Ocular radiation exposure is negligible in normal volume endourological practice.

INTRODUCTION: The annual dose limit for radiation exposure to the eye has been reduced recently; the eye is widely recognised as one of the most radiosensitive tissues in the body. There is minimal good quality research as to the radiation dose that the eye receives during endourological surgery and this study aimed to address this. METHODS: A prospective study was performed over an 8-month period at a single large teaching hospital in the UK. Three index procedures were included: ureteric stent insertion, ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL). Surgeons wore a dosimeter on the glabella with fluoroscopy time (FT) and dose area product (DAP) recorded for each case. RESULTS: A total of 404 procedures were included (247 URSs, 150 ureteric stent insertions and 7 PCNLs). Dosimeters were worn by ten surgeons. Mean FTs (URS 20.56s; ureteric stent 18.96s; PCNL 360.67s) and mean DAP (URS 100.82cGy/m2, ureteric stent 119.82cGy/m2 and PCNL 1121.62cGy/m2) were identified with significant intersurgeon variability. No surgeon had a total dosimeter dose >0.00mSv. CONCLUSIONS: The International Commission on Radiological Protection recently reduced the yearly eye dose limit from 150 to 20mSv. Cataractogenesis is no longer considered a typical deterministic effect, with a threshold level below which no effect occurs. Even in higher volume centres, these annual limits are unlikely to be reached. Lead glasses may be considered for surgeons and radiologists with the highest exposure but, for the majority, ocular radiation exposure is negligible.

Randomized controlled pilot trial with ion-exchange water softeners to prevent eczema (SOFTER trial).

BACKGROUND: Observational studies suggest an increased risk of eczema in children living in hard versus soft water areas, and there is, therefore, an interest in knowing whether softening water may prevent eczema. We evaluated the feasibility of a parallel-group assessor-blinded pilot randomized controlled trial to test whether installing a domestic ion-exchange water softener before birth in hard water areas reduces the risk of eczema in infants with a family history of atopy. METHODS: Pregnant women living in hard water areas (>250 mg/L calcium carbonate) in and around London UK, were randomized 1:1 antenatally to either have an ion-exchange water softener installed in their home or not (ie to continue to receive usual domestic hard water). Infants were assessed at birth and followed up for 6 months. The main end-points were around feasibility, the primary end-point being the proportion of eligible families screened who were willing and able to be randomized. Clinical end-points were evaluated including frequency of parent-reported doctor-diagnosed eczema and visible eczema on skin examination. Descriptive analyses were conducted, and no statistical testing was performed as this was a pilot study. RESULTS: One hundred and forty-nine families screened were eligible antenatally and 28% (41/149) could not have a water softener installed due to technical reasons or lack of landlord approval. Eighty of 149 (54%) were randomized, the primary end-point. Two participants withdrew immediately after randomization, leaving 39 participants in each arm (78 total). Attrition was 15% (12/78) by 6 months postpartum. All respondents (n = 69) to the study acceptability questionnaire reported that the study was acceptable. Fifty-six of 708 (7.9%) water samples in the water softener arm were above the hard water threshold of 20 mg/L CaCO3 . At 6 months of age 27/67 infants (40%) developed visible eczema, 12/36 (33%) vs. 15/31 (48%) in the water softener and control groups, respectively, difference -15% (95% CI -38, 8.3%), with most assessments (≥96%) remaining blinded. Similarly, a lower proportion of infants in the water softener arm had parent-reported, doctor-diagnosed eczema by 6 months compared to the control arm, 6/17 (35%) versus 9/19 (47%), difference -12% (95% CI -44, 20%). CONCLUSION: A randomized controlled trial of water softeners for the prevention of atopic eczema in high-risk infants is feasible and acceptable. TRIAL REGISTRATION: NCT03270566 (clinicaltrials.gov).

Extracellular buffer choice influences acid-base responses and gastrointestinal symptoms.

To compare the bicarbonate kinetics and gastrointestinal (GI) symptom responses between an equal dose of sodium bicarbonate and sodium citrate using delayed-release capsules. Thirteen active males (age 20.5 ± 2.1 y, height 1.8 ± 0.1 m and body mass [BM] 76.5 ± 9.6 kg) consumed either 0.3 g.kg-1 BM sodium bicarbonate, sodium citrate or a placebo, using a double-blind, randomized crossover design. Blood bicarbonate ion (HCO3-) concentration, pH and GI symptoms were measured pre-consumption and every 10 min for 180 min post-consumption. Blood HCO3- concentration (P < 0.001) and pH (P = 0.040) were significantly higher in the sodium bicarbonate condition compared with sodium citrate condition up to 3 h post-consumption. Peak blood HCO3- concentration was significantly higher with the sodium bicarbonate compared with citrate (P < 0.001). Mean GI symptom scores were lower (P = 0.037) for sodium citrate (1.5 ± 1.8 AU) than bicarbonate (2.6 ± 3.1 AU), with considerable inter-individual variability. No GI symptoms were reported following consumption of the placebo. Both substances increase HCO3- values significantly, with sodium bicarbonate causing significantly higher pH and HCO3- values than the same dose of sodium citrate, but results in slightly more severe GI symptoms.

Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiation Therapy Compared With Surgery and Radiofrequency Ablation in Two Patient Cohorts: Metastatic Liver Cancer and Hepatocellular Carcinoma.

AIMS: To compare the cost-effectiveness of stereotactic ablative body radiation therapy (SABR) with radiofrequency ablation and surgery in adult patients with metastatic liver cancer and hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Two patient cohorts were assessed: liver oligometastases and HCC. For each patient cohort, a decision analytic model was constructed to assess the cost-effectiveness of interventions over a 5-year horizon. A Markov process was embedded in the decision model to simulate the possible prognosis of cancer. Data on transition probabilities, survival, side-effects, quality of life and costs were obtained from published sources and the SABR Commissioning through Evaluation (CtE) scheme. The primary outcome was the incremental cost-effectiveness ratio with respect to quality-adjusted life-years. The robustness of the results was examined in a sensitivity analysis. Analyses were conducted from a National Health Service and Personal Social Services perspective. RESULTS: In the base case analysis, which assumed that all three interventions were associated with the same cancer progression rates and mortality rates, SABR was the most cost-effective intervention for both patient cohorts. This conclusion was sensitive to the cancer progression rate, mortality rate and cost of interventions. Assuming a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, the probability that SABR is cost-effective was 57% and 50% in liver oligometastases and HCC, respectively. CONCLUSIONS: Our results indicate a potential for SABR to be cost-effective for patients with liver oligometastases and HCC. This finding supports further investigation in clinical trials directly comparing SABR with surgery and radiofrequency ablation.

An observational study to compare the utilisation of computed tomography colonography with optical colonoscopy as the first diagnostic imaging tool in patients with suspected colorectal cancer.

AIM: To evaluate the clinical and cost implications of using computed tomography colonography (CTC) compared to optical colonoscopy (OC) as the initial colonic investigation in patients with low-to-intermediate risk of colorectal cancer (CRC). MATERIALS AND METHODS: A non-randomised, prospective single-centre study recruited 180 participants to compare the cost implications of two clinical pathways used in the diagnosis of low-to-intermediate risk of CRC that differ in the initial diagnostic test, either CTC or OC. Costs were compared using generalised linear models (GLM) and combined with quality-adjusted life years (QALYs, based on the EQ-5D-5L) to estimate cost-effectiveness at 6 months post-recruitment. Secondary outcomes assessed access to care and patient satisfaction. RESULTS: Mean (SD, n) cost at 6 months post-recruitment per participant was £991 (£316, n=105) for the OC group and £645 (£607, n=68) for the CTC group, leading to an estimated cost difference of -£370 (95% CI: -£554, -£185, p<0.001). Assuming a £20,000 willingness-to-pay per QALY threshold, there was a 91.4% probability of CTC being cost-effective at month 6. The utilisation of CTC led to improved access to care, with a shorter mean time from referral from primary care to results (6.3 days difference, p=0.005). No differences in patient satisfaction were detected between both groups. CONCLUSION: The utilisation of CTC as the first-line investigation for patients with low-to-intermediate risk of CRC has the potential to release OC capacity, of pivotal importance for patients more likely to benefit from an invasive diagnostic approach.

Longitudinal analysis of the effect of water hardness on atopic eczema: evidence for gene-environment interaction.

BACKGROUND: Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life. OBJECTIVES: To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss-of-function variants. METHODS: We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. RESULTS: Of 1303 infants enrolled in the EAT study, 91·3% (n = 1189) attended the final clinic visit and 94·0% (n = 1225) of participants' families completed the 36-month questionnaire. In total, 761 (58·4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L-1 CaCO3 ) vs. softer (≤ 257 mg L-1 CaCO3 ) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92-1·24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI 2·03-3·66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1·80, 95% CI 1·17-2·78) and transepidermal water loss (0·0081 g m-2 h-1 per mg L-1 CaCO3 , 95% CI 0·00028-0·016). CONCLUSIONS: There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE.

RESISTing the Need to Quantify: Putting Qualitative FDG-PET/CT Tumor Response Assessment Criteria into Daily Practice.

Tumor response assessments are essential to evaluate cancer treatment efficacy and prognosticate survival in patients with cancer. Response criteria have evolved over multiple decades, including many imaging modalities and measurement schema. Advances in FDG-PET/CT have led to tumor response criteria that harness the power of metabolic imaging. Qualitative PET/CT assessment schema are easy to apply clinically, are reproducible, and yield good prognostic results. We present 3 such criteria, namely, the Lugano classification for lymphoma, the Hopkins criteria, and the Neck Imaging Reporting and Data Systems criteria for head and neck cancers. When comparing baseline PET/CTs with interim or end-of-treatment PET/CTs, radiologists can classify the tumor response as complete metabolic response, partial metabolic response, no metabolic response, or progressive disease, which has important implications in directing further cancer management and long-term patient prognosis. The purpose of this article is to review the progression of tumor response assessments from CT- and PET/CT-based quantitative and semi-quantitative systems to PET/CT-based qualitative systems; introduce the classification schema for these systems; and describe how to use these rapid, powerful, and qualitative PET/CT-based systems in daily practice through illustrative cases.

Clinical and cost implications of using immediate MRI in the management of patients with a suspected scaphoid fracture and negative radiographs results from the SMaRT trial.

AIMS: The aim of the Scaphoid Magnetic Resonance Imaging in Trauma (SMaRT) trial was to evaluate the clinical and cost implications of using immediate MRI in the acute management of patients with a suspected fracture of the scaphoid with negative radiographs. PATIENTS AND METHODS: Patients who presented to the emergency department (ED) with a suspected fracture of the scaphoid and negative radiographs were randomized to a control group, who did not undergo further imaging in the ED, or an intervention group, who had an MRI of the wrist as an additional test during the initial ED attendance. Most participants were male (52% control, 61% intervention), with a mean age of 36.2 years (18 to 73) in the control group and 38.2 years (20 to 71) in the intervention group. The primary outcome was total cost impact at three months post-recruitment. Secondary outcomes included total costs at six months, the assessment of clinical findings, diagnostic accuracy, and the participants' self-reported level of satisfaction. Differences in cost were estimated using generalized linear models with gamma errors. RESULTS: The mean cost up to three months post-recruitment per participant was £542.40 (sd £855.20, n = 65) for the control group and £368.40 (sd £338.60, n = 67) for the intervention group, leading to an estimated cost difference of £174 (95% confidence interval (CI) -£30 to £378; p = 0.094). The cost difference per participant increased to £266 (95% CI £3.30 to £528; p = 0.047) at six months. Overall, 6.2% of participants (4/65, control group) and 10.4% of participants (7/67, intervention group) had sustained a fracture of the scaphoid (p = 0.37). In addition, 7.7% of participants (5/65, control group) and 22.4% of participants (15/67, intervention group) had other fractures diagnosed (p = 0.019). The use of MRI was associated with higher diagnostic accuracy both in the diagnosis of a fracture of the scaphoid (100.0% vs 93.8%) and of any other fracture (98.5% vs 84.6%). CONCLUSION: The use of immediate MRI in the management of participants with a suspected fracture of the scaphoid and negative radiographs led to cost savings while improving the pathway's diagnostic accuracy and patient satisfaction. Cite this article: Bone Joint J 2019;101-B:984-994.

Epilepsy as a systemic condition: Link with somatic comorbidities.

BACKGROUND: People with epilepsy have more concomitant medical conditions than the general population; these comorbidities play an important role in premature mortality. We sought to generate explanatory hypotheses about the co-occurrence of somatic comorbidities and epilepsy, avoiding causal and treatment-resultant biases. METHODS: We collected clinical, demographic and somatic comorbidity data for 2016 consecutive adults with epilepsy undergoing assessment at a tertiary centre and in 1278 people with epilepsy in the community. Underlying causes of epilepsy were not classed as comorbidities. RESULTS: Somatic comorbidities were more frequent in the referral centre (49%) where people more frequently had active epilepsy than in the community (36%). Consistent risk factors for comorbidities were found in both cohorts. Using multivariable ordinal regression adjusted for age, longer epilepsy duration and an underlying brain lesion were independently associated with a smaller burden of somatic conditions. The treatment burden, measured by the number of drugs to which people were exposed, was not an independent predictor. Shorter epilepsy duration was a predictor for conditions that conceivably harbour significant mortality risks. CONCLUSIONS: Somatic comorbidities do not occur randomly in relation to epilepsy; having more severe epilepsy seems to be a risk factor. Independently from age, the early period after epilepsy onset appears to be at particular risk, although it is not clear whether this relates to an early mortality or to a later decrease in the burden of comorbidities. These results suggest that, for some people, epilepsy should be considered a systemic condition not limited to the CNS.

Randomized clinical trial of comprehensive geriatric assessment and optimization in vascular surgery.

BACKGROUND: Increasing numbers of older patients are undergoing vascular surgery. Inadequate preoperative assessment and optimization may contribute to increased postoperative morbidity and mortality. METHODS: Patients aged at least 65 years scheduled for elective aortic aneurysm repair or lower-limb arterial surgery were enrolled in an RCT of standard preoperative assessment or preoperative comprehensive geriatric assessment and optimization. Randomization was stratified by sex and surgical site (aorta/lower limb). Primary outcome was length of hospital stay. Secondary outcome measures included new medical co-morbidities, postoperative medical or surgical complications, discharge to a higher level of dependency and 30-day readmission rate. RESULTS: A total of 176 patients were included in the final analysis (control 91, intervention 85). Geometric mean length of stay was 5·53 days in the control group and 3·32 days in the intervention group (ratio of geometric means 0·60, 95 per cent c.i. 0·46 to 0·79; P < 0·001). There was a lower incidence of delirium (11 versus 24 per cent; P = 0·018), cardiac complications (8 versus 27 per cent; P = 0·001) and bladder/bowel complications (33 versus 55 per cent; P = 0·003) in the intervention group compared with the control group. Patients in the intervention group were less likely to require discharge to a higher level of dependency (4 of 85 versus 12 of 91; P = 0·051). CONCLUSION: In this study of patients aged 65 years or older undergoing vascular surgery, preoperative comprehensive geriatric assessment was associated with a shorter length of hospital stay. Patients undergoing assessment and optimization had a lower incidence of complications and were less likely to be discharged to a higher level of dependency. Registration number: ISRCTN23142588 (http://www.controlled-trials.com).

Doing More with Less: Diagnostic Accuracy of CT in Suspected Cauda Equina Syndrome.

BACKGROUND AND PURPOSE: Cauda equina syndrome typically requires emergent MR imaging to detect compressive lesions on the cauda equina, which may require surgical decompression. While CT is sometimes performed as a complementary imaging technique to evaluate osseous integrity in patients with cauda equina syndrome, the accuracy of CT in detecting significant spinal stenosis and cauda equina impingement is not well-defined in the literature. We hypothesized that percentage thecal sac effacement on CT of the lumbar spine would have high sensitivity and high negative predictive value in evaluating significant spinal stenosis and cauda equina impingement. MATERIALS AND METHODS: We analyzed imaging studies for 151 consecutive patients with clinically suspected cauda equina syndrome. The percentage thecal sac effacement (<50%, ≥50%) was determined on CT and MR imaging. The presence or absence of cauda equina impingement was determined on MR imaging. Using MR imaging as the reference standard, we performed statistical analysis to determine the accuracy of CT in predicting significant spinal stenosis (percentage thecal sac effacement, ≥50%) and cauda equina impingement. RESULTS: Forty of 151 patients had a percentage thecal sac effacement of ≥50% on MR imaging. Nineteen of 40 had cauda equina impingement. Readers determined that there was a CT percentage thecal sac effacement of <50% in 97/151 cases, and CT percentage thecal sac effacement of ≥50% in 54/151 cases. Reader sensitivity for the detection of significant spinal stenosis (MR percentage thecal sac effacement of ≥50%) was 0.98; specificity, 0.86; positive predictive value, 0.72; and negative predictive value, 0.99. No cases read as CT percentage thecal sac effacement of <50% were found to have cauda equina impingement. CONCLUSIONS: CT percentage thecal sac effacement of ≥50% predicts significant spinal stenosis on MR imaging in patients with clinically suspected cauda equina syndrome. CT percentage thecal sac effacement of <50% appears to reliably rule out cauda equina impingement. This imaging marker may serve as an additional tool for the clinician in deciding whether MR imaging can be deferred.

The bowel cancer awareness campaign 'Be Clear on Cancer': sustained increased pressure on resources and over-accessed by higher social grades with no increase in cancer detected.

AIM: To evaluate the impact of the national 'Be Clear on Cancer' bowel cancer reminder campaign on service and diagnosis at a single UK institution. Secondly, to evaluate the socio-economic background of patients referred before and after the reminder campaign compared with the regional demographic. METHOD: Suspected cancer 2-week wait patients in the 3 months precampaign, postcampaign and after the reminder campaign were included. Demographics, investigations and diagnosis were recorded. The postcode was used to allocate a National Readership Survey social grade. RESULTS: Three hundred and eighty-three referrals were received in the 3 months precampaign, 550 postcampaign and 470 postreminder campaign. There were significant increases in the monthly referral rates following the campaign (P < 0.001 in both the post- and postreminder periods). Significantly more patients from social grades AB and C1C2 than expected from regional demographics were referred precampaign and after the reminder campaign (P < 0.001 in each case). There were no significant differences between the proportions of patients diagnosed with colorectal cancer in the three study periods (P = 0.710). CONCLUSION: The 'Be Clear on Cancer' bowel cancer campaign has had a significant sustained impact on resources. It has failed to increase referrals among lower socio-economic grades, leading to an increase in 'worried well' referrals and no change in numbers, or the stage, of colorectal cancers diagnosed.

Routine screening for pain combined with a pain treatment protocol in head and neck cancer: a randomised controlled trial.

BACKGROUND: We compared the effectiveness and cost of a pain screening and treatment program, with usual care in head and neck cancer patients with significant pain. METHODS: Patients were screened for the presence of pain and then randomly assigned to either an intervention group, consisting of a pain treatment protocol and an education program, or to usual care. Primary outcome was change in the Pain Severity Index (PSI) over three months. RESULTS: We screened 1074 patients of whom 156 were randomized to either intervention or usual care. Mean PSI was reduced over three months in both groups, with no significant difference between the two groups. The Pain Management Index (PMI) at three months, was significantly improved in the intervention group compared with usual care (P<0.001), as was Patient Satisfaction (mean difference in scores was statistically significant: -0.30 [-0.60 to -0.15]). All subjects reported clinically significant levels of anxiety and depression throughout the study. Treatment costs were significantly higher for intervention (mean=£400) compared with usual care (£200), with a low likelihood of being cost-effective. CONCLUSIONS: There was no difference in the Pain Severity Index between the two groups. However there were significant improvements in the intervention group in patient satisfaction and PMI. The pain screening process itself was effective. Sufficient benefit was demonstrated as a result of the intervention to allow continued development of pain treatment pathways, rather than allowing pain treatment to be left to nonformalised ad hoc arrangements.

How should a district general hospital immunology service screen for anti-nuclear antibodies? An 'in-the-field' audit.

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISA(NEG) HEp-2(POS) ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen.

Estimating dichotomised outcomes in two groups with unequal variances: a distributional approach.

Dichotomisation in medical research is sometimes necessary for decision-making or communication purposes. This practice has been criticised in the case of continuous data, and it has been said that means should be compared instead. However when the two groups have unequal variances, comparing means might not show the whole picture as a particular group with a risk defined by a threshold in an outcome may have been affected differently by an intervention than when there is a simple shift of distribution. A statistically sound method using a distributional approach for the dichotomisation of normally distributed outcomes has been described under the assumption of equal variances. This assumption is not sustainable in some situations, and in this work, we develop the method further to cover the case of unequal variances. Through examples from the literature and our own data, we illustrate the effect of unequal variance on dichotomised estimates and present a validation of the method through simulations.

Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Unmasking masked hypertension: prevalence, clinical implications, diagnosis, correlates and future directions.

'Masked hypertension' is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15-30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared with sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment and areas for future research.

Modelling the hierarchical structure in datasets with very small clusters: a simulation study to explore the effect of the proportion of clusters when the outcome is continuous.

In cluster-randomised trials, the problem of non-independence within clusters is well known, and appropriate statistical analysis documented. Clusters typically seen in cluster trials are large in size and few in number, whereas datasets of preterm infants incorporate clusters of size two (twins), size three (triplets) and so on, with the majority of infants being in 'clusters' of size one. In such situations, it is unclear whether adjustment for clustering is needed or even possible. In this paper, we compared analyses allowing for clustering (linear mixed model) with analyses ignoring clustering (linear regression). Through simulations based on two real datasets, we explored estimation bias in predictors of a continuous outcome in different size datasets typical of preterm samples, with varying percentages of twins. Overall, the biases for estimated coefficients were similar for linear regression and mixed models, but the standard errors were consistently much less well estimated when using a linear model. Non-convergence was rare but was observed in approximately 5% of mixed models for samples below 200 and percentage of twins 2% or less. We conclude that in datasets with small clusters, mixed models should be the method of choice irrespective of the percentage of twins. If the mixed model does not converge, a linear regression can be fitted, but standard error will be underestimated, and so type I error may be inflated.

Magnetically driven middle ear ossicles for optical measurement of vibrations in an ear with opened tympanic membrane.

Vibrations of the middle ear ossicles are easily measured by means of laser vibrometry. However, laser vibrometry requires free visual access to the object under investigation, and acquiring free visual access to the ossicles through the ear canal requires the removal of the tympanic membrane (TM), with the result that the ossicles can no longer be stimulated acoustically. To overcome this, we devised a new setup in which the ossicles can be driven magnetically. After measuring the response of the TM to an acoustic signal, we then remove it and attach a small magnet to the exposed manubrium (a part of the most lateral auditory ossicle, the malleus, which is normally attached to the TM). An electromagnetic excitation coil is then used to drive the magnet, and the output to the coil adjusted until the vibration of the manubrium, as measured by the vibrometer, matches that measured in response to the acoustic signal. Such a setup may have uses in research on middle ear mechanics, such as the measurement of nonlinearities in their response, as well as applications in the diagnosis of middle ear conditions such as the fixation of the ossicles by otosclerosis or in chronic otitis media. We describe our setup and discuss the viability of our method and its future clinical potential by presenting some measurements on an artificially fixated ear.