Effect of foot orthoses vs sham insoles on first metatarsophalangeal joint osteoarthritis symptoms: a randomized controlled trial.

OBJECTIVES: To compare contoured foot orthoses to sham flat insoles for first MTP joint OA walking pain. DESIGN: This was a participant- and assessor-blinded, sham-controlled, multi-centre randomized clinical trial set in community-based private practices. Eighty-eight adults aged ≥45 years with symptomatic radiographic first MTP joint OA were randomized to receive contoured foot orthoses (n = 47) or sham flat insoles (n = 41), worn at all times when wearing shoes for 12 weeks. Primary outcome was change in first MTP joint walking pain (11-point numerical rating scale (NRS), 0-10) over 12 weeks. Secondary outcomes included additional first MTP joint and foot pain measures, physical function, quality of life and physical activity. Separate linear regression models for primary and secondary outcomes on treatment group were fit, adjusting for the outcome at baseline and podiatrist. Other measures included adverse events. RESULTS: 88 participants were randomized and 87 (99%) completed the 12-week primary outcome. There was no evidence foot orthoses were superior to sham insoles for reducing pain (mean difference -0.3 NRS units (95% CI -1.2 to 0.6), p = 0.53). Similarly, foot orthoses were not superior to sham on any secondary outcomes. Sensitivity analyses yielded similar results. Adverse events were generally minor and transient. CONCLUSION: Contoured foot orthoses are no more effective than flat sham insoles for the clinical management of first MTP joint OA. Given the dearth of evidence on treatments for first MTP joint OA, further research is needed to identify effective management approaches for this common and debilitating condition.

"It's the single best thing I've done in the last 10 years": a qualitative study exploring patient and dietitian experiences with, and perceptions of, a multi-component dietary weight loss program for knee osteoarthritis.

OBJECTIVE: Explore patient and dietitian experiences with a multi-component dietary weight loss program for knee osteoarthritis to understand enablers and challenges to success at 6-months. DESIGN: Qualitative study embedded within a randomised controlled trial. Semi-structured individual interviews with 24 patients with knee osteoarthritis who undertook, and five dietitians who supervised, a weight management program (involving a ketogenic very low calorie diet (VLCD), video consultations, educational resources) over 6 months. Data were thematically analysed. RESULTS: Five themes were developed: (1) ease and convenience of program facilitated adherence (structure and simplicity of the meal replacements; not feeling hungry on diet; convenience of consulting via video) (2) social and professional support crucial for success (encouragement from partner, family, and friends; guidance from, and accountability to, dietitian; anxiety around going at it alone) (3) program was engaging and motivating (determination to stick to program; rapid weight loss helped motivation) (4) holistic nature of program was important (suite of high-quality educational resources; exercise important to compliment weight loss) (5) rewarding experience and lifelong impact (improved knee pain and function; positive lifestyle change). CONCLUSIONS: Patients and dietitians described positive experiences with the weight management program, valuing its simplicity, effectiveness, and convenience. Support from dietitians and a comprehensive suite of educational resources, incorporated with an exercise program, were considered crucial for success. Findings suggest this multi-component dietary program is an acceptable weight loss method in people with knee osteoarthritis that may benefit symptoms. Strategies for supporting long-term independent weight management should be a focus of future research.

Cognitive processing speed in multiple sclerosis clinical practice: association with patient-reported outcomes, employment and magnetic resonance imaging metrics.

BACKGROUND AND PURPOSE: To analyze the relationship between cognitive processing speed, patient-reported outcome measures (PROMs), employment and magnetic resonance imaging (MRI) metrics in a large multiple sclerosis cohort. METHODS: Cross-sectional clinical data, PROMs, employment and MRI studies within 90 days of completion of the Processing Speed Test (PST), a technology-enabled adaptation of the Symbol Digit Modalities Test, were collected. MRI was analyzed using semi-automated methods. Correlations of PST score with PROMs and MRI metrics were examined using Spearman's rho. Wilcoxon rank sum testing compared MRI metrics across PST score quartiles and linear regression models identified predictors of PST performance. Effects of employment and depression were also investigated. RESULTS: In 721 patients (mean age 47.6 ± 11.4 years), PST scores were significantly correlated with all MRI metrics, including cord atrophy and deep gray matter volumes. Linear regression demonstrated self-reported physical disability, cognitive function, fatigue and social domains (adjusted R2  = 0.44, P < 0.001) as the strongest clinical predictors of PST score, whereas that of MRI variables included T2 lesion volume, whole-brain fraction and cord atrophy (adjusted R2  = 0.42, P < 0.001). An inclusive model identified T2 lesion volume, whole-brain fraction, self-reported upper extremity function, cognition and social participation as the strongest predictors of PST score (adjusted R2  = 0.51, P < 0.001). There was significant effect modification by depression on the relationship between self-reported cognition and PST performance. Employment status was associated with PST scores independent of age and physical disability. CONCLUSION: The PST score correlates with PROMs, MRI measures of focal and diffuse brain injury, and employment. The PST score is a feasible and meaningful measure for routine multiple sclerosis care.

Supporting mental health service users to stop smoking: findings from a process evaluation of the implementation of smokefree policies into two mental health trusts.

BACKGROUND: Life expectancy is 10-20 years lower among people with a severe mental health disorder. Most of these early deaths are due to chronic conditions, including cardiovascular and respiratory diseases. Smoking is a major risk factor for these conditions and introducing smokefree policies has been recommended to mental health service providers in England by the National Institute for Health and Care Excellence (NICE), in their Public Health Guideline 48: Smoking: acute, maternity and mental health services. This paper reports a process evaluation of introducing these policy recommendations, which were updated in 2013. METHOD: Process data were collected through semi-structured interviews with staff (n = 51), members of partnering organisations (n = 5), service users (n = 7) and carers (n = 2) between November 2016 - April 2017. Normalization Process Theory (NPT) was used to design the data collection tools and analyse the data. A framework approach was taken with the analysis, using the four concepts of NPT: coherence, cognitive participation, collective action and reflexive monitoring. RESULTS: The policy made sense to some staff, patients and carers (coherence) who 'bought-into' the idea (cognitive participation) but other participants disagreed. Although smokefree policies were operationalised (collective action), sometimes they were opposed. Progress was made, especially in some units, but continued to be resisted in others. Informal appraisal of progress (reflexive monitoring) presented a varied picture. CONCLUSION: Some progress has been made in terms of changing an entrenched, smoking culture into one that is smokefree on Trust sites across the region. Perseverance and resourcing over the long-term is required to establish a non-smoking culture in on-site provision of mental health services.

Top-down design of magnonic crystals from bottom-up magnetic nanoparticles through protein arrays.

We show that chemical fixation enables top-down micro-machining of large periodic 3D arrays of protein-encapsulated magnetic nanoparticles (NPs) without loss of order. We machined 3D micro-cubes containing a superlattice of NPs by means of focused ion beam etching, integrated an individual micro-cube to a thin-film coplanar waveguide and measured the resonant microwave response. Our work represents a major step towards well-defined magnonic metamaterials created from the self-assembly of magnetic nanoparticles.

Pt, Co-Pt and Fe-Pt alloy nanoclusters encapsulated in virus capsids.

Nanostructured Pt-based alloys show great promise, not only for catalysis but also in medical and magnetic applications. To extend the properties of this class of materials, we have developed a means of synthesizing Pt and Pt-based alloy nanoclusters in the capsid of a virus. Pure Pt and Pt-alloy nanoclusters are formed through the chemical reduction of [PtCl4](-) by NaBH4 with/without additional metal ions (Co or Fe). The opening and closing of the ion channels in the virus capsid were controlled by changing the pH and ionic strength of the solution. The size of the nanoclusters is limited to 18 nm by the internal diameter of the capsid. Their magnetic properties suggest potential applications in hyperthermia for the Co-Pt and Fe-Pt magnetic alloy nanoclusters. This study introduces a new way to fabricate size-restricted nanoclusters using virus capsid.

Is endometrial ablation protective against endometrial cancer? A retrospective observational study.

STUDY OBJECTIVES: Endometrial ablation has been increasingly used over the last 30 years to manage patients with dysfunctional uterine bleeding. Of primary concern, however, is the potential of the procedure to mask the presence or delay the diagnosis of endometrial cancer. The aim of this study is to assess the long-term effects of endometrial ablation and its association with the development of endometrial cancer. METHODS: This is a retrospective observational study that was conducted at Bradford Teaching Hospitals in the United Kingdom. The study included all women who had different types of endometrial ablative procedures in the period of January 1994 to December 2011. Analysis of the data was performed using SPSS for windows (V9) software package. RESULTS: Over 18 years period, 1521 women had endometrial ablative procedures for dysfunctional uterine bleeding. During their long-term follow-up, none of the women developed endometrial cancer later in life. This incidence is much lower than the lifetime risk of endometrial cancer in the general population (RR 0.0135; 95 % CI 0.0007-0.2801; P = 0.0054). CONCLUSION: To our knowledge, this is the largest study to examine the long-term incidence of endometrial cancer in women who had endometrial ablative procedures. It shows that the development of endometrial cancer does not seem to be associated with endometrial ablative procedures.

Do postmenopausal women with thickened endometrium on trans-vaginal ultrasound in the absence of vaginal bleeding need hysteroscopic assessment? A Pilot Study.

We aimed to determine the incidence of endometrial cancer in a cohort of postmenopausal women with thickened endometrium but no bleeding referred for hysteroscopy and determine the risk estimate of cancer using a cut-off of > 11 mm. This retrospective study of asymptomatic postmenopausal women with thickened endometrium on trans-vaginal scan referred for hysteroscopy was performed using data from 2008 to 2010. In total 63 women were identified. 2 cases of endometrial cancer were identified with an incidence of 3.17%. 22 cases had endometrial thickness (ET) > 11 mm of which 2 were malignant giving a risk estimate for endometrial cancer of 9.1%. 61 women had benign pathology, 40.98% had atrophic endometrium and 59.02% had benign polyp. In conclusion, the incidence of endometrial cancer in postmenopausal women with thickened endometrium on transvaginal scan without vaginal bleeding is low and ET of 11 mm or more seems realistic to use as a cut-off for referral for hysteroscopy.

Direct measurement of the round window niche dimensions using a 3-dimensional moulding technique--a human cadaveric temporal bone study.

OBJECTIVES: To directly measure the various dimensions of the RWN focusing on the bony overhang and the vertical height between the free margin of the bony overhang and floor of the niche. DESIGN: Laboratory-based anatomical study using formalin-preserved human cadaveric temporal bones. SETTING: Temporal Bone laboratory, Department of Otolaryngology University of Dundee Medical School & Ninewells Hospital, Dundee, UK. PARTICIPANTS: NA. MAIN OUTCOME MEASURES: Three measurements were carried out (i) the depth of the round window niche extending from the free margin of the bony overhang to the fundus; (ii) vertical height from the free margin of the overhang to the floor of the niche (entrance) and (iii) the antero-posterior (AP) dimension of the niche. RESULTS: Based on mould technique, the three dimensions were calculated as follows: mean bony overhang = 2.1 mm (range 1.9-2.4 mm), height of RWN = 2.0 mm (1.8-2.15 mm) and AP length = 4.0 mm (3.3-4.95 mm). CONCLUSIONS: Our data demonstrate that the mean dimension of the bony overhang superior to the RWM is 2.1 mm.

Protein brownian rotation at the glass transition temperature of a freeze-concentrated buffer probed by superparamagnetic nanoparticles.

For applications from food science to the freeze-thawing of proteins it is important to understand the often complex freezing behavior of solutions of biomolecules. Here we use a magnetic method to monitor the Brownian rotation of a quasi-spherical cage-shaped protein, apoferritin, approaching the glass transition Tg in a freeze-concentrated buffer (Tris-HCl). The protein incorporates a synthetic magnetic nanoparticle (Co-doped Fe3O4 (magnetite)). We use the magnetic signal from the nanoparticles to monitor the protein orientation. As T decreases toward Tg of the buffer solution the protein's rotational relaxation time increases exponentially, taking values in the range from a few seconds up to thousands of seconds, i.e., orders of magnitude greater than usually accessed, e.g., by NMR. The longest relaxation times measured correspond to estimated viscosities >2 MPa s. As well as being a means to study low-temperature, high-viscosity environments, our method provides evidence that, for the cooling protocol used, the following applies: 1), the concentration of the freeze-concentrated buffer at Tg is independent of its initial concentration; 2), little protein adsorption takes place at the interface between ice and buffer; and 3), the protein is free to rotate even at temperatures as low as 207 K.

Identification of Lactobacillus strains with probiotic features from the bottlenose dolphin (Tursiops truncatus).

AIMS: In order to develop complementary health management strategies for marine mammals, we used culture-based and culture-independent approaches to identify gastrointestinal lactobacilli of the common bottlenose dolphin, Tursiops truncatus. METHODS AND RESULTS: We screened 307 bacterial isolates from oral and rectal swabs, milk and gastric fluid, collected from 38 dolphins in the U.S. Navy Marine Mammal Program, for potentially beneficial features. We focused our search on lactobacilli and evaluated their ability to modulate TNF secretion by host cells and inhibit growth of pathogens. We recovered Lactobacillus salivarius strains which secreted factors that stimulated TNF production by human monocytoid cells. These Lact. salivarius isolates inhibited growth of selected marine mammal and human bacterial pathogens. In addition, we identified a novel Lactobacillus species by culture and direct sequencing with 96·3% 16S rDNA sequence similarity to Lactobacillus ceti. CONCLUSIONS: Dolphin-derived Lact. salivarius isolates possess features making them candidate probiotics for clinical studies in marine mammals. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to isolate lactobacilli from dolphins, including a novel Lactobacillus species and a new strain of Lact. salivarius, with potential for veterinary probiotic applications. The isolation and identification of novel Lactobacillus spp. and other indigenous microbes from bottlenose dolphins will enable the study of the biology of symbiotic members of the dolphin microbiota and facilitate the understanding of the microbiomes of these unique animals.

Sentinel node identification using microbubbles and contrast-enhanced ultrasonography.

Sentinel lymph node (SLN) biopsy has become the recommended method for surgical staging of the axilla in patients with breast cancer. Grey-scale axillary ultrasonography (US) combined with US-guided biopsy is a widely used preoperative staging procedure but has limited sensitivity. US contrast agent "microbubbles", when injected intradermally, have been shown to have the potential to enter the breast lymphatics, travel rapidly to the axilla, and visualize the putative SLNs. This review illustrates the SLN identification technique using intradermal injection of microbubbles and contrast-enhanced US. The injection method, lymphatic visualization techniques, grey-scale and contrast-enhanced US images of the putative SLNs are reviewed and exemplified.

Clinically palpable breast abnormalities with normal imaging: is clinically guided biopsy still required?

AIM: To determine the need for a fine-needle or core biopsy in patients with clinically palpable breast abnormalities who have negative mammographic and sonographic findings. METHOD AND MATERIALS: Over a 12-year period, 251 patients with a palpable abnormality at presentation and who had a negative ultrasound and mammogram underwent clinically guided biopsy (CGB) by breast surgeons. This was 2.7% (251/9313) of all breast biopsies performed from January 1999 to December 2010. Physical findings were qualitatively categorized into five groups as clinically "normal", "benign", "probably benign", "suspicious", and "malignant" at the time of initial assessment. The number of biopsies for each category and biopsy results were analysed retrospectively. RESULTS: Three (1.2%) of the 251 CGBs were reported as malignant; two (0.8%) of which were invasive. Forty-six (18.3%) of the 251 cases were regarded as clinically suspicious or malignant while the remaining 215 examinations were categorized as benign or probably benign. All three malignancies were in the clinically suspicious or malignant group. CONCLUSION: A negative ultrasound and mammogram in patients with a palpable abnormality does not exclude breast cancer; however, the likelihood is very low (1.2%). In this study, 81.7% of biopsies (205/251) could have been avoided if CGB was reserved for the clinically suspicious or malignant group only without missing any malignancies.

Defining performance levels in undergraduate otolaryngology education.

OBJECTIVES: This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology. METHODS: A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group. Data were collected from a wide range of doctors. RESULTS: Participants felt that graduating students should be able to: recognise, assess and initiate management for common and life-threatening acute conditions; take an appropriate patient history; and perform an appropriate examination for the majority of otolaryngology clinical conditions but manage only a select few. CONCLUSION: This study reports performance levels for otolaryngology topics at an undergraduate level. Participating doctors felt that a higher level of performance should be expected of students treating life-threatening, acute and common otolaryngology conditions.

Dormancy dampens the microbial distance-decay relationship.

Much of Earth's biodiversity has the capacity to engage in dormancy, a reversible state of reduced metabolic activity. By increasing resilience to unfavourable conditions, dormancy leads to the accumulation of 'seed banks'. These reservoirs of genetic and phenotypic diversity should diminish the strength of environmental filtering and increase rates of dispersal. Although prevalent among single-celled organisms, evidence that dormancy influences patterns of microbial biogeography is lacking. We constructed geographical and environmental distance-decay relationships (DDRs) for the total (DNA) and active (RNA) portions of bacterial communities in a regional-scale 16S rRNA survey of forested ponds in Indiana, USA. As predicted, total communities harboured greater diversity and exhibited weaker DDRs than active communities. These observations were robust to random resampling and different community metrics. To evaluate the processes underlying the biogeographic patterns, we developed a platform of mechanistic models that used the geographical coordinates and environmental characteristics of our study system. Based on more than 106 simulations, our models approximated the empirical DDRs when there was strong environmental filtering along with the presence of long-lived seed banks. By contrast, the inclusion of dispersal generally decreased model performance. Together, our findings support recent theoretical predictions that seed banks can influence the biogeographic patterns of microbial communities. This article is part of the theme issue 'Conceptual challenges in microbial community ecology'.

Balloon Eustachian tuboplasty for Eustachian tube dysfunction: report of long-term outcomes in a UK population.

BACKGROUND: Balloon Eustachian tuboplasty is a surgical management option for Eustachian tube dysfunction; it has shown promising results in studies worldwide, but has had limited uptake in the UK. This study reports long-term outcomes for patients offered balloon Eustachian tuboplasty for chronic dilatory and baro-challenge-induced Eustachian tube dysfunction, and describes practical experience gained from its implementation. METHODS: Balloon Eustachian tuboplasty was conducted in 25 patients (36 ears) with Eustachian tube dysfunction over three years. Information on presenting symptoms and signs, audiometric findings, tympanometry, and Eustachian Tube Dysfunction Questionnaire-7 scores were recorded pre- and post-operatively with a minimum follow up of one year. RESULTS: Sixteen (64 per cent) of the 25 patients demonstrated symptom resolution after balloon Eustachian tuboplasty according to the Eustachian Tube Dysfunction Questionnaire-7. Fourteen (64 per cent) of the 22 patients with a type B or C tympanogram pre-operatively, had a type A trace post-operatively. Fifteen (75 per cent) of 20 patients with pre-operative conductive hearing loss showed improvement post-operatively, and 11 (50 per cent) of 22 patients with pre-operative middle-ear effusion or tympanic membrane retraction showed resolution. CONCLUSION: Balloon Eustachian tuboplasty can improve subjective and objective measures of Eustachian tube dysfunction, and provide longer-term resolution.

A case of verocytotoxin-producing Escherichia coli O157 from a private barbecue in South East England.

The following case report describes a cluster of Escherichia coli O157 cases in the United Kingdom related to undercooked beef at a barbecue, resulting in an intensive care admission in France with haemolytic uraemic syndrome and highlighting the need to cook beef properly.

Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.

BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.

The effect of auditory stimulation on the tensor tympani in patients following stapedectomy.

CONCLUSION: We believe that a tensor tympani reflex, in response to loud sound, is present in a minority of people, although its functional significance with regard to sound transmission is questionable. The absence of startle response in our stapedectomized subjects makes us question whether the tensor component of the startle response is large enough to be identified by manometry. OBJECTIVES: This study was organized to examine reflex activity to stimulation by loud sound or by startle in the tensor tympani. Although many previous studies have been carried out, results have been contradictory, and methodological flaws have rendered the interpretations questionable. PATIENTS AND METHODS: Stapedectomized patients were invited to take part in the study. Thirteen patients underwent testing by extratympanic manometry, using a standard tympanometer. Responses were observed during repeated stimuli with loud sound at 500, 1000, 2000 and 4000 Hz to the ipsilateral and contralateral ears, and with an air jet against the closed eye. A control group was also studied for the startle test. RESULTS: Three clear ipsilateral (23%) and two clear contralateral (14%) responses to auditory stimuli were seen in the 13 patients. We found responses to startle stimuli in none of our study group and eight (42%) of control ears.