Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD.

Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1±29.35 ng/ml; P<0.001; change in TSAT, 8.62%±1.57%; P<0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P<0.001), and the percentage of subjects not requiring iv iron was higher with FC (P<0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.

Ferric citrate controls phosphorus and delivers iron in patients on dialysis.

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.

Small bowel adenocarcinoma: Case reports and review of the literature.

Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal tract. Patients often present with advanced disease due to nonspecific symptoms and delayed diagnoses. In combination with non-uniform treatment paradigms, patients who present with SBA often have poor prognoses. In this case series, we present four cases of SBA and review the most recent literature with regard to diagnosis and management. One patient presented with iron-deficient anemia (IDA), and three patients presented with clinical obstruction. The patient with IDA was subjected to protracted investigations, whereas the three patients with obstruction were diagnosed quickly after presentation. All four patients underwent surgical resection, and one patient was eligible for post-operative adjuvant chemotherapy. SBA should be highly suspected in patients who present with occult gastrointestinal bleeds, and appropriate investigations must be initiated. Following diagnosis, surgical resection is the mainstay of treatment for this disease. Our review supports the use of both neoadjuvant and adjuvant chemotherapy in localized disease.

Intensive cognitive therapy for PTSD: a feasibility study.

BACKGROUND: Cognitive Behaviour Therapy (CBT) of anxiety disorders is usually delivered in weekly or biweekly sessions. There is evidence that intensive CBT can be effective in phobias and obsessive compulsive disorder. Studies of intensive CBT for posttraumatic stress disorder (PTSD) are lacking. METHOD: A feasibility study tested the acceptability and efficacy of an intensive version of Cognitive Therapy for PTSD (CT-PTSD) in 14 patients drawn from consecutive referrals. Patients received up to 18 hours of therapy over a period of 5 to 7 working days, followed by 1 session a week later and up to 3 follow-up sessions. RESULTS: Intensive CT-PTSD was well tolerated and 85.7 % of patients no longer had PTSD at the end of treatment. Patients treated with intensive CT-PTSD achieved similar overall outcomes as a comparable group of patients treated with weekly CT-PTSD in an earlier study, but the intensive treatment improved PTSD symptoms over a shorter period of time and led to greater reductions in depression. CONCLUSIONS: The results suggest that intensive CT-PTSD is a feasible and promising alternative to weekly treatment that warrants further evaluation in randomized trials.

Implementation of cognitive therapy for PTSD in routine clinical care: effectiveness and moderators of outcome in a consecutive sample.

OBJECTIVE: Trauma-focused psychological treatments are recommended as first-line treatments for Posttraumatic Stress Disorder (PTSD), but clinicians may be concerned that the good outcomes observed in randomized controlled trials (RCTs) may not generalize to the wide range of traumas and presentations seen in clinical practice. This study investigated whether Cognitive Therapy for PTSD (CT-PTSD) can be effectively implemented into a UK National Health Service Outpatient Clinic serving a defined ethnically mixed urban catchment area. METHOD: A consecutive sample of 330 patients with PTSD (age 17-83) following a wide range of traumas were treated by 34 therapists, who received training and supervision in CT-PTSD. Pre and post treatment data (PTSD symptoms, anxiety, depression) were collected for all patients, including dropouts. Hierarchical linear modeling investigated candidate moderators of outcome and therapist effects. RESULTS: CT-PTSD was well tolerated and led to very large improvement in PTSD symptoms, depression and anxiety. The majority of patients showed reliable improvement/clinically significant change: intent-to-treat: 78.8%/57.3%; completer: 84.5%/65.1%. Dropouts and unreliable attenders had worse outcome. Statistically reliable symptom exacerbation with treatment was observed in only 1.2% of patients. Treatment gains were maintained during follow-up (M=280 days, n=220). Few of the selection criteria used in some RCTs, demographic, diagnostic and trauma characteristics moderated treatment outcome, and only social problems and needing treatment for multiple traumas showed unique moderation effects. There were no random effects of therapist on symptom improvement, but therapists who were inexperienced in CT-PTSD had more dropouts than those with greater experience. CONCLUSIONS: The results support the effectiveness of CT-PTSD and suggest that trauma-focused cognitive behavior therapy can be successfully implemented in routine clinical services treating patients with a wide range of traumas.

A demonstration of the efficacy of two of the components of cognitive therapy for social phobia.

Cognitive-behavioral treatments have demonstrated efficacy in the treatment of social phobia. However, such treatments comprise a complex set of procedures, and there has been little investigation of the effects of individual procedures. The current study investigates the effects of two single session procedures that form part of cognitive therapy for social phobia [Clark, D., Ehlers, A., McManus, F., Hackmann, A., Fennell, M., Campbell, H., et al. (2003). Cognitive therapy vs fluoxetine in the treatment of social phobia: A randomised placebo controlled trial. Journal of Consulting and Clinical Psychology, 71, 1058-1067; Clark, D., Ehlers, A., McManus, F., Fennell, M., Grey, N., Waddington, L., et al. (2006). Cognitive therapy versus exposure and applied relaxation in social phobia: A randomised controlled trial. Journal of Consulting and Clinical Psychology, 74, 568-578], namely the "self-focused attention and safety behaviors experiment" and the "video feedback experiment." Results suggest that both procedures are effective in achieving their aims, which are: (i) demonstrating to patients the role of self-focused attention, safety behaviors, and excessively negative self-impressions in maintaining social phobia and (ii) reducing the symptoms of social phobia.