Pregnancy and perinatal outcomes of early vs late selective termination in dichorionic twin pregnancy: systematic review and meta-analysis.

OBJECTIVE: To evaluate outcomes of dichorionic twin pregnancies undergoing early vs late selective termination of pregnancy (ST). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to March 2022. The primary outcome of this study was pregnancy loss prior to 24 weeks' gestation. The secondary outcomes included preterm birth (PTB) before 37, 34, and 32 weeks, preterm prelabor rupture of membranes (PPROM), gestational age (GA) at delivery, Cesarean delivery, mean birth weight, 5-min Apgar score < 7, overall neonatal morbidity and neonatal survival. Only prospective or retrospective studies reporting data on the outcome of early (before 18 weeks) vs late (at or after 18 weeks) ST in dichorionic twin pregnancies were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale for cohort studies. Random-effects head-to-head meta-analysis was used to analyze the data. RESULTS: Seven studies reporting on 649 dichorionic twin pregnancies were included in this systematic review. The risk of pregnancy loss prior to 24 weeks was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST (1% vs 8%; odds ratio (OR), 0.25 (95% CI, 0.10-0.65); P = 0.004). The risk of PTB was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST when considering PTB before 37 weeks (19% vs 45%; OR, 0.36 (95% CI, 0.23-0.57); P < 0.00001), before 34 weeks (4% vs 19%; OR, 0.24 (95% CI, 0.11-0.54); P = 0.0005) and before 32 weeks (4% vs 20%; OR, 0.21 (95% CI, 0.05-0.85); P = 0.03). The mean birth weight was significantly greater in the early-ST group (mean difference (MD), 392.2 g (95% CI, 59.1-726.7 g); P = 0.02), as was the mean GA at delivery (MD, 2.47 weeks (95% CI, 0.04-4.91 weeks); P = 0.049). There was no significant difference between dichorionic twin pregnancies undergoing early compared with late ST in terms of PPROM (P = 0.27), Cesarean delivery (P = 0.38), 5-min Apgar score < 7 (P = 0.35) and neonatal survival of the non-reduced twin (P = 0.54). CONCLUSIONS: The risk of pregnancy loss prior to 24 weeks and the rate of PTB before 37, 34 and 32 weeks were significantly higher in dichorionic twin pregnancies undergoing late vs early ST, thus highlighting the importance of early diagnosis of fetal anomalies in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Preoperative MRI for oral tongue squamous cell carcinoma: timing and correlation to histopathology.

Magnetic resonance imaging (MRI) is an integral part of the evaluation of local and regional disease in tongue squamous cell carcinoma prior to surgery. The aim of this study was to evaluate the accuracy of MRI in assessing tumour dimensions, as well as the impact of the time-lag from diagnostic biopsy on the accuracy of MRI. The medical records of 64 patients with tongue carcinoma were reviewed retrospectively. Tumour maximum diameter and tumour depth of invasion were compared between pathology and MRI (T1- and T2-weighted). MRI-derived maximum tumour diameter and depth of invasion correlated strongly with histopathology: T1-weighted (r = 0.700 and r = 0.813, respectively) and T2-weighted (r = 0.734 and r = 0.834, respectively). A significant correlation was found between measurements on T1 and T2 MRI for both parameters (P = 0.955 and P = 0.984, respectively). The accuracy rate of MRI for T-staging of early tumours was low: 10% for T1 tumours; 39.3% for T2 tumours. A time-lag of less than 2 weeks between the diagnostic biopsy and MRI adversely affected the correlation of tumour dimensions. MRI is a reliable tool for evaluating tongue carcinoma; however, it overestimates early tumours. A 2-week delay after diagnostic biopsy is desired before completing an MRI. Alternatively, if logistics allow, a pre-biopsy MRI is preferred, especially for T1-T2 tumours.

Exposure to extrinsic stressors, social defeat or bisphenol A, eliminates sex differences in DNA methyltransferase expression in the amygdala.

Chemical and psychological stressors can exert long lasting changes in brain function and behaviour. Changes in DNA methylation have been shown to be an important mechanism mediating long lasting changes in neural function and behaviour, especially for anxiety-like or stress responses. In the present study, we examined the effects of either a social or chemical stressor on DNA methyltransferase (DNMT) gene expression in the amygdala, an important brain region modulating stress responses and anxiety. In adult California mice (Peromyscus californicus) that were naïve to social defeat, females had higher levels of Dnmt1 expression in punch samples of the central amygdala (CeA) than males. In addition, mice that underwent social defeat stress showed reduced Dnmt1 and Dnmt3a expression in the CeA of females but not males. A second study using more anatomically specific punch samples replicated these effects for Dnmt1. Perinatal exposure (spanning from periconception through lactation) to bisphenol A or ethinyl oestradiol (oestrogens in birth control pills) also abolished sex differences in Dnmt1 expression in the CeA but not the basolateral amygdala. These findings identify a robust sex difference in Dnmt1 expression in the CeA that is sensitive to both psychological and chemical stressors. Future studies should aim to examine the impact of psychological and chemical stressors on DNA methylation in the CeA and also investigate whether Dnmt1 may have an underappreciated role in plasticity in behaviour.

Temporomandibular joint involvement in patients with multiple myeloma-a retrospective study.

Multiple myeloma (MM) is a common hematological malignancy that has widespread manifestations in multiple organs, including bones and joints. This retrospective study aimed to evaluate the involvement of the temporomandibular joint (TMJ) in patients with MM. Consecutive subjects with a diagnosis of MM who presented to the oral and maxillofacial surgery clinic for routine evaluation between 2008 and 2014 were identified. Patients who had a computed tomography (CT) scan of the TMJs as part of their MM staging were included in the study. Outcome variables were the presence of TMJ myelomatous changes on CT and the presence of TMJ symptoms. Of the 88 patients included in the study, 28 demonstrated TMJ myelomatous lesions on CT scans and 10 patients complained of TMJ pain or dysfunction. The CT scans of seven of the 10 symptomatic patients demonstrated myelomatous involvement of the TMJ area. Myelomatous involvement of the TMJ is common in MM patients and the majority of lesions are asymptomatic. An MM patient complaining of temporomandibular symptoms is relatively highly likely to having a lesion in the TMJ. Diagnosing the myelomatous lesions in the TMJ is important for accurate hemato-oncologic staging and providing treatment without delay.

Gene Targeting Studies of Hyperexcitability and Affective States of Alcohol Withdrawal in Rodents.

Genetically engineered rodents can be used to examine the influence of single genes on alcoholism-related phenotypes. We review studies that employed gene targeting with a focus on ethanol withdrawal-associated behaviors. Earlier studies targeted the glutamate and GABA systems as contributors to the underlying hyperexcitable state of convulsions or similar signs of ethanol withdrawal. Over the past decade, many gene-targeting studies have continued to focus on the glutamatergic and GABAergic systems; however, an increasing number of these studies have focused on other withdrawal outcomes such as anxiety-like behavior and escalated ethanol consumption. Although negative affective states may drive escalated ethanol drinking, few reported studies examined the phenotypes together. However, there is significant overlap in the systems that were manipulated in relation to studying the phenotypes individually. These studies reveal common genetic influences on withdrawal-associated anxiety, convulsions, and escalated drinking that may contribute to relapse, setting the stage for the identification of novel medications to jointly target these effects.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

A prospective cohort study to determine the relationship between serum infliximab concentration and efficacy in patients with luminal Crohn's disease.

BACKGROUND: Patients with Crohn's disease (CD) may experience disease relapse on maintenance infliximab. Anti-drug antibodies likely contribute to loss of response, and serum infliximab levels likely correlate with efficacy. AIM: To prospectively evaluate the relationship between trough serum infliximab concentration and disease activity. METHODS: Adult patients (N = 327) with a diagnosis of CD who had received at least five consecutive infliximab infusions and who planned to receive at least two additional infusions were enrolled. The Crohn's Disease Activity Index (CDAI), serum infliximab, C-reactive protein (CRP) and antibodies-to-infliximab (ATI) were assessed at baseline, week 4 and week 8. Receiver operating characteristic (ROC) analysis examined the relationship between infliximab concentrations and disease activity. RESULTS: The mean CDAI score, which decreased 1.05 points between infusions, did not correlate with the mean change in trough infliximab concentration (+0.39 µg/mL; r = 0.099, P = 0.083), but was associated with the mean change in CRP concentration (r = 0.19, P < 0.001). Trough infliximab concentrations below 2.8-4.6 µg/mL best predicted a ≥ 70 point increase in the CDAI between infusions, and those below 2.7-2.8 µg/mL best predicted CRP >5 mg/mL at the second infusion. ATI at either visit decreased the proportion of patients with therapeutic infliximab trough levels compared with patients who were ATI negative (17.5% vs. 77.3% at visit 1 and 13.8% vs. 75.6% at visit 3; P < 0.001 for both comparisons). CONCLUSIONS: This prospective study confirms the relationship between trough infliximab concentrations, inflammation and antibodies-to-infliximab. Infliximab trough concentrations below 3 µg/mL may increase the likelihood of symptoms and inflammation (ClinicalTrials.gov identifier: NCT00676988).

Review article: a clinician's guide for therapeutic drug monitoring of infliximab in inflammatory bowel disease.

BACKGROUND: Tumour necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. AIM: The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed. METHODS: The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies-to-infliximab. RESULTS: Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long-term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence-based manner and are probably not cost-effective. Multiple TDM-based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy. CONCLUSIONS: Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomised controlled trials.

Is it all in the family? The effects of early social structure on neural-behavioral systems of prairie voles (Microtus ochrogaster).

The transition to parenthood is generally associated with a reduction in anxiety or anxiety-like behavior across a wide range of species. In some species, juveniles provide supplementary parental care for younger siblings, a behavior known as alloparenting. Although the fitness consequences of alloparenting behavior have been a focus of evolutionary research, less is known about how alloparenting behavior impacts affective states. In the socially monogamous prairie vole (Microtus ochrogaster), most juveniles exhibit alloparenting behavior, making the species an ideal model for examining the effects of alloparenting on future behavioral outcomes. We randomly assigned juvenile voles to alloparenting (AL) or no alloparenting (NoAL) groups and behaviorally phenotyped them for anxiety-like and social behaviors using the elevated plus maze (EPM), open field test (OFT), startle box, social interaction test, juvenile affiliation test, and partner preference test. AL voles displayed more anxiety-like and less exploratory behaviors than NoAL voles, spending significantly less time in the open arms of the EPM and center of an open field. We dissected the CA1 region of the hippocampus and the bed nucleus of the stria terminalis (BNST) from brains of behaviorally phenotyped voles and nontested siblings as well. Decreased brain-derived neurotrophic factor (BDNF) expression in CA1 has generally been associated with increased anxiety-like behavior in other rodents, while an anxiogenic role for BDNF in BNST is less established. Western blot analyses showed that alloparenting experience increased expression of BDNF in the BNST but decreased BDNF expression in the CA1 region of hippocampus (CA1) of nontested voles. There were similar differences in BNST BDNF of behaviorally phenotyped voles, and BDNF levels within this region were negatively correlated with exploratory behavior (i.e. time in center of OFT). Our results suggest that BDNF signaling in BNST and CA1 fluctuate with alloparenting experience, and they contribute to an increasingly complex "BDNF hypothesis" in which behavioral effects of this molecule are region-specific.

Relationship between social support and autonomic function during a stress protocol in ulcerative colitis patients in remission.

BACKGROUND: The relationship of psychological stress to relapse in ulcerative colitis (UC) is inconsistent. This may be due to a failure to identify patient characteristics, such as social support, which moderate the transduction of stress from the central nervous system to the immune system. In this study we tested the hypothesis that social support enhances parasympathetic modulation of heart rate in UC. METHODS: An indirect measure of autonomic function (heart rate variability; HRV) was measured in 108 patients with UC in remission during a standard protocol involving periods of stress, paced breathing, and relaxation. Social support was measured with the Social Support Questionnaire. RESULTS: After controlling for age, which is strongly related to HRV, both satisfaction with social support (F = 5.7, significance = 0.002) and its interaction with age (F = 7.8, significance <0.001) were associated with high-frequency HRV, which measures parasympathetic modulation of heart rate. Social support was associated with higher levels of high-frequency HRV at almost all points in the stress protocol. Neither age nor social support was associated with differences in the LF/HF ratio, which measures sympathetic modulation of heart rate. CONCLUSIONS: Social support is related to parasympathetic activity in UC. Given previous evidence of an antiinflammatory role for the parasympathetic nervous system, this suggests that autonomic function could serve as a mediating link between social support and reduced inflammatory activity.

Use of ViaBahn open revascularisation technique for above-knee femoro-popliteal anastomosis: a technical note.

We describe a ViaBahn Open Revascularization TEChnique (VORTEC) application in peripheral femoro-popliteal polytetrafluoroethylene (PTFE) graft bypass in 13 patients.

A new minimally invasive hybrid technique for femoro - above knee popliteal bypass.

Femoro above knee popliteal bypass using synthetic graft is a well recognized revascularization procedure in patients with severe lower limb ischemia with either critical limb ischemia (CLI), limiting claudication (IC) or with acute limb ischemia (ALI).Occasionally the patient's general condition would mandate a short and minimally invasive procedure. When endovascular revascularization is not possible or fails then the peripheral VORTEC technique is used. A telescopic sutureless anastomosis is created between an ePTFE graft to the above knee popliteal artery with a bridging piece of VIABHAN. The technique was described in detail and has been published in the August 2011 issue of the EJVES. Between April 2010 and October 2011 seventeen procedures were accomplished successfully in 16 patients. The median follow up was 13 months (range 3-17). Two patients died during follow up from unrelated caused, both from acute cardiac events and both with patent bypasses, one and 5 months after the index operation. There were 2 occasions of limb loss but only one graft loss related amputation. There were 4 thrombectomies for graft occlusions. All four did not have a distal anastomotic stenosis that could predict graft failure on pre occlusion follow up duplex scans. Primary patency for the whole cohort was 65%, the primary assisted patency was 70% and the secondary patency was 85%. In conclusion we believe that this technique could be advantageous in morbid patients and we therefore recommend using it in high risk patients if no endovascular option or saphenous vein are available.

Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis.

BACKGROUND AND AIMS: Antibodies to infliximab reduce serum infliximab with loss of clinical benefit, but undetectable trough serum concentrations of infliximab may occur without antibody formation. The relationship between trough serum infliximab and clinical outcomes was evaluated in acute ulcerative colitis. METHODS: In a cohort of 115 patients with ulcerative colitis treated with three-dose induction followed by scheduled maintenance infliximab, rates of clinical remission, colectomy, antibodies to infliximab and trough serum infliximab were determined. RESULTS: Rates of remission were 32% at week 10 and 37% at week 54. Colectomy occurred in 40% of patients, at a median of 5.3 (IQR 1.9-12.1) months. Detectable trough serum infliximab was present in 39% of patients and, among patients with undetectable infliximab, 41% were antibody positive and 20% were antibody negative. For antibody-positive and antibody-negative patients, rates of remission (18% vs 14%), endoscopic improvement (25% vs 35%) and colectomy (52% vs 59%) were not different. A detectable serum infliximab was associated with higher rates of remission (69% vs 15%; p<0.001) and endoscopic improvement (76% vs 28%, p<0.001). An undetectable serum infliximab predicted an increased risk for colectomy (55% vs 7%, OR 9.3; 95% CI 2.9 to 29.9; p<0.001). Concurrent immunosuppression was not associated with clinical outcomes. CONCLUSIONS: For patients with ulcerative colitis treated with infliximab, a detectable trough serum infliximab predicts clinical remission, endoscopic improvement and a lower risk for colectomy. An undetectable trough serum infliximab, irrespective of antibody status, is associated with less favourable outcomes.

Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging.

AIM: To determine in vivo whether the lateral geniculate nucleus (LGN) undergoes atrophy in patients with glaucoma and vision loss compared with normal subjects. METHODS: Following institutional St Michael's Hospital Research Ethics Board approval, a prospective and masked neuroimaging study was conducted on glaucoma patients with visual-field defects affecting both eyes (n = 10) and age-matched controls (n = 8). Following informed consent, all subjects underwent 1.5-Tesla MRI. Coronal proton density magnetic resonance images of both LGNs were obtained, and LGN height measurements were measured by consensus by three neuroradiologists masked to the diagnosis. Glaucoma and control groups were compared using the t test. RESULTS: Both LGNs were identified and visualised by 1.5-Tesla MRI for every subject. Compared with controls, the mean LGN heights in glaucoma were decreased in right (4.09 (0.89) mm vs 4.74 (0.54) mm, p>0.05) and left LGNs (3.98 (0.57) mm vs 4.83 (0.95) mm; p = 0.033). The combined right and left LGN height in glaucoma was significantly decreased compared with controls (8.07 (1.06) mm vs 9.56 (0.86) mm; p = 0.005). CONCLUSION: In vivo MRI evidence of LGN degeneration in human glaucoma is consistent with ex vivo primate and human neuropathological studies. LGN atrophy may be a relevant biomarker of visual system injury and/or progression in some glaucoma patients.

Review and clinical perspectives for the use of infliximab in ulcerative colitis.

Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn's disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC) differs from that of Crohn's disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members' clinical experiences.

The impact of ulcerative colitis is greater in unmarried and young patients.

GOALS: To determine whether the perceived impact of ulcerative colitis (UC) on activities of living (illness intrusiveness) is greater for people who are not living in a married or common-law relationship. BACKGROUND: In general, social and occupational achievement is not greatly impaired by UC, yet patients, especially young adults, often have interpersonal concerns. METHODS: One hundred fifty-five outpatients with UC were assessed for disease activity, and completed self-reports of marital status, income, social support and illness intrusiveness. RESULTS: Fifty-one patients (32.9%) were single, separated or divorced, and 104 patients (67.1%) were married or in common-law relationships. Compared with those who were married or in common-law relationships, single or separated patients were younger, had a lower household income, had lived with UC for fewer years and were less satisfied with social support. Among 135 patients in remission, marital status was significantly associated with illness intrusiveness, controlling for age, income and perceived social support (F=5.73; P=0.02). Low social support (F=4.94; P=0.03) and younger age (F=7.24; P=0.008) were independently associated with illness intrusiveness. Single patients in remission reported illness intrusiveness of similar severity to that reported by patients with active disease. CONCLUSIONS: The perceived impact of UC on the lives of patients is greater in those who are not married or living in common-law relationships. Youth, single status and lower social support commonly coexist, and exert additive effects on the functional impact of UC. Resources to improve social support should be directed toward this group of patients.

Eruptive tufted angiomas in a patient with Crohn's disease.

Angioblastoma is a rare, benign vascular tumour composed of undifferentiated mesenchymal cells with a tendency to form lumina. This entity was first described by Nakagawa in 1949 as angioblastoma, and Wilson Jones was the first to use the term "tufted angioma" in 1976. Tufted angiomas usually occur in infancy and spread slowly. This report describes lesions from the right side of the forehead, forearms, and thighs of a 24 year old man with a four year history of Crohn's disease, who was receiving infliximab in addition to long standing azathioprine and ciprofloxacillin. He developed numerous small itchy erythematous vascular appearing papules, which on histological examination resembled tufted angiomas, showing the classic "cannon ball" appearance. The lesions regressed within three months. This case may represent an eruptive acquired tufted angioma in which immunosuppression or drug induced modification of angiogenesis played a role in its development and regression. One previous case of eruptive tufted angioma has been reported in an immunosuppressed patient.

Preserving the left arm vein in cases of hemodialysis access generating left internal mammary artery steal syndrome.

In patients undergoing chronic hemodialysis (HD) through an arm arteriovenous fistula (AVF), coronary insufficiency can occur if the patient undergoes a coronary artery bypass graft (CABG) using the ipsilateral internal mammary artery (1-4). Therefore, the creation of a new AVF after CABG should avoid using the arm ipsilateral to the side where the internal thoracic artery was used. In cases where coronary syndrome appears when this advice is not followed, treatment should be offered aimed at overcoming the hemodynamic interference between the diminished coronary supply through the left or right internal mammary artery by closure of the existing fistula, with or without temporary central venous line insertion until the maturation of a new fistula. We suggest a different approach by moving only the arterial inflow site of the AVF to the controlateral subclavian artery, but in addition, leaving the well functioning venous outflow tract intact. In cases of left internal mammary steal it is achieved by creating a conduit running from the right subclavian artery to the left cephalic vein; therefore, creating a new arterial inflow source, connected to the existing functioning old venous outflow tract to maintain an immediately functioning new fistula without a coronary steal.

Diagnostic misclassification reduces the ability to detect linkage in inflammatory bowel disease genetic studies.

BACKGROUND: Linkage data have now identified several inflammatory bowel disease (IBD) susceptibility loci but these data have not been consistently replicated in independent studies. One potential explanation for this is the possibility that patients enrolled in such studies may have been erroneously classified with respect to their diagnosis. AIMS: To determine the rate and type of misclassification in a large population of individuals referred for participation in an IBD genetics study and to examine the effect of diagnostic misclassification on the power to detect linkage. METHODS: The medical records of 1096 patients entered into an IBD genetics programme were reviewed using standardised diagnostic criteria. The original patient reported diagnoses were changed, if necessary, based on review, and the reasons for the change in diagnosis were recorded. To evaluate the effect of misclassification on linkage results, simulations were created with Gensim and analysed using Genehunter to evaluate a model for IBD inheritance. RESULTS: Sixty eight of 1096 (6.2%) individuals had a change in diagnosis from that originally reported. The majority of changes were patients with either Crohn's disease or ulcerative colitis who were determined not to have IBD at all. The principal reasons for changes to the original diagnosis were discordance between the patients' subjective reports of diagnosis and actual clinical history, endoscopic, or pathological results; a change in disease pattern over time; and insufficient information available to confirm the original diagnosis. A 10% misclassification rate resulted in 28.4% and 40.2% loss of power to detect a true linkage when using a statistical model for a presumed IBD locus with lambda(s) values of 1.8 and 1.3, respectively. CONCLUSIONS: Diagnostic misclassification occurs in patients enrolled in IBD genetic studies and frequently involves assigning the diagnosis of IBD to non-affected individuals. Even low rates of diagnostic misclassification can lead to significant loss of power to detect a true linkage, particularly for loci with modest effects as are likely to be found in IBD.

Pediatric migraine prophylaxis with divalproex.

We followed 23 patients with pediatric migraine, ranging in age from 7 to 17 years, who were treated with preventive divalproex sodium for migraine prophylaxis. Patients were evaluated for the presence or absence of comorbid psychiatric disorders or epilepsy to assess the possible differential effects of divalproex therapy. Doses ranged from 3.1 to 32.9 mg/kg/day. Seven patients had comorbid psychiatric disorders, whereas six patients had epilepsy (three rolandic, two generalized, and one indeterminate). Fifteen patients had a greater than 50% reduction in migraine; six patients became headache free. Divalproex doses used were not statistically different among the three groups. A favorable response and headache freedom were more likely in patients with migraine alone or with comorbid epilepsy, and less likely in patients with psychiatric comorbidity. Divalproex was well tolerated, and no significant side effects were reported. No notable changes were noted in behavioral problems, and patients with epilepsy were well controlled. In our cohort of patients, divalproex was most effective in patients with migraine alone or comorbid epilepsy.