Declining levels of serum chemokine (C-X-C motif) ligand 10 over time are associated with new onset of psoriatic arthritis in patients with psoriasis: a new biomarker?

BACKGROUND: We previously found that serum levels of chemokine (C-X-C motif) ligand 10 (CXCL10) decreased after the onset of psoriatic arthritis (PsA). OBJECTIVES: We measured CXCL10 levels over time in patients with psoriasis who developed PsA to determine whether the drop in CXCL10 was specific to these patients and further assess its association with PsA development. METHODS: Prospectively followed patients with psoriasis without arthritis [cutaneous psoriasis (PsC)] were assessed yearly by rheumatologists for the presence of PsA. Patients with PsC who developed PsA (converters) were matched to those that did not develop PsA (nonconverters) based on psoriasis duration and the interval between follow-up visits. The duration between baseline and the first visit postconversion in converters was used to assign a pseudoconversion date in nonconverters. Linear mixed-effects models were used to model the expression of CXCL10 over time. RESULTS: CXCL10 significantly declined over time in converters prior to PsA development with a significant difference in the trend over time between converters (n = 29) and nonconverters (n = 52; P < 0·001). CXCL10 continued to decline after PsA onset in a subset of converters. There was a significant difference in the trend of CXCL10 levels between converters (n = 24) and nonconverters (n = 16; P = 0·01) preconversion/pseudoconversion. This difference remained postconversion (P = 0·006) and was not different from the preconversion period (P = 0·75). CONCLUSIONS: A large difference in CXCL10 was identified in patients with PsC that are destined to develop PsA over time. This exploratory analysis supports the association of CXCL10 with PsA development in patients with PsC and warrants further study of the predictive ability of this chemokine. What is already known about this topic? Chemokine (C-X-C motif) ligand 10 (CXCL10) is elevated in psoriatic affected tissues and serum and/or plasma. Patients with psoriasis that develop psoriatic arthritis (PsA) have elevated CXCL10 levels at baseline and these levels drop after arthritis onset. What does this study add? By monitoring levels of CXCL10 in serum over multiple visits in patients with psoriasis that develop PsA as well as those that do not develop PsA, an association was identified between CXCL10 and PsA development. What is the translational message? CXCL10 is a strong candidate for use by physicians for the detection of patients with psoriasis that are at risk of developing PsA. Linked Comment: Kirby and Fitzgerald. Br J Dermatol 2020; 183:805-806.

Systemic inflammation and painful joint burden in osteoarthritis: a matter of sex?

OBJECTIVE: We investigated the association between serum levels of C-reactive protein (CRP) and the extent of multijoint pain among individuals with hip/knee osteoarthritis (OA) and determined whether the association differs by sex. DESIGN: Serum CRP and cartilage oligomeric matrix protein (COMP) were determined by enzyme-linked immunosorbent assay (ELISA) in 189 individuals (101 female, 88 male) scheduled for total hip/knee arthroplasty for OA. Patients indicated on a homunculus all painful joints; a summed count was derived. A series of negative binomial regression models was used to investigate the cross-sectional association between painful joint count (outcome) and serum CRP concentrations, adjusting for age, sex, body mass index (BMI), comorbidity count and COMP. An interaction between sex and these biomarkers was tested. RESULTS: Mean age: 66 among women, 65 among men. Women had higher mean joint count (3.7 vs 2.5, P < 0.01; 4+ joint count reported by 37% women, 25% men). Median CRP concentration was higher in women (15.4 mg/l vs 9.3, P = 0.07). From adjusted analyses, the effects of both ln(CRP) and ln(COMP) were modified by sex (P < 0.05). Increasing ln(CRP) was associated with greater painful joint count among women, but not men. CONCLUSIONS: There may be a dose-response association between painful joint burden in OA and systemic inflammation, and it appears the association is sex-specific, which may in part explain inconsistent findings in the literature. Our results underline the importance of showing sex-specific associations in OA, especially when studying the influence of inflammation.

Lupus - the cold, hard facts.

Systemic lupus erythematosus (SLE) is a multisystem chronic disease with a multitude of clinical presentations. We review and synthesize how an environmental insult (exposure to extreme cold for a short duration) and endogenous (antiphospholipid antibody syndrome, SLE vasculitis) insults in a susceptible young female with lupus (peripheral arterial disease, smoking, SLE) led to a perfect storm resulting in catastrophic injuries (frostbite).

Prevalence and predictors of reduced work productivity in patients with psoriatic arthritis.

OBJECTIVES: Psoriatic arthritis (PsA) is a unique inflammatory musculoskeletal disorder associated with psoriasis. Although high rates of absenteeism have been associated with PsA, less is known about the impact of the disease on the productivity of patients who remain at work. The aim of this study was to identify factors associated with reduced work productivity, as measured by the Work Limitations Questionnaire (WLQ), among patients with PsA. METHODS: Patients attending a single Psoriatic Arthritis Clinic were recruited for participation. Employed participants (including homemakers) first completed a Questionnaire for the Assessment of Work-Related Factors (QAWRF). Eligible participants then completed the WLQ. WLQ scores were used as the dependent variable in linear and logistic regression analyses. Independent variables assessed in this study include work characteristics, demographic factors, and clinical measures. RESULTS: One hundred and eighty-six eligible patients (60.9% males) returned their assessment forms for analysis. The mean reduction in work productivity due to illness was 4.3%. In univariate linear regression analysis, work productivity was significantly associated with sex, education status, Psoriasis Area and Severity Index (PASI), AJC, ESR, Functional Co-morbidity Index (FCI), and support at work; associations with gender, ESR, FCI, and medications were also significant in a reduced multivariate model. CONCLUSIONS: Work productivity was associated with demographic, clinical, and work-related factors in PsA. These variables may be useful in identifying patients who require more aggressive intervention, including the use of effective drugs to control disease activity and advocacy for a more supportive work environment.

Radiological characteristics of the calcaneal spurs in psoriatic arthritis.

OBJECTIVES: Inflammation at the entheses is a distinguishing feature of psoriatic arthritis (PsA). Enthesitis at the heel is the most common location at the Achilles and plantar fascia insertions on the calcaneus. This study aimed to 1) describe the morphological features and measurements of plantar calcaneal spurs in subjects with PsA and controls and 2) determine radiological features that differentiate between inflammatory and non-inflammatory calcaneal spurs. METHODS: Weight bearing lateral foot radiographs of 101 subjects with PsA and 38 control subjects without inflammatory arthritis were examined for plantar calcaneal and Achilles spurs. Three measurements were taken from each radiograph: plantar spur base, mid-segment, and length in millimeters. The differences in radiographic measurements, and the presence of fluffy periostitis of the plantar spurs were then compared between PsA patients and controls. RESULTS: Of the 101 subjects with PsA, 76 (75%) had at least one plantar calcaneal spur and 32 (31.5%) had at least one Achilles tendon spur, compared to 18 (47%) and 3 (8%) respectively in control group (p=0.004). Fluffy plantar periostitis was identified in 14 PsA subjects and none of the controls (p=0.01). The dimensions of plantar spurs were significantly different between groups - longer mid-segment distinguished patients with PsA from controls. CONCLUSIONS: Calcaneal spurs are more common in subjects with PsA than controls. Longer mid-segment measurement was associated with PsA. This study indicates that the presence of fluffy plantar periostitis and broad based and longer mid-segment dimensions are radiological features for inflammatory spurs.

Accuracy of the composite variability index as a measure of the balance between nociception and antinociception during anesthesia.

BACKGROUND: The Composite Variability Index (CVI), derived from the electroencephalogram, was developed to assess the antinociception-nociception balance, whereas the Bispectral Index (BIS) was developed to assess the hypnotic state during anesthesia. We studied the relationships between these indices, level of hypnosis (BIS level), and antinociception (predicted remifentanil effect-site concentrations, CeREMI) before and after stimulation. Also, we measured their association with movement in response to a noxious stimulus. METHODS: We randomized 120 patients to one of 12 groups targeting different hypnotic levels (BIS 70, 50, and 30) and various CeREMI (0, 2, 4, or 6 ng/mL). At pseudo-steady state, baseline values were observed, and a series of stimuli were applied. Changes in BIS, CVI, heart rate (HR), and mean arterial blood pressure (MAP) between baseline and response period were analyzed in relation to level of hypnosis, antinociception, and somatic response to the stimuli. RESULTS: CVI and BIS more accurately correlate with somatic response to an Observer Assessment of Alertness and Sedation-noxious stimulation than HR, MAP, CeREMI, and propofol effect-site concentration (Tukey post hoc tests P < 0.01). Change in CVI is more adequate to monitor response to stimulation than changes in BIS, HR, or MAP (as described by the Mathews Correlation Coefficient with significance level set at P < 0.001). In contrast, none of the candidate analgesic state indices was uniquely related to a specific opioid concentration and is extensively influenced by the hypnotic state as measured by BIS. CONCLUSIONS: CVI appears to correlate with somatic responses to noxious stimuli. However, unstimulated CVI depends more on hypnotic drug effect than on opioid concentration.

Muscle coactivation during gait in children with and without cerebral palsy.

BACKGROUND: Children with Cerebral Palsy (CP) walk with an uncoordinated gait compared to Typically Developing (TD) children. This behavior may reflect greater muscle co-activation in the lower limb; however, findings are inconsistent, and the determinants of this construct are unclear. RESEARCH OBJECTIVES: (i) Compare lower-limb muscle co-activation during gait in children with, and without CP, and (ii) determine the extent to which muscle co-activation is influenced by electromyography normalization procedures and Gross Motor Function Classification System (GMFCS) class. METHODS: An electromyography system measured muscle activity in the rectus femoris, semitendinosus, gastrocnemius, and tibialis anterior muscles during walking in 46 children (19 CP, 27 TD). Muscle co-activation was calculated for the tibialis anterior-gastrocnemius (TA-G), rectus femoris-gastrocnemius (RF-G), and rectus femoris-semitendinosus (RF-S) pairings, both using root mean squared (RMS)-averaged and dynamically normalized data, during stance and swing. Mann-Whitney U and independent t-tests examined differences in muscle co-activation by group (CP vs. TD) and GMFCS class (CP only), while mean difference 95% bootstrapped confidence intervals compared electromyography normalization procedures. RESULTS: Using dynamically normalized data, the CP group had greater muscle co-activation for the TA-G and RF-G pairs during stance (p < 0.01). Using RMS-averaged data, the CP group had greater muscle co-activation for TA-G (stance and swing, p < 0.01), RF-G (stance, p < 0.05), and RF-S (swing, p < 0.01) pairings. Muscle co-activation calculated with dynamically normalized, compared to RMS-averaged data, were larger in the RF-S and RF-G (stance) pairs, but smaller during swing (RF-G). Children with CP classified as GMFCS II had greater muscle co-activation during stance in the TA-G pair (p < 0.05). SIGNIFICANCE: Greater muscle co-activation observed in children with CP during stance may reflect a less robust gait strategy. Although data normalization procedures influence muscle co-activation ratios, this behavior was observed independent of normalization technique.

Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity and network oscillations. It is characterized by neuronal loss, brain atrophy and a decline in cognitive and functional abilities. Cognito's Evoked Gamma Therapy System provides an innovative approach for AD by inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects in experimental AD models. The present study (NCT03556280: OVERTURE) evaluated the feasibly, safety and efficacy of evoked gamma oscillation treatment using Cognito's medical device (CogTx-001) in participants with mild to moderate AD. Methods: The present study was a randomized, double blind, sham-controlled, 6-months clinical trial in participants with mild to moderate AD. The trial enrolled 76 participants, aged 50 or older, who met the clinical criteria for AD with baseline MMSE scores between 14 and 26. Participants were randomly assigned 2:1 to receive self-administered daily, one-hour, therapy, evoking EEG-verified gamma oscillations or sham treatment. The CogTx-001 device was use at home with the help of a care partner, over 6 months. The primary outcome measures were safety, evaluated by physical and neurological exams and monthly assessments of adverse events (AEs) and MRI, and tolerability, measured by device use. Although the trial was not statistically powered to evaluate potential efficacy outcomes, primary and secondary clinical outcome measures included several cognitive and functional endpoints. Results: Total AEs were similar between groups, there were no unexpected serious treatment related AEs, and no serious treatment-emergent AEs that led to study discontinuation. MRI did not show Amyloid-Related Imaging Abnormalities (ARIA) in any study participant. High adherence rates (85-90%) were observed in sham and treatment participants. There was no statistical separation between active and sham arm participants in primary outcome measure of MADCOMS or secondary outcome measure of CDR-SB or ADAS-Cog14. However, some secondary outcome measures including ADCS-ADL, MMSE, and MRI whole brain volume demonstrated reduced progression in active compared to sham treated participants, that achieved nominal significance. Conclusion: Our results demonstrate that 1-h daily treatment with Cognito's Evoked Gamma Therapy System (CogTx-001) was safe and well-tolerated and demonstrated potential clinical benefits in mild to moderate AD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03556280.

The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C.

A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.

Closure of bronchopleural fistula by interventional bronchoscopy using sealants and endobronchial devices.

BACKGROUND: Bronchopleural fistula (BPF) is a communication in the form of a sinus tract between the pleural space and the bronchial tree. Chronic bronchopleural fistula (BPF) is a rare but a serious complication of several pulmonary and postoperative conditions. BPF carries a high morbidity and mortality and is associated with prolonged hospital stay and thus high resource consumption. Till date surgical intervention has been the main stay of management of chronic BPF. Our study was carried out to study the efficacy of sealants like Bioglue, Tissel glue and endobronchial devices like coils to close the BPFs through bronchoscopic interventions in those cases which failed to close with the conventional treatment regimen and progressed to chronicity. METHOD: This study was carried out in a tertiary care hospital. A total 25 patients of chronic BPF/air leaks were selected and subjected to bronchoscopic localization and subsequent intervention using sealants and coils. RESULTS: Total 25 patients with chronic BPF were treated with bronchoscopic interventions using glues, and coils.23 patients were males and 2 were females and 14 were postoperative while 11 patients were non operative. Only smaller fistulas were amenable to glues and coils while there was recurrence in patients with larger air leaks requiring surgical intervention. CONCLUSION: From this study it is concluded that non-operative bronchoscopic interventions to seal the air leaks are effective only in smaller air leaks i.e. alveolopleural fistula (APF). The larger air leaks like leaking stump and larger bronchopleural fistula have not got long lasting and encouraging results with sealants and endobronchial devices.

Prognostic factors for survival in systemic lupus erythematosus associated pulmonary hypertension.

OBJECTIVE: Pulmonary hypertension (PH) is a rare but severe manifestation of systemic lupus erythematosus (SLE) that can ultimately result in death. The identification of factors that prognosticate survival in SLE-PH is necessary for appropriate monitoring, timing of therapeutics and lung transplantation. The primary objective of this study was to identify prognostic factors for survival in SLE-PH through review of the literature. The methodological quality of the prognostic studies was also evaluated. METHODS: A systematic review of the literature was performed to identify studies evaluating prognostic factors for survival in SLE-PH. Medline, EMBASE, CINAHL, and Cochrane Central Registry of Controlled Trials (inception - week 2 2010) were searched. A standardized abstraction form was used by two independent reviewers to extract prognostic factors. Methodological quality was evaluated using a validated quality index. RESULTS: Twenty-three observational studies from 375 citations were evaluated. Elevated mean pulmonary artery pressure, Raynaud's phenomenon, thrombocytopenia, plexiform lesion, infection, thrombosis, pregnancy, pulmonary vasculitis and anticardiolipin antibodies were associated with decreased survival. Lupus disease activity, nephritis and central nervous system disease were not associated with survival. The sample sizes were small and methodological quality of the studies was variable. CONCLUSION: This study summarizes factors that may be associated with decreased survival in SLE-PH. The small sample sizes and variable methodological quality preclude definitive conclusions. This study provides the groundwork for further research using large cohorts.

Non-motor features in essential tremor.

INTRODUCTION: Essential tremor (ET) is increasingly recognized to have several non-motor manifestations. The aim of this study was to determine the prevalence of non-motor manifestations in ET and its impact on the quality of life (QOL). METHODS: This was a cross-sectional case-control questionnaire-based study. The subjects were 50 patients with ET and 50 matched healthy controls. All subjects were assessed by Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Parkinson Fatigue Scale, Brief Pain Inventory, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. In addition, QOL in Essential Tremor questionnaire was administered to patients with ET. RESULTS: Patients with ET, when compared with controls, had significantly higher prevalence and higher mean scores of sleep disturbances (46% vs 8%, P < 0.001; 5.9 ± 4.6 vs 2.6 ± 2.3, P < 0.001), fatigue (30% vs 8%, P = 0.009; 5.8 ± 0.8 vs 2.5 ± 0.4, P < 0.001), anxiety (66% vs 18%, P = 0.009; 7.4 ± 9.0 vs 0.7 ± 2.6, P < 0.001), depression (44% vs 8%, P = 0.009; 7.8 ± 7.9 vs 1.7 ± 3.3, P < 0.001) as well as higher mean score of pain severity (1.9 ± 2.3 vs 0.6 ± 1.2, P = 0.001) and interference owing to pain (2.0 ± 2.9 vs 0.5 ± 1.2, P = 0.001). Following hierarchical regression analysis, depression was the only non-motor feature that affected the QOL. CONCLUSION: There was a significantly higher prevalence and greater severity of sleep disturbances, fatigue, pain, anxiety, and depression in patients with ET and depression significantly affected the QOL.

Increases in electroencephalogram and electromyogram variability are associated with an increased incidence of intraoperative somatic response.

BACKGROUND: sBIS, the variability of the Bispectral Index (BIS), sEMG, the variability of facial electromyogram power (EMG), and the Composite Variability Index (CVI) are 3 new measures of electroencephalogram and EMG variability. CVI is a single measure of the combined variability in BIS and EMG. We investigated whether increases in these variables are associated with intraoperative somatic responses. METHODS: This multicenter study included 120 patients undergoing elective, noncardiac surgery from 4 different sites. General anesthesia was maintained using propofol and remifentanil at 2 of the sites and sevoflurane and remifentanil at the 2 other sites. Propofol or sevoflurane was adjusted to maintain BIS between 45 and 60. Clinicians were blinded to CVI (v2.0) at all times, and remifentanil infusions were adjusted at the discretion of the clinician. The times of all intraoperative somatic events, defined as movement, grimacing, or eye opening, were recorded. Offline, the maintenance phase of each case was divided into consecutive, nonoverlapping, 10-minute segments. Segments were identified as containing a somatic event or containing no events. For each segment, mean sBIS, sEMG, and CVI and the heart rate (HR) range and mean arterial blood pressure range were calculated. To quantify how effectively each variable discriminated between somatic event segments and nonevent segments, we computed the area under the receiver operating characteristic (ROC) curve for each variable. Finally, we observed the time course of sBIS, sEMG, CVI, and the HR range before each somatic event and characterized the earliest time before the somatic event at which each variable was able to discriminate between the somatic events and a specified set of nonevents. RESULTS: The analysis included 33 somatic event segments and 829 nonevent segments from 105 surgical cases. The areas under the ROC curve (±SE) for sBIS, sEMG, and CVI were 0.83 ± 0.04, 0.92 ± 0.02, and 0.89 ± 0.03, respectively. The areas under the ROC curve for HR range and mean arterial blood pressure range were 0.77 ± 0.03 and 0.68 ± 0.05, respectively. CVI, sBIS, and sEMG all demonstrated higher average values before upcoming somatic events when compared with nonevents. HR range only showed a difference within a few seconds before the somatic event. CONCLUSION: sBIS, sEMG, and CVI, measures of electroencephalogram and EMG variability, increased when intraoperative somatic events occurred. sBIS, sEMG, and CVI discriminated between 10-minute segments that contained a somatic event and those segments that did not contain an event better than changes in HR and mean arterial blood pressure. Furthermore, CVI increases before somatic events began earlier than HR changes and may provide caregivers with an early warning of potentially inadequate antinociception.

Differential major histocompatibility complex class I chain-related A allele associations with skin and joint manifestations of psoriatic disease.

About 30% of patients with psoriasis have psoriatic arthritis (PsA), an inflammatory arthritis that can affect both axial and peripheral joints. Major histocompatibility complex class I chain-related A (MICA) alleles have previously been shown to be associated with PsA; however it is unclear whether there is a differential association of MICA alleles with skin and joint manifestations of PsA. Here, we describe a case-control study that aims to validate previously reported MICA allele associations with PsA and determine whether MICA alleles differentiate patients with PsA from those with psoriasis without PsA. Two hundred forty-nine unrelated Caucasian PsA patients, 243 psoriasis patients without arthritis, and 248 healthy controls were genotyped for 55 MICA alleles using PCR-SSP, and for human leucocyte antigen (HLA)-B and HLA-C alleles by PCR-SSO reverse line blot. Allele frequencies were calculated and logistic regressions were performed, adjusting for HLA-B and HLA-C alleles previously shown to be associated with psoriasis and/or PsA. Several MICA alleles were associated with psoriatic disease, PsA, and psoriasis compared with controls, and PsA compared with psoriasis in univariate analyses. Haplotype analysis showed evidence of strong linkage disequilibrium (LD) between PsA and psoriasis risk alleles of HLA-C, HLA-B, and MICA. After adjusting for significant HLA-B and HLA-C alleles in multivariate analyses, MICA*016 remained significantly associated with psoriasis [odds ratio (OR) = 5.5, P = 0.008]. MICA*00801 homozygosity was associated with susceptibility to PsA when compared with patients with psoriasis alone (OR = 2.26, P = 0.009). We conclude that most MICA allele associations with psoriasis and PsA are dependent on LD with HLA-B and HLA-C risk alleles. Independent of HLA, only MICA*016 influences the risk of developing psoriasis without arthritis, and homozygosity for MICA*00801 increases the risk of developing PsA in patients with psoriasis.

Outcome after autologous dermal sling-assisted immediate breast reconstruction.

BACKGROUND: In selected patients undergoing mastectomy and immediate reconstruction, a de-epithelialized skin flap (dermal sling) may be used to complete the submuscular pocket. This study examined the safety and efficacy of an autologous dermal sling in providing inferolateral support to the implant or tissue expander during immediate breast reconstruction. METHODS: Patients were identified from an electronic prospective database. Records of all patients were reviewed for details of management, complications and follow-up. Patient satisfaction and quality of life in the postoperative period were determined using the BREAST-Q(©) questionnaire. RESULTS: Between October 2008 and August 2010, 21 patients underwent 28 dermal sling-assisted breast reconstruction procedures. Their median age was 48 (range 30-70) years. Median hospital stay was 5 (range 3-7) days. Drains were removed at a median of 5 (range 3-7) days after surgery. During the operation a median volume of 150 ml was added to the tissue expander. The most common postoperative complication was superficial -junction breakdown in five patients, followed by seroma and infection each in three patients, but no implant required removal. BREAST-Q(©) responses indicated a high level of satisfaction overall with the reconstructed breast. CONCLUSION: Dermal sling-assisted immediate breast reconstruction has a low serious complication rate, provides stable soft tissue cover for the tissue expander and is associated with a high level of patient satisfaction. A larger pocket can be created, permitting more fluid to be added to the expander.

Predictors of parenting stress in mothers of children with spina bifida.

STUDY DESIGN: Prospective cross-sectional multidimensional study using clinical assessment and standard measures. OBJECTIVES: To determine the medical and social factors associated with parenting stress among mothers of children with spina bifida. SETTING: Spina bifida clinics of two tertiary hospitals in urban Kuala Lumpur, Malaysia. METHODS: A total of 81 mothers of children aged 1-18 years completed the Parenting Stress Index-Short Form (PSI/SF). Each child's adaptive skills were assessed using the Vineland Adaptive Behaviour Scales (VABS), Interview Edition. Medical and social data were obtained from direct interviews and case note reviews. Hierarchical multiple regression analysis was used to investigate factors that were determinants for high scores in the parental distress (PD), difficult child (DC) and parent-child dysfunctional interaction (P-CDI) subdomains of the PSI/SF. Results were expressed as beta coefficient (ß) and 95% confidence intervals (95% CIs). RESULTS: Single-parent families (ß 8.6, 95% CI 3.4-13.9) and the need for clean intermittent catheterization of bladder (ß 3.5, 95% CI 0.7-6.2) were associated with high PD scores. Clean intermittent catheterization (ß 3.0, 95% CI 0.5-5.5) was associated with higher DC scores. Lower composite VABS scores (ß -0.08, 95% CI -0.02 to -0.15) and mother as the sole caregiver (ß 2.6, 95% CI 0.15-4.96) was associated with higher P-CDI scores. CONCLUSION: The need for clean intermittent catheterization was the only medical factor associated with parenting stress in mothers of children with spina bifida. This was mediated by single parenthood, caregiver status and the child's adaptive skills.

Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).

OBJECTIVE: To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS). METHODS: The ToPAS was developed through review of items seen in patients with PsA and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models. RESULTS: In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%. CONCLUSION: Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.

Familial aggregation of psoriatic arthritis.

OBJECTIVES: The aim of this study was to determine the recurrence risk of psoriatic arthritis (PsA) and uncomplicated psoriasis in first-degree relatives (FDRs) of patients with PsA. METHODS: All available FDRs (full siblings, parents and children) of 100 consecutive consenting patients attending a PsA clinic were evaluated for the presence of psoriasis and PsA using a standard protocol. The protocol included a screening questionnaire, physical examination by a rheumatologist, and radiographic and laboratory assessment. The prevalence of PsA and psoriasis in FDRs of the index cases was determined, and the recurrence risk ratio (lambda) was calculated, assuming a population prevalence of PsA of 0.25%, and a population prevalence of psoriasis of 2%. RESULTS: The 100 probands had 533 relatives. Eighty-four of them were deceased and 53 were unavailable (age <16 years). Of the remaining 396 FDRs, 107 did not participate (living too far away/did not consent). Thus, 289/396 (73%) of the available FDRs participated in the study. There were 130 siblings, 108 parents and 51 children. The prevalence of PsA and psoriasis among FDRs was 7.6% and 15.2%, respectively. The lambda(1 )was 30.4 for PsA and 7.6 for psoriasis. The prevalence of PsA and psoriasis in siblings was 7.7% and 17.7%, respectively. The lambda(S) was 30.8 for PsA and 8.8 for psoriasis. CONCLUSIONS: The recurrence risk ratio for both PsA and psoriasis is high in FDRs and siblings of patients with PsA. These results confirm that both PsA and psoriasis have a strong heritable component.

From ankylosis to pencil-in-cup deformity in psoriatic arthritis: a case report.

A 56-year-old woman with psoriatic arthritis is presented whose initially ankylosed digit was later found to develop pencil-in-cup change. The patient was treated over that period with etanercept and had no signs of active arthritis. The possible mechanisms for these changes are discussed.

Automatic identification of epileptic electroencephalography signals using higher-order spectra.

Epilepsy is a pathological condition characterized by the spontaneous and unforeseeable occurrence of seizures, during which the perception or behaviour of patients is disturbed. An automatic early detection of the seizure onsets would help the patients and observers to take appropriate precautions. Various methods have been proposed to predict the onset of seizures based on electroencephalography (EEG) recordings. The use of non-linear features motivated by the higher-order spectra (HOS) has been reported to be a promising approach to differentiate between normal, background (pre-ictal), and epileptic EEG signals. In this work, these features are used to train both a Gaussian mixture model classifier and a support vector machine classifier. Results show that the classifiers were able to achieve 93.11 per cent and 92.67 per cent classification accuracy respectively, with selected HOS-based features. About 2 h of EEG recordings from ten patients were used in this study.