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We characterised the aetiology of non-responsive coeliac disease (NRCD) and provided contemporary mortality data in refractory coeliac disease (RCD) from our centre. We also measured urine gluten immunogenic peptides (GIPs) in patients with established RCD1 to evaluate gluten exposure in these individuals. Methods: This was a longitudinal cohort study conducted in Sheffield, UK. Between 1998 and 2019, we evaluated 285 adult (≥16 years) patients with NRCD or RCD. Patients with established RCD1 and persisting mucosal inflammation and/or ongoing symptoms provided three urine samples for GIP analysis. Results: The most common cause of NRCD across the cohort was gluten exposure (72/285; 25.3%). RCD accounted for 65/285 patients (22.8%), 54/65 patients (83.1%) had RCD1 and 11/65 patients (16.9%) had RCD2. The estimated 5-year survival was 90% for RCD1 and 58% for RCD2 (p = 0.016). A total of 36/54 (66.7%) patients with RCD1 underwent urinary GIP testing and 17/36 (47.2%) had at least one positive urinary GIP test. Conclusion: The contemporary mortality data in RCD2 remains poor; patients with suspected RCD2 should be referred to a recognised national centre for consideration of novel therapies. The high frequency of urinary GIP positivity suggests that gluten exposure may be common in RCD1; further studies with matched controls are warranted to assess this further.

Background and aim\ud \ud Gluten neuropathy (GN) is a common neurological manifestation of gluten sensitivity (GS), characterized by serological evidence of GS, while other risk factors for developing neuropathy are absent. The degree of small fiber dysfunction in GN has not been studied in depth to date. Small fiber involvement may lead to pain, thermal perception abnormalities, and sweat gland dysfunction. Sudomotor innervation refers to the cholinergic innervation of the sympathetic nervous system through small fibers in the sweat glands. The aim of our study was to assess the sudomotor function of GN patients.\ud \ud \ud \ud Methods\ud \ud Patients with GN were recruited. Clinical and neurophysiological data were obtained. HLA-DQ genotyping was performed. The skin electrochemical conductance (ESC) was measured with SUDOSCANTM.\ud \ud \ud \ud Results\ud \ud Thirty-two patients (25 males, mean age 69.5±10.2 years) were recruited. Thirteen patients (40.6%) had abnormal sudomotor function of the hands. Sixteen patients (50%) had abnormal sudomotor function of the feet. Twenty-one patients (65.6%) had abnormal sudomotor function of either the hands or feet.\ud \ud \ud \ud Sudomotor dysfunction did not correlate with the type of neuropathy (length-dependent neuropathy or sensory ganglionopathy), gluten-free diet adherence, severity of neuropathy, and duration of disease or HLA-DQ genotype. No differences in the ESC were found between patients with painful and patients with painless GN.\ud \ud \ud \ud Conclusion\ud \ud Sudomotor dysfunction affects two-thirds of patients with GN. The lack of correlation between pain and sudomotor dysfunction suggests different patterns of small fiber involvement in patients with GN.

We have previously shown that 67% of patients with newly diagnosed coeliac disease (CD) presenting to gastroenterologists have evidence of neurological dysfunction. This manifested with headache and loss of co-ordination. Furthermore 60% of these patients had abnormal brain imaging. In this follow-up study, we re-examined and re-scanned 30 patients from the original cohort of 100, seven years later. There was significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Although those patients with coordination problems at baseline reported improvement on the gluten free diet (GFD), there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more gluten-sensitivity related antibodies at follow-up. In total, 50% of the whole follow-up cohort were positive for one or more gluten-related antibodies. A comparison between the baseline and follow-up brain imaging showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group. Patients with CD who do not adhere to a strict GFD and are serological positive are at risk of developing ataxia, and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. This highlights the importance of regular review and close monitoring.

Introduction: Cerebellar degeneration has been associated in patients with epilepsy, though the exact pathogenic mechanisms are not understood. The aim of this systematic review was to identify the prevalence of cerebellar degeneration in patients with epilepsy and identify any pathogenic mechanisms. Methodology: A systematic computer-based literature search was conducted using the PubMed database. Data extracted included prevalence, clinical, neuroradiological, and neuropathological characteristics of patients with epilepsy and cerebellar degeneration. Results: We identified three consistent predictors of cerebellar degeneration in the context of epilepsy in our review: temporal lobe epilepsy, poor seizure control, and phenytoin as the treatment modality. Whole brain and hippocampal atrophy were also identified in patients with epilepsy. Conclusions: Cerebellar degeneration is prevalent in patients with epilepsy. Further prospective studies are required to confirm if the predictors identified in this review are indeed linked to cerebellar degeneration and to establish the pathogenic mechanisms that result in cerebellar insult.

Background\ud The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta‐analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied.\ud \ud Methods\ud After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups.\ud \ud Results\ud Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%‐3.2%) and 2.7% (95% CI 2.0%‐3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%‐22.6%) and 13.6% (95% CI 11.6%‐15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75‐3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness.\ud \ud Secondary meta‐analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14‐7.40) and 2.93 times higher (95% CI 1.41‐6.07), respectively, in the active treatment groups compared to placebo.\ud \ud Conclusions\ud TMS is a safe and well‐tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice.

Background: The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta-analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied. Methods: After a systematic Medline search for TMS randomized controlled trials (RCTs), we assessed the number of patients reporting at least one AE and the number of discontinuations because of AE in active and sham TMS groups. Results: Data were extracted from 93 RCTs. The overall pooled estimate of active TMS and placebo treated patients who discontinued treatment because of AEs was 2.5% (95% CI 1.9%-3.2%) and 2.7% (95% CI 2.0%-3.5%), respectively. The pooled estimate of active TMS and placebo treated patients experiencing at least one AE was 29.3% (95% CI 19.0%-22.6%) and 13.6% (95% CI 11.6%-15.8%), respectively, suggesting that the odds of experiencing an AE is 2.60 times higher (95% CI 1.75-3.86) in the active treatment group compared to placebo (p < 0.00001). The most common AE was headache, followed by dizziness. Secondary meta-analyses in depression and psychotic disorders showed that the odds of experiencing an AE is 3.98 times higher (95% CI 2.14-7.40) and 2.93 times higher (95% CI 1.41-6.07), respectively, in the active treatment groups compared to placebo. Conclusions: TMS is a safe and well-tolerated intervention. Nocebo phenomena do occur during TMS treatment and should be acknowledged during clinical trial design and daily clinical practice. © 2019 International Neuromodulation Society

Background & Aims\ud Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to TG6 increases the risk of neurologic defects in patients with a new diagnosis of celiac disease.\ud \ud Methods\ud We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging (MRI) of the brain, MR spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction.\ud \ud Results\ud Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from the MRI, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients–these patients had significant atrophy of subcortical brain regions compared to patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later.\ud \ud Conclusions\ud In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurological deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurological manifestations amongst clinicians and reinforcement of adherence to a strict GFD by patients in order to avoid permanent neurological disability.

Introduction\ud \ud Tremor is a common side effect of treatment with lithium. Its characteristics can vary and when less rhythmical, distinction from myoclonus can be difficult.\ud \ud \ud \ud Methods\ud \ud We identified 8 patients on long-term treatment with lithium that developed upper limb tremor. All patients were assessed clinically and electrophysiologically, with jerk-locked averaging (JLA) and cross-correlation (CC) analysis, and five of them underwent brain MRI examination including spectroscopy (MRS) of the cerebellum.\ud \ud \ud \ud Results\ud \ud Seven patients (6 female) had action and postural myoclonus and one a regular postural and kinetic tremor that persisted at rest. Mean age at presentation was 58 years (range 42–77) after lengthy exposure to lithium (range 7–40 years). During routine monitoring all patients had lithium levels within the recommended therapeutic range (0.4-1 mmol/l). There was clinical and/or radiological evidence (on cerebellar MRS) of cerebellar dysfunction in 6 patients. JLA and/or CC suggested a cortical generator of the myoclonus in seven patients. All seven were on antidepressants and three additionally on neuroleptics, four of them had gluten sensitivity and two reported alcohol abuse.\ud \ud \ud \ud Conclusions\ud \ud A synergistic effect of different factors appears to be contributing to the development of cortical myoclonus after chronic exposure to lithium. We hypothesise that the cerebellum is involved in the generation of cortical myoclonus in these cases and factors aetiologically linked to cerebellar pathology like gluten sensitivity and alcohol abuse may play a role in the development of myoclonus. Despite the very limited evidence in the literature, lithium induced cortical myoclonus may not be so rare.

Both nuclear and mitochondrial DNA defects can cause isolated cytochrome c oxidase (COX; complex IV) deficiency, leading to the development of the mitochondrial disease. We report a 52-year-old female patient who presented with a late-onset, progressive cerebellar ataxia, tremor and axonal neuropathy. No family history of neurological disorder was reported. Although her muscle biopsy demonstrated a significant COX deficiency, there was no clinical and electromyographical evidence of myopathy. Electrophysiological studies identified low frequency sinusoidal postural tremor at 3 Hz, corroborating the clinical finding of cerebellar dysfunction. Complete sequencing of the mitochondrial DNA genome in muscle identified a novel MT-CO2 variant, m.8163A>G predicting p.(Tyr193Cys). We present several lines of evidence, in proving the pathogenicity of this heteroplasmic mitochondrial DNA variant, as the cause of her clinical presentation. Our findings serve as an important reminder that full mitochondrial DNA analysis should be included in the diagnostic pipeline for investigating individuals with spinocerebellar ataxia.

Chronic idiopathic axonal polyneuropathy (CIAP) is a disorder with insidious onset and slow progression, where no etiology is identified despite appropriate investigations. We aimed to investigate the role of oxidative stress as a risk factor for the pathogenesis of CIAP. Sera of patients with CIAP were tested for protein carbonyl (PC) and 8-hydroxydeoxyguanosine (8H). As a control group, we recruited patients with gluten neuropathy. Twenty-one patients with CIAP and 21 controls were recruited. The two groups did not differ significantly regarding demographics or clinical characteristics (i.e., neuropathy type or disease severity). After adjusting for gender, having CIAP was positively correlated with both the 8H titer (standardized beta coefficient 0.349, p = 0.013) and the PC titer (standardized beta coefficient 0.469, p = 0.001). Oxidative stress appears to be increased in CIAP and might have a role in the pathogenesis of the disease.

Objectives Lower gastrointestinal symptoms are not well characterized in people with type 1 diabetes, and the effects on quality of life and glycemic control are unknown. This study aimed to determine the prevalence of lower gastrointestinal symptoms and the effects on glycemic control and quality of life, and to investigate for underlying causes.\ud \ud \ud Research design and methods This is a prospective, cohort study in secondary care. Patients with type 1 diabetes completed a gastrointestinal symptom questionnaire and the Short Form 36 V.2 quality of life questionnaire and had their hemoglobin A1c measured. Patients with diarrhea were offered reassessment and investigation as per the national guidelines. Controls without diabetes were used to compare symptom prevalence and quality of life scores.\ud \ud \ud Results 706 with type 1 diabetes (mean age 41.9 years) and 604 controls (mean age 41.9 years) were enrolled. Gastrointestinal symptoms were significantly more frequent in type 1 diabetes compared with controls, in particular constipation (OR 2.4), diarrhea (OR 2.5), alternating bowel habit (OR 2.1), abdominal pain (OR 1.4), floating stools (OR 2.7), bloating (OR 1.4) and flatulence (OR 1.3) (all p

Introduction: Nocebo is very prevalent among neurological disorders, resulting in low adherence and treatment outcome. We sought to examine the adverse events (AE) following placebo administration in placebo-controlled randomized clinical trials (RCTs) for chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: After a systematic literature search for RCTs for CIDP pharmacotherapy treatments, we assessed the number of AE in the placebo groups and the number discontinuations because of placebo intolerance. Results: Our literature search strategy revealed 82 papers. Data were extracted from three RCTs fulfilling our inclusion criteria. Approximately two in five placebo-treated patients (42.0%) reported at least one AE and approximately one in fifty placebo-treated patients discontinued placebo treatment because of AEs (2.1%). All patients participating in the CIDP trials reported similar AEs independently of the study arm they belonged. Conclusion: Compared to other neurological diseases the nocebo effect in CIDP is significantly smaller. © 2018 Elsevier B.V.

OBJECTIVES: Mucosal healing is important in celiac disease (CD) for the prevention of complications. However, obtaining duodenal biopsies is invasive, and there is currently no reliable surrogate marker for histological remission in clinical practice. We aimed to assess the role of a point-of-care test (POCT) based on IgA/IgG-deamidated gliadin peptide, in detecting persistent villous atrophy (VA) in CD. \ud \ud METHODS: We prospectively recruited patients with CD attending endoscopy for the assessment of histological remission. All patients had IgA-endomysial (EMA) antibodies, IgA-tissue transglutaminase (TTG) antibodies, and the POCT performed, and completed a validated dietary adherence questionnaire. A gastroscopy was performed in all patients, with four biopsies taken from the second part of the duodenum and one from the duodenal bulb. We compared the diagnostic performance of the surrogate markers against duodenal histology as the reference standard. \ud \ud RESULTS: A total of 217 patients with CD (70% female, age range 16-83 years, median age 53 years) on a gluten-free diet (median duration 6 years) were recruited from 2013 to 2017. Eighty-five (39.2%) patients had persistent VA. The sensitivities of the POCT, TTG, EMA, and the adherence score in detecting VA were 67.1%, 44.7%, 37.7%, and 24.7% respectively (P=0.0005). The combination of the POCT and adherence score only marginally increased the sensitivity to 70.6% (59.7-80.0%). \ud \ud CONCLUSIONS: The sensitivity of the POCT was higher than the other surrogate markers in predicting VA. A POCT may provide the additional advantage of an immediate objective assessment of mucosal healing at the time of an office-based follow-up consultation.

Mitochondrial disease is phenotypically and genetically heterogeneous with an estimated prevalence of 1 in 4,300.1 Mutations in the POLG gene, encoding the catalytic subunit of DNA polymerase gamma, are an important cause of mitochondrial disease. The spectrum of clinical manifestations in POLG-related mitochondrial disease is variable,2 with disease onset ranging from adulthood-onset dominant or recessive progressive external ophthalmoplegia (chronic progressive external ophthalmoplegia), ataxia-neuropathy spectrum, myoclonic epilepsy, myopathy, and sensory ataxia to childhood-onset Alpers syndrome, which is characterized by intractable seizures, psychomotor regression, and hepatic impairment. Epilepsy is a poor prognostic factor in POLG mutations,3 and the onset of epilepsy often clusters in childhood (

Demyelinating forms of Charcot-Marie-Tooth (CMT) result from mutations in a number of genes, the majority of which show an autosomal dominant pattern of inheritance [1]. Recessive patterns of inheritance are less common. We report a case of demyelinating CMT resulting from compound heterozygous mutation in the FGD4 gene.

BACKGROUND & AIMS: The clinical effects of gluten-sensitive\ud enteropathy with villous atrophy limited to the duodenal bulb\ud (D1) have not been delineated in adults with celiac disease. We\ud investigated the sensitivity of D1 biopsy analysis in the detection\ud of celiac disease, the number and sites of biopsies required\ud to detect ultra-short celiac disease (USCD, villous atrophy\ud limited to D1), and the clinical phenotype of USCD. METHODS:\ud We performed a prospective study of 1378 patients (mean age,\ud 50.3 y; 62% female) who underwent endoscopy at a tertiary\ud medical center in the United Kingdom from 2008 through\ud 2014; routine duodenal biopsy specimens were collected from\ud D1 and the second part of the duodenum (D2). Quadrantic D1\ud biopsy specimens were collected from 171 consecutive patients\ud with a high suspicion of celiac disease (mean age, 46.5 y; 64%\ud female). Clinical data from patients diagnosed with USCD, based\ud on biopsy analysis, were compared with those from patients\ud with conventional celiac disease (CCD) (villous atrophy beyond\ud D1) and individuals without celiac disease (controls). The\ud number of intraepithelial lymphocytes (IELs) and immune\ud phenotypes were compared between D1 vs D2 in patients with\ud celiac disease. RESULTS: Of the 1378 patients assessed, 268\ud (19.4%) were diagnosed with celiac disease; 9.7% of these\ud patients had villous atrophy confined to D1 (USCD; P < .0001).\ud Collection of a single additional biopsy specimen from any D1\ud site increased the sensitivity of celiac disease detection by\ud 9.3%–10.8% (P < .0001). Patients with USCD were younger\ud (P ¼ .03), had lower titers of tissue transglutaminase antibody\ud (P ¼ .001), and less frequently presented with diarrhea\ud (P ¼ .001) than patients with CCD. Higher proportions of\ud patients with CCD had ferritin deficiency (P ¼ .007) or folate\ud deficiency (P ¼ .003) than patients with USCD or controls.\ud Patients with celiac disease had a median of 50 IELs/100\ud enterocytes in D1 and a median of 48 IELs/100 enterocytes\ud (P ¼ .7) in D2. The phenotype of IELs from patients with D1\ud celiac disease was indistinguishable from those of patients with\ud D2 celiac disease. CONCLUSIONS: Collection of a single\ud additional biopsy specimen from any site in the D1 intestine\ud increases the sensitivity of detection for celiac disease. Patients\ud with USCD may have early stage or limited celiac disease, with a\ud mild clinical phenotype and infrequent nutritional deficiencies.

OBJECTIVES: Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms\ud without enteropathy that symptomatically benefi t from gluten-free diet (GFD). Little is known about\ud its pathophysiology, propensity to neurological manifestations, and if these differ from patients with\ud coeliac disease (CD). We investigated the clinical and immunological characteristics of patients\ud presenting with neurological manifestations with CD and those with NCGS.\ud METHODS: We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS\ud presenting with neurological dysfunction assessed and followed up regularly over a period of\ud 20 years.\ud RESULTS: Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confi rm\ud CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological\ud dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had\ud evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common\ud neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There\ud was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion\ud of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in\ud Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet.\ud Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in\ud 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and\ud those without as well as those with positive TG2 compared with those with negative TG2 antibodies\ud identifi ed no differences within these subgroups. Serological positivity for TG6 antibodies was similar\ud in the two groups (67 and 60%).\ud CONCLUSIONS: The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD\ud suggestive of common pathophysiological mechanisms.

Background: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1) to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2) to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias.\ud \ud Materials & Methods: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data.\ud \ud Results: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia.\ud \ud Conclusions: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar insult.

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that\ud use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which\ud organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8\ud years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR)\ud versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total\ud body bone mineral density was 5% higher (mean difference 0.05 g/cm2\ud , P = 0.02) and bone turnover was 14% lower (TRAP\ud 5b, mean difference 20.56IU/L, P = 0.006; osteocalcin, mean difference 23.08 ng/mL, P = 0.03) in the hip resurfacing versus\ud conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference 25%, P = 0.04) and\ud left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus\ud those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%,\ud chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a\ud 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference\ud in neuropsychological, renal tubular, hepatic or endocrine function between groups (P.0.05). Our findings of differences in\ud bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in\ud patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients\ud with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate\ud the risk of clinical disease.

Introduction: The health-related quality-of-life (HRQoL) instruments are an important tool for the evaluation of medical outcomes. Sexually transmitted diseases (STDs) influence the patients' life. We aimed to evaluate the HRQoL in patients with anogenital warts at the time of and 1 month after the diagnosis.Materials and methods: We used the short-form (SF)-36 questionnaire to compare the HRQoL of 91 patients with anogenital warts to 53 control subjects with the same socioeconomic characteristics.Results: There was no statistical difference in the overall HRQoL measurement between the anogenital wart patients and controls. However, there was an improvement in the scales of vitality (65.22 ± 15.70 vs. 69.04 ± 14.11, respectively; p < 0.05) and mental health (65.00 ± 20.09 vs. 69.43 ± 18.08, respectively; p < 0.05) in anogenital warts patients between the time of diagnosis and 1 month later. Furthermore, there was a significant deterioration in the scale of social functioning (73.47 ± 22.18 vs. 72.89 ± 19.28, respectively; p < 0.05). The small sample size is a limitation of our study.Conclusions: HRQoL does not appear to be influenced in anogenital wart patients, as measured by the generic instrument SF-36. It is therefore important to develop specific instruments for the measurement of HRQoL in this group of patients. © 2011 Koupidis et al; licensee BioMed Central Ltd.

The factors predicting an unfavourable response of genital warts to treatment have not been determined. The disease characteristics were recorded for 390 patients with genital warts and treated by cryotherapy. The time to achieve clearance was recorded. A personal and family history of asthma, hay fever or eczema, as well as a personal history of common warts and number of recurrences was obtained by telephone four to five years after the clinical visits. In multiple regression analysis, the number of lesions (P < 0.001), extent of the disease (P = 0.003) and personal history of atopy (P = 0.001) were found to influence the time until response to treatment. Similar results were obtained for family history of atopy. The number of sexual partners (P = 0.007), extent of the disease (P = 0.009) and personal history of atopy (P < 0.001) were the main factors influencing the probability of recurrence in multiple logistic regression. The results for family history of atopy were again similar. The study concludes that atopy is a major factor influencing the time frame of the therapeutic response and the probability of recurrence in patients with genital warts.

Background Factors predicting an unfavourable course of genital warts to treatment have not been determined. Materials and methods Behavioural and baseline disease characteristics were recorded from 246 males with anogenital warts. Urethral swabs were obtained and examined using the Hybrid Capture 2 Microplate assay. Patients were treated for their anogenital warts with cryotherapy, imiquimod cream 5% or podophyllotoxin. They were followed up every 3 months for 1 year. Results Patients with a negative or low-risk initial test tended to respond earlier to treatment than those with a high/intermediate-risk human papillomavirus (HPV) or with a dual infection (P = 0.028). The response rate was unrelated (P > 0.05) to the duration, number and anatomical location of the lesions and to the patient's age and sexual orientation, and only marginally to the initial extent of the lesion (P = 0.046). However, the type of treatment predicted a favourable response (P ≤ 0.001), with patients who received both imiquimod and crotherapy responding worse. Considering all factors simultaneously in logistic regression, only the type of treatment and extent of the disease were found to influence the response rate. Conclusion The type of treatment and extent of the disease were the only factors found critical for patients' response. © 2009 European Academy of Dermatology and Venereology.