 85 studies that satisfied the inclusion criteria, providing a total sample size of 43,236 participants. On average, interventions had a statistically small but significant effect on health-related behavior (d(+) = 0.16, 95% CI 0.09 to 0.23). More extensive use of theory was associated with increases in effect size (P = .049), and, in particular, interventions based on the theory of planned behavior tended to have substantial effects on behavior (d(+) = 0.36, 95% CI 0.15 to 0.56). Interventions that incorporated more behavior change techniques also tended to have larger effects compared to interventions that incorporated fewer techniques (P < .001). Finally, the effectiveness of Internet-based interventions was enhanced by the use of additional methods of communicating with participants, especially the use of short message service (SMS), or text, messages. CONCLUSIONS: The review provides a framework for the development of a science of Internet-based interventions, and our findings provide a rationale for investing in more intensive theory-based interventions that incorporate multiple behavior change techniques and modes of delivery.

Evaluation of a Web-based intervention providing tailored advice for self-management of minor respiratory symptoms: exploratory randomized controlled trial.

BACKGROUND: There has been relatively little research on the role of web-based support for self-care in the management of minor, acute symptoms, in contrast to the wealth of recent research into Internet interventions to support self-management of long-term conditions. OBJECTIVE: This study was designed as an evaluation of the usage and effects of the "Internet Doctor" website providing tailored advice on self-management of minor respiratory symptoms (eg, cough, sore throat, fever, runny nose), in preparation for a definitive trial of clinical effectiveness. The first aim was to evaluate the effects of using the Internet Doctor webpages on patient enablement and use of health services, to test whether the tailored, theory-based advice provided by the Internet Doctor was superior to providing a static webpage providing the best existing patient information (the control condition). The second aim was to gain an understanding of the processes that might mediate any change in intentions to consult the doctor, by comparing changes in relevant beliefs and illness perceptions in the intervention and control groups, and by analyzing usage of the Internet Doctor webpages and predictors of intention change. METHODS: Participants (N = 714) completed baseline measures of beliefs about their symptoms and self-care online, and were then automatically randomized to the Internet Doctor or control group. These measures were completed again by 332 participants after 48 hours. Four weeks later, 214 participants completed measures of enablement and health service use. RESULTS: The Internet Doctor resulted in higher levels of satisfaction than the control information (mean 6.58 and 5.86, respectively; P = .002) and resulted in higher levels of enablement a month later (median 3 and 2, respectively; P = .03). Understanding of illness improved in the 48 hours following use of the Internet Doctor webpages, whereas it did not improve in the control group (mean change from baseline 0.21 and -0.06, respectively, P = .05). Decline in intentions to consult the doctor between baseline and follow-up was predicted by age (beta = .10, P= .003), believing before accessing the website that consultation was necessary for recovery (beta = .19, P < .001), poor understanding of illness (beta = .11, P = .004), emotional reactions to illness (beta = .15, P <.001), and use of the Diagnostic section of the Internet Doctor website (beta = .09, P = .007). CONCLUSIONS: Our findings provide initial evidence that tailored web-based advice could help patients self-manage minor symptoms to a greater extent. These findings constitute a sound foundation and rationale for future research. In particular, our study provides the evidence required to justify carrying out much larger trials in representative population samples comparing tailored web-based advice with routine care, to obtain a definitive evaluation of the impact on self-management and health service use.

Understanding reactions to an internet-delivered health-care intervention: accommodating user preferences for information provision.

BACKGROUND: It is recognised as good practice to use qualitative methods to elicit users' views of internet-delivered health-care interventions during their development. This paper seeks to illustrate the advantages of combining usability testing with 'theoretical modelling', i.e. analyses that relate the findings of qualitative studies during intervention development to social science theory, in order to gain deeper insights into the reasons and context for how people respond to the intervention. This paper illustrates how usability testing may be enriched by theoretical modelling by means of two qualitative studies of users' views of the delivery of information in an internet-delivered intervention to help users decide whether they needed to seek medical care for their cold or flu symptoms. METHODS: In Study 1, 21 participants recruited from a city in southern England were asked to 'think aloud' while viewing draft web-pages presented in paper format. In Study 2, views of our prototype website were elicited, again using think aloud methods, in a sample of 26 participants purposively sampled for diversity in education levels. Both data-sets were analysed by thematic analysis. RESULTS: Study 1 revealed that although the information provided by the draft web-pages had many of the intended empowering benefits, users often felt overwhelmed by the quantity of information. Relating these findings to theory and research on factors influencing preferences for information-seeking we hypothesised that to meet the needs of different users (especially those with lower literacy levels) our website should be designed to provide only essential personalised advice, but with options to access further information. Study 2 showed that our website design did prove accessible to users with different literacy levels. However, some users seemed to want still greater control over how information was accessed. CONCLUSIONS: Educational level need not be an insuperable barrier to appreciating web-based access to detailed health-related information, provided that users feel they can quickly gain access to the specific information they seek.

Motion sickness: effect of the magnitude of roll and pitch oscillation.

BACKGROUND: Rotational oscillation in roll and pitch can cause motion sickness, but it is not known how sickness depends on the magnitude of rotational oscillation or whether there is a difference between the two axes of motion. HYPOTHESIS: It was hypothesized that motion sickness would increase similarly with increasing magnitudes of roll and pitch oscillation. METHOD: There were 120 subjects (6 groups of 20 subjects) who were exposed to 30 min of 0.2-Hz sinusoidal roll or pitch oscillation at 1 of 3 magnitudes: 1) +/- 1.830; 2) +/- 3.66 degrees; or 3) +/- 7.32 degrees. Subjects sitting in a closed cabin with their eyes open gave ratings of their illness on a 7-point illness rating scale at 1-min intervals. RESULTS: Over the six conditions, mild nausea was reported by 17.5% of subjects. With both roll oscillation and pitch oscillation, mean illness ratings were least with +/- 1.83 degrees of rotational oscillation and greater with +/- 3.66 degrees and +/- 7.32 degrees of oscillation. At none of the three magnitudes of oscillation was there a significant difference in motion sickness caused by roll and pitch oscillation. CONCLUSIONS: With rotational oscillation about an Earth-horizontal axis, there is a trend for motion sickness to increase with increasing motion magnitude. For the conditions investigated, similar motion sickness was caused by roll and pitch oscillation.

Motion sickness: effect of changes in magnitude of combined lateral and roll oscillation.

BACKGROUND: In tilting trains, low-frequency lateral and roll oscillation combine and can cause motion sickness. During a journey, passengers are exposed to motions of varying magnitudes, but the effect of a change in magnitude on motion sickness is not known. It was hypothesized that the rate of increase in motion sickness would be greater during exposure to a high-magnitude motion than during exposure to a low-magnitude motion and that there would be no difference in sickness between motions when the 'motion sickness dose value' was the same. METHOD: At intervals of at least 1 wk, 20 subjects were exposed to 4 conditions consisting of 0.1-Hz sinusoidal lateral oscillation with 50% roll compensation. Each condition had four successive 15-min periods of motion presented without a break (total duration 1 h). Each 15-min motion was either a high-magnitude motion (H) (+/- 1.26 ms(-2) lateral oscillation with +/- 3.66 degrees roll oscillation) or a low-magnitude motion (L) (+/- 0.63 ms(-2) lateral oscillation with +/-1.83 degrees roll oscillation). The four conditions involved four different combinations of magnitude: 1) LLLL, 2) HHHH, 3) LHHL, and 4) HLHL. Subjects were seated in a rigid closed cabin and gave ratings of sickness at 1-min intervals. RESULTS: Symptoms of motion sickness were experienced in 56 of the 80 sessions. The rate of increase in motion sickness was greater with the high-magnitude motion than with the low-magnitude motion. For the two variable conditions (i.e., LHHL and HLHL), there was no significant difference in accumulated illness ratings when the motion sickness dose values were the same (i.e., between 30 and 60 min of motion). Illness ratings decreased during periods of low-magnitude motion experienced after periods of high-magnitude motion and also after the cessation of all motion. CONCLUSIONS: With combined lateral and roll oscillation, the rate of increase in motion sickness is greater during periods of high-magnitude motion than during periods of low-magnitude motion. With motions having the same motion sickness dose value but different sequences of exposure, there were no significant differences in accumulated illness ratings at times when the motion sickness dose values were the same.

Motion sickness from combined lateral and roll oscillation: effect of varying phase relationships.

BACKGROUND: Previous studies have investigated motion sickness caused by combined lateral and roll oscillation occurring in phase with each other. In tilting trains there can be a phase difference between the two motions. HYPOTHESIS: It was hypothesized that sickness caused by combined lateral and roll oscillation would depend on the phase between the lateral acceleration and the roll displacement. METHOD: At intervals of at least 1 wk, 20 subjects were seated in a cabin and exposed to four 30-min exposures of combined 0.2 Hz sinusoidal lateral acceleration (+/- 1.26 ms(-2)) and 0.2 Hz roll displacement (+/- 7.32 degrees). The roll oscillation had one of four phases relative to the lateral oscillation: 1) 0 degrees delay (giving 100% compensation of the lateral acceleration); 2) 14.5 degrees delay (75% compensation); 3) 29 degrees delay (50% compensation); and 4) 29 degrees advance (50% compensation). Subjects gave ratings of sickness at 1-min intervals. RESULTS: Sickness was greatest with no delay (100% compensation). Increasing the delay to 14.5 degrees (75% compensation) and to 29 degrees (50% compensation) decreased sickness. Less sickness occurred when the roll displacement led the lateral acceleration by 29 degrees (phase advance) than when the roll displacement followed the lateral acceleration by 29 degrees (phase delay). CONCLUSIONS: With combined lateral and roll oscillation, sickness depends on the phase between the two motions. Increasing the delay in the roll motion reduces sickness, but also reduces the compensation. There is less sickness when the roll displacement leads the lateral acceleration than when the roll displacement lags the lateral acceleration.

Primary care randomised controlled trial of a tailored interactive website for the self-management of respiratory infections (Internet Doctor).

OBJECTIVE: To assess an internet-delivered intervention providing advice to manage respiratory tract infections (RTIs). DESIGN: Open pragmatic parallel group randomised controlled trial. SETTING: Primary care in UK. PARTICIPANTS: Adults (aged ≥18) registered with general practitioners, recruited by postal invitation. INTERVENTION: Patients were randomised with computer-generated random numbers to access the intervention website (intervention) or not (control). The intervention tailored advice about the diagnosis, natural history, symptom management (particularly paracetamol/ibuprofen use) and when to seek further help. OUTCOMES: Primary: National Health Service (NHS) contacts for those reporting RTIs from monthly online questionnaires for 20 weeks. Secondary: hospitalisations; symptom duration/severity. RESULTS: Results 3044 participants were recruited. 852 in the intervention group and 920 in the control group reported one or more RTIs, among whom there a modest increase in NHS Direct contacts in the intervention group (intervention 44/1734 (2.5%) versus control 24/1842 (1.3%); multivariate Risk Ratio (RR) 2.53 (95% CI 1.10 to 5.82, p=0.029)). Conversely reduced contact with doctors occurred (283/1734 (16.3%) vs 368/1845 (20.0%); risk ratio 0.71, 0.53 to 0.95, p=0.019). Reduction in contacts occurred despite slightly longer illness duration (11.3 days versus 10.9 days respectively; multivariateestimate 0.48 days longer (-0.16 to 1.12, p=0.141) and more days of illness rated moderately bad or worse illness (0.53 days; 0.12 to 0.94, p=0.012). The estimate of slower symptom resolution in the intervention group was attenuated when controlling for whether individuals had used webpages which advocated ibuprofen use (length of illness 0.22 days, −0.51 to 0.95, p=0.551; moderately bad or worse symptoms 0.36 days, −0.08 to 0.80, p=0.105). There was no evidence of increased hospitalisations (risk ratio 0.13; 0.02 to 1.01; p=0.051). CONCLUSIONS: An internet-delivered intervention for the self-management of RTIs modifies help-seeking behaviour, and does not result in more hospital admissions due to delayed help seeking. Advising the use of ibuprofen may not be helpful. TRIAL REGISTRATION NUMBER: ISRCTN91518452.

Review Article: Chiari Type I Malformation with or Without Syringomyelia: Prevalence and Genetics.

Chiari type I malformation has traditionally been defined as a downward herniation of the cerebellar tonsils of ≥5 mm through the foramen magnum and it is likely associated with a volumetrically reduced posterior fossa. Syringomyelia is commonly associated with Chiari type I malformation. We estimate the prevalence of these two conditions and determine that they are more common than previously expected. We identify the genetic syndromes associated with some cases of Chiari type I malformation, and we provide evidence in favor of a genetic hypothesis for at least a subset of the nonsyndromic cases.