Validating the International Classification of Functioning, Disability and Health Comprehensive Core Set for Rheumatoid Arthritis from the patient perspective: a qualitative study

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for Rheumatoid Arthritis (RA) from the patient perspective. METHODS: Patients with RA were interviewed about their problems in daily functioning. Interviews were tape recorded and transcribed verbatim. Interview texts were divided into meaning units. The concepts contained in these meaning units were linked to the ICF according to 10 established linking rules. Of the transcribed data, 15% were analyzed and linked by a second health professional. The degree of agreement was calculated using the kappa statistic. RESULTS: Twenty-one patients were interviewed. Two hundred twenty different concepts contained in 367 meaning units were identified in the qualitative analysis of the interviews and linked to 109 second-level ICF categories. Of the 76 second-level categories from the ICF RA Core Set, 63 (83%) were also found in the interviews. Twenty-five second-level categories, which are not part of the current ICF RA Core Set, were identified in the interviews. The result of the kappa statistic for agreement was 0.62 (95% boot-strapped confidence interval 0.59-0.66). CONCLUSION: The validity of the ICF RA Core Set was supported by the perspective of individual patients. However, some additional issues raised in this study but not covered in the current ICF RA Core Set need to be investigated.     

Diagnosing Pouchitis

PURPOSE: Pouchitis represents a serious threat to patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The frequency of pouchitis is high, and it implies the risk of pouch failure and the risk of malignant mucosal transformation in the pouch. Early detection and precise classification of the inflammatory process are required for adequate therapy, which might be facilitated using a scoring system. The aim of the present study was to validate two existing scoring systems in routine outpatient practice. METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis Disease Activity Index developed at the Mayo Clinic were simultaneously prospectively applied in a consecutive series of 103 outpatient consultations of 41 patients at our hospital and comparatively validated against the diagnosis of pouchitis or no pouchitis concurrently made by a physician and a surgeon. RESULTS: The median score of examinations in which the clinicians diagnosis was consistent with pouchitis were significantly higher than those of examinations inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis Activity Score, 17 (interquartile range, 14–21) and 8 (interquartile range, 5–10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile range, 5–8) and 2.5 (interquartile range, 1–4), respectively, P < 0.001). The sensitivity and specificity in the two total scores were 84 and 79.5 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent, respectively (Pouchitis Disease Activity Index); in the field clinical manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index); in the field endoscopic manifestations 88 and 83.3 percent, respectively (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively (Pouchitis Disease Activity Index); and in the field histologic manifestations 72 and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and 96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index by 2 points (pouchitis: score 5) would result in an 88 percent sensitivity and a 67 percent specificity. CONCLUSIONS: Specificity and sensitivity of the Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be lowered to reach an acceptable sensitivity and specificity. The very poor validity of the field clinical manifestations in diagnosing pouchitis emphasizes the need for endoscopic and histologic examination for detection of pouchitis. The issue of whether the diagnosis of pouchitis should be based on endoscopic and histologic features alone, instead of additionally taking clinical features into account, should be addressed in future studies.     

Fibrinogen adsorption--a new treatment option for venous leg ulcers?

The initial element in the causation of venous ulceration is a disturbance of venous blood flow that leads to an increase in venous pressure. Eventually, however, it is the microcirculatory consequences of venous hypertension that lead to trophic skin changes and finally to ulceration. A reduction in blood viscosity results in an improvement at the microcirculatory level. The elimination of fibrinogen from plasma improves blood viscosity. This case report concerns a 75-year-old woman with venous ulcers of both legs (left lower leg: deep ulceration with a surface area of 3 x 5 cm; right lower leg: superficial, confluent ulceration with a total surface area of 5 x 10 cm). The patient underwent 20 sessions of fibrinogen adsorption, while simultaneously continuing with a regimen of conservative measures (activated charcoal cloth dressing with silver, calcium alginate dressings and short-stretch compression bandages). Following binding to a peptide (Gly-Pro-Arg-Pro-Lys), fibrinogen and fibrin were specifically removed from the patient's plasma: her fibrinogen concentration was lowered from an original mean level of 310 mg/dl (SD +/- 104 mg/dl) to 136 mg/dl (SD +/- 54 mg/dl), and there was no return to the baseline concentration by the time of the next fibrinogen adsorption session. In response to this treatment the patient's ulcers healed rapidly within 9 weeks. Dizziness and hematomas at the vascular access sites in both antecubital fossae were reported as adverse effects. A fall in hematocrit was also noted (before treatment 37% +/- 1%; after treatment 35% +/- 2%). This may have been caused by hemodilution due to the procedure and to cell losses during blood-plasma separation, a phenomenon that is known to occur during apheresis. This case report suggests that fibrinogen adsorption is low in adverse effects and is a useful addition to the range of treatments available for ulcers of venous etiology.     

Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis

The protumorigenic insulin-like growth factor (IGF)-II is highly expressed in a significant fraction of human hepatocellular carcinomas (HCC). However, a functional dissection that clarifies the contribution of IGF-II-binding receptors in tumor progression and a respective molecular characterization of IGF-II signaling has not been performed. Therefore, expression of IGF-II and its receptors IGF-receptor type I (IGF-IR) and insulin receptor (IR) was efficiently blocked using small interfering RNA (siRNA) in HCC cells. Despite functional IR-signaling, oncogenic IGF-II effects such as tumor cell viability, proliferation, and anti-apoptosis were solely transmitted by IGF-IR. Although IGF-II signaling was previously not described in the context of HCC cell migration, the IGF-II-dependent expression profile displayed a high percentage of genes involved in cell motility and adhesion. Indeed, IGF-II overexpression promoted HCC cell migration, especially in synergy with hepatocyte growth factor (HGF). The therapeutic relevance of IGF-II/IGF-IR signaling was tested in vitro and in a murine xenograft transplantation model using the IGF-IR inhibitor picropodophyllin (PPP). IGF-IR inhibition by small molecule treatment efficiently reduced IGF-II-dependent signaling and all protumorigenic properties of the IGF-II/IGF-IR pathway. CONCLUSION: In human HCC cells, IGF-IR but not IR is involved in oncogenic IGF-II signaling. Autocrine stimulation of IGF-II induces HCC motility by integration of paracrine signals for full malignant competence. Thus, activation of IGF-II/IGF-IR signaling is likely a progression switch selected by function that promotes tumor cell dissemination and aggressive tumor behavior.     

Failed antireflux surgery: quality of life and surgical outcome after laparoscopic refundoplication

BACKGROUND AND AIMS: Laparoscopic antireflux surgery has in recent years become the standard procedure for treating severe gastroesophageal reflux disease. Both laparoscopic antireflux surgery and open surgery cause failures which lead to repeat surgery in 3-6% of cases. We evaluated prospectively quality of life and surgical outcome following laparoscopic refundoplication for failed initial antireflux surgery. PATIENTS AND METHODS: We prospectively studied 51 patients undergoing laparoscopic refundoplication for primary failed antireflux surgery, with complete follow-up 1 year after surgery. In 20 cases the initial surgery used the open technique; four had surgery twice previously. In 31 cases primary procedure was performed laparoscopically. Indication for repeat surgery were recurrent reflux ( n=29), dysphagia ( n=12), and a combination of the two ( n=10). Preoperative and postoperative data including 24-h pH monitoring, esophageal manometry, and quality of life (Gastrointestinal Quality of Life Index) were used to assess outcome. RESULTS: Forty-nine procedures (96%) were completed by the laparoscopic technique. Conversion was necessary in two cases with primary open procedure, in one patient because of injury to the gastric wall and in one severe bleeding of the spleen. Postoperatively two patients (3.9%) suffered from dysphagia and required pneumatic dilatation within the first postoperative year. Average operating time was 245 min after an initial open procedure and 80 min after an initial laparoscopic procedure. The lower esophageal sphincter pressure increased significantly from preoperatively 2.8+/-1.8 mmHg at 3 months (12.8+/-4.1 mmHg) and 1 year (12.3+/-3.9 mmHg) after repeat surgery. In these cases the DeMeester score decreased significantly from preoperative 67.9+/-10.3 to 15.5+/-9.4 at 3 months and 13.1+/-8.1 at 1 year after surgery. Mean Gastrointestinal Quality of Life Index increased from 86.7 points preoperatively to 121.6 points at 3 months and 123.8 points at 1 year and was comparable to that of a healthy population (122.6 points). CONCLUSION: Laparoscopic repeat surgery for recurrent or persistent symptoms of gastroesophageal reflux disease is effective and can be performed safely with excellent postoperative results and a significant improvement in patient's quality of life for a follow-up period of 1 year.     

The Rodent Tibia Fracture Model: A Critical Review and Comparison With the Complex Regional Pain Syndrome Literature

Distal limb fracture is the most common cause of complex regional pain syndrome (CRPS), thus the rodent tibia fracture model (TFM) was developed to study CRPS pathogenesis. This comprehensive review summarizes the published TFM research and compares these experimental results with the CRPS literature. The TFM generated spontaneous and evoked pain behaviors, inflammatory symptoms (edema, warmth), and trophic changes (skin thickening, osteoporosis) resembling symptoms in early CRPS. Neuropeptides, inflammatory cytokines, and nerve growth factor (NGF) have been linked to pain behaviors, inflammation, and trophic changes in the TFM model and proliferating keratinocytes were identified as the primary source of cutaneous cytokines and NGF. Tibia fracture also activated spinal glia and upregulated spinal neuropeptide, cytokine, and NGF expression, and in the brain it changed dendritic architecture. B cell-expressed immunoglobulin M antibodies also contributed to pain behavior, indicating a role for adaptive immunity. These results modeled many findings in early CRPS, but significant differences were also noted.

Weight status,diet quality,perceived stress,and functional health of caregivers of children with autism spectrum disorder

1 Purpose

Caring for children with autism spectrum disorder (ASD) can be highly demanding and can put significant strain on caregivers. To date, little is known about the extent to which caregivers of children with ASD experience increased levels of stress which may adversely affect health outcomes. The purpose of this secondary analysis was to compare caregivers of children with ASD and caregivers of typically developing children (TDC) in weight status, diet quality, perceived stress related to the parenting role, and functional health and well‐being.

2 Design and methods

Caregivers of 25 children with ASD and 30 TDC completed the 2005 Block Food Frequency Questionnaire, the 36‐item Short Form of the Parenting Stress Index (PSI/SF), and the Short Form Health Survey (SF‐36) and had their heights and weights measured during an onsite visit. Diet quality was assessed using the Healthy Eating Index (HEI)‐2010 and its dietary components and conformance to the 2010 Dietary Guidelines for Americans.

3 Results

ASD caregivers did not differ significantly from TDC caregivers in body mass index or overweight/obesity prevalence (p ≥ .28), even when controlling for covariates. In univariate analyses, ASD caregivers consumed significantly fewer empty calories from solid fats, alcohol, and added sugars than TDC caregivers (p = .03), but they did not differ significantly in any other dietary outcomes including nutrient adequacy (p ≥ .10) and mean total HEI scores (p = .20). ASD caregivers, when compared to TDC caregivers, reported significantly greater parenting stress for the subscales difficult child and parent–child dysfunctional interaction as well as total stress (p < .001). In addition, 56% of ASD caregivers compared with 6.7% of TDC caregivers showed clinically significant levels of stress (p < .0001); a finding which remained statistically significant when controlling for covariates. ASD and TDC caregivers did not differ significantly in any SF‐36 health domains related to functional health and well‐being (p ≥ .10).

4 Practice implications

Despite higher reported levels of stress, ASD caregivers did not differ significantly from TDC caregivers in diet‐ and health‐related outcomes. Nurses and other health professionals should use comprehensive screening tools to assess overall caregiver stress and levels of resilience.     

Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy

Purpose

Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported.

Case Report

A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed.

Results

Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again.

Conclusion

Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC.Key Words: Punctate inner choroidopathy, Choroidal neovascularization, Intravitreal anti-VEGF therapy, Choroiditis