Conventional Management Of Patients Research Articles

East Asian Traditional Medicine Treatment for Patients after Heart Valve Replacements: A Systematic Review with Meta-Analysis

Objectives: To compare the effectiveness and safety of East Asian traditional medicine treatments (EATMT) versus conventional management in patients following heart valve replacement surgery.Methods: We searched several databases, including the Korean Studies Information Service System, PubMed, China National Knowledge Infrastructure, and Citation Information by NII. The search range included randomized controlled trials from each first issue until June 27, 2021. Two review authors independently extracted the data. We assessed the risk of systematic errors by evaluating risk domains using the “Risk of bias” tool.Results: We included 5 trials in the review. In the EATMT, the investigators reported significant improvements in reshaping of the heart structure: left ventricular end diastolic diameter (MD -4.43, 95% CI -6.06 to -2.79; 130 participants; 2 studies; high evidence). Comparisons with usual care revealed a significant decrease in gastrointestinal complications rate (OR 0.30, 95% CI 0.20 to 0.47; 503 participants; 2 studies; high evidence). We assessed 4 studies as having a low risk of bias and 1 study as having a high risk of bias.Conclusion: This systematic review suggests that East Asian traditional medicine interventions may be effective in preventing and alleviating complications, but we found evidence of important trade-offs between known benefits and known adverse effects in cardiac dysfunction and inflammation following heart valve replacement. Consequently, additional high-quality studies should be conducted.

Proactive Therapeutic Drug Monitoring Versus Conventional Management for Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD. We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain predetermined trough concentration, regardless of disease activity) with conventional management (clinically driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations. On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96; 95% confidence interval [CI], 0.81-1.13) with moderate heterogeneity (inconsistency index= 36%) (Grading of Recommendations, Assessment, Development and Evaluations; low certainty evidence), with no differences in patients with Crohn's disease (RR, 0.87 ; 95% CI, 0.66-1.15) and ulcerative colitis (RR, 0.88; 95% CI, 0.72-1.07). Disease duration, concomitant immunomodulators, disease activity at baseline, and optimization of therapy before randomization did not modify this association. No differences were observed in risk of developing antidrug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR, 1.56; 95% CI, 1.25-1.94). Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations.

Role of catestatin in development and decompensation of heart failure: a literature review

The current literature review covers the role of sympathetic nervous system activation (SNS) and the significance of a new biomarker catestatin (CST), which is a chromogranin A-derived peptide, for assessing prognosis of patients with heart failure (HF). This review details the works devoted to CST metabolism and its role in clinical conditions with excessive catecholamine production, including the ability to counterbalance the adverse effects of SNS on cardiovascular system. The paper also presents the central results of studies on HF patients and shows the correlation of the CST level with HF functional class and stage. In addition, particular attention is paid on the possibilities and potential benefits of assessing the CST in addition to conventional management of patients hospitalized due to acute decompensated heart failure.

Outcomes of Enhanced Recovery After Surgery Protocols Versus Conventional Management in Patients Undergoing Bariatric Surgery.

Background: Enhanced recovery after surgery (ERAS) pathways focus on decreasing surgical stress and promoting return to normal function for patients undergoing surgical procedures. The aim of our study was to evaluate the impact of an ERAS protocol on outcomes of patients undergoing primary sleeve gastrectomy and Roux-en-Y gastric bypass. Outcomes included hospital length of stay (LOS), and management of postoperative pain and postoperative nausea and vomiting (PONV) measured by pain medications and antiemetic use, respectively. Incidence of 90-day emergency department (ED) visits, readmissions, and complications were also analyzed. Methods: A retrospective review was performed from October 1, 2016 to October 31, 2018 of patients enrolled in the ERAS versus the conventional pathway. Patient baseline characteristics, pain and nausea scores, LOS, and postoperative outcome variables were collected. Results: Non-ERAS (n = 193) and ERAS (n = 173) groups had similar patient characteristics. Fewer ERAS patients required postoperative opioids and antiemetics (P < .01), with a significant difference in postoperative nausea control in favor of ERAS patients (P < .05). There was a decreasing trend in median LOS (2 versus 1, P = .28), 90-day postoperative readmissions (10.4% versus 8.1%, P = .47), and major adverse events (5.2% versus 1.7%, P = .07) after ERAS implementation. The ED visits and postoperative need for intravenous fluid for dehydration were significantly lower in the ERAS group (P = .01). Conclusion: Implementation of ERAS pathway for bariatric surgery was associated with less opioid usage, PONV, ED visits, and postoperative need for intravenous fluids, without increasing LOS, 90-day readmission or rates of adverse effects.

Pharmacist-Directed Self-Management of Blood Pressure Versus Conventional Management in Patients with Hypertension: A Randomized Control Trial.

Data has shown that pharmacist-directed health services play a key role in the treatment of hypertension. We aimed to perform this study to compare two methods of the pharmacist-directed home blood pressure monitoring (HBPM) and the usual care. A total of 126 patients with uncontrolled blood pressure (BP) were randomized 1:1 into the pharmacist-directed HBPM and the usual care groups. In the intervention group, the patients were trained to measure their BPs and adjust their medications based on the designed protocol under the supervision of a clinical pharmacist. The primary endpoint of the study was the comparison of the BPs at baseline and months 1, 3, and 6. One month after the allocation, the baseline systolic BP (SBP) (150.5 ± 13.1 vs. 149.7 ± 11.2mm Hg; P = 0.71) and diastolic BP (DBP) (97.2 ± 9.8 vs. 93.6 ± 14.5; P = 0.11) significantly dropped to the control range equally in 85.2% of the patients in two groups (SBP: 128.8 ± 6.4 vs. 125.6 ± 7.1mm Hg; P = 0.01 and DBP: 89.1 ± 6.2 vs. 81.5 ± 6.0mm Hg; P = 0.01). This pattern continued during the study period (month 6; SBP: 115.6 ± 10.1vs. 116.1 ± 9.6mm Hg; P = 0.78; DBP: 79.0 ± 5.0 vs. 77.2 ± 5.8mm Hg; P = 0.08). In this study, we did not observe any significant difference between the pharmacist-directed HBPM and usual care methods in decreasing BP.

Short- and long-term outcomes associated with enhanced recovery after surgery protocol vs conventional management in patients undergoing laparoscopic gastrectomy.

BACKGROUNDAt present, the enhanced recovery after surgery (ERAS) protocol is widely implemented in the field of gastric surgery. However, the effect of the ERAS protocol on the long-term prognosis of gastric cancer has not been reported.AIMTo compare the effects of ERAS and conventional protocols on short-term outcomes and long-term prognosis after laparoscopic gastrectomy.METHODSWe retrospectively analyzed the data of 1026 consecutive patients who underwent laparoscopic gastrectomy between 2012 and 2015. The patients were divided into either an ERAS group or a conventional group. The groups were matched in a 1:1 ratio using propensity scores based on covariates that affect cancer survival. The primary outcomes were the 5-year overall and cancer-specific survival rates. The secondary outcomes were the postoperative short-term outcomes and inflammatory indexes.RESULTSThe patient demographics and baseline characteristics were similar between the two groups after matching. Compared to the conventional group, the ERAS group had a significantly shorter postoperative hospital day (7.09 d vs 8.67 d, P < 0.001), shorter time to first flatus, liquid intake, and ambulation (2.50 d vs 3.40 d, P < 0.001; 1.02 d vs 3.64 d, P < 0.001; 1.47 d vs 2.99 d, P < 0.001, respectively), and lower medical costs ($7621.75 vs $7814.16, P = 0.009). There was a significantly higher rate of postoperative complications among patients in the conventional group than among those in the ERAS group (18.1 vs 12.3, P = 0.030). Regarding inflammatory indexes, the C-reactive protein and procalcitonin levels on postoperative day 3/4 were significantly different between the two groups (P < 0.001 and P = 0.025, respectively). The ERAS protocol was associated with significantly improved 5-year overall survival and cancer-specific survival rates compared with conventional protocol (P = 0.013 and 0.032, respectively). When stratified by tumour stage, only the survival of patients with stage III disease was significantly different between the two groups (P = 0.044).CONCLUSIONAdherence to the ERAS protocol improves both the short-term outcomes and the 5-year overall survival and cancer-specific survival of patients after laparoscopic gastrectomy.

ECMO for severe ARDS: systematic review and individual patient data meta-analysis.

PurposeTo assess the effect of venovenous extracorporeal membrane oxygenation (ECMO) compared to conventional management in patients with severe acute respiratory distress syndrome (ARDS).MethodsWe conducted a systematic review and individual patient data meta-analysis of randomised controlled trials (RCTs) performed after Jan 1, 2000 comparing ECMO to conventional management in patients with severe ARDS. The primary outcome was 90-day mortality. Primary analysis was by intent-to-treat.ResultsWe identified two RCTs (CESAR and EOLIA) and combined data from 429 patients. On day 90, 77 of the 214 (36%) ECMO-group and 103 of the 215 (48%) control group patients had died (relative risk (RR), 0.75, 95% confidence interval (CI) 0.6–0.94; P = 0.013; I2 = 0%). In the per-protocol and as-treated analyses the RRs were 0.75 (95% CI 0.6–0.94) and 0.86 (95% CI 0.68–1.09), respectively. Rescue ECMO was used for 36 (17%) of the 215 control patients (35 in EOLIA and 1 in CESAR). The RR of 90-day treatment failure, defined as death for the ECMO-group and death or crossover to ECMO for the control group was 0.65 (95% CI 0.52–0.8; I2 = 0%). Patients randomised to ECMO had more days alive out of the ICU and without respiratory, cardiovascular, renal and neurological failure. The only significant treatment-covariate interaction in subgroups was lower mortality with ECMO in patients with two or less organs failing at randomization.ConclusionsIn this meta-analysis of individual patient data in severe ARDS, 90-day mortality was significantly lowered by ECMO compared with conventional management.Electronic supplementary materialThe online version of this article (10.1007/s00134-020-06248-3) contains supplementary material, which is available to authorized users.

Mechanical Ventilation for Acute Respiratory Distress Syndrome during Extracorporeal Life Support. Research and Practice.

Ventilator-induced lung injury remains a key contributor to the morbidity and mortality of acute respiratory distress syndrome (ARDS). Efforts to minimize this injury are typically limited by the need to preserve adequate gas exchange. In the most severe forms of the syndrome, extracorporeal life support is increasingly being deployed for severe hypoxemia or hypercapnic acidosis refractory to conventional ventilator management strategies. Data from a recent randomized controlled trial, a post hoc analysis of that trial, a meta-analysis, and a large international multicenter observational study suggest that extracorporeal life support, when combined with lower Vt and airway pressures than the current standard of care, may improve outcomes compared with conventional management in patients with the most severe forms of ARDS. These findings raise important questions not only about the optimal ventilation strategies for patients receiving extracorporeal support but also regarding how various mechanisms of lung injury in ARDS may potentially be mitigated by ultra-lung-protective ventilation strategies when gas exchange is sufficiently managed with the extracorporeal circuit. Additional studies are needed to more precisely delineate the best strategies for optimizing invasive mechanical ventilation in this patient population.

Intra-operative uterine artery embolization with caesarean delivery in an adjoining operating theatre and catheter lab (OT/CL) complex vs. conventional management in patients with abnormally invasive placenta: a retrospective case control study

Patients of abnormally invasive placenta (AIP) undergoing caesarean delivery are at increased risk of haemorrhage. Conventional management includes piecemeal removal of placenta or placenta left in situ. However, they often require hysterectomy after delivery. Post-delivery prophylactic uterine artery embolisation (UAE) can help reduce morbidity and preserve fertility. We created an adjoining operating theatre and catheter lab (OT/CL complex). This is a retrospective case control study in which 37 patients of AIP were evaluated. Sixteen subjects (cases) had UAE immediately after caesarean delivery, and 21 subjects (controls) had usual care with traditional methods of controlling postpartum haemorrhage and hysterectomy where required. The hysterectomy rate (18.7% vs. 85.7%), mean duration of hospital stay (6.8 ± 2.6 vs. 13.9 ± 8.1) and number of units of blood transfusion required were significantly less in the case group as compared with controls. UAE is an effective conservative treatment along with caesarean delivery in patients with AIP.Impact statementWhat is already known? AIP is associated with high rates of PPH, maternal morbidity and mortality and need for hysterectomy after delivery. UAE has been advocated to preserve fertility and reduce PPH in these patients along with caesarean delivery.What does the study add? We created an adjoining operating theatre and catheter lab (OT/CL complex) in a tertiary care centre and managed these patients with prompt UAE after caesarean delivery with team approach. We have shown significant reduction in morbidity and hospital stay with this coordinated management.What are the implications for clinical practice and/or further research? UAE with caesarean delivery is a preferred mode of delivery for patients of AIP. These patients should be diagnosed and referred to tertiary care centres with such facilities electively so as to provide optimal care to these patients. Cooperation between interventionist and obstetrician and adjoining availability of OT and catheter lab can further help in reducing the time to embolisation after delivery. A hybrid operating theatre with digital subtraction angiography (DSA) facilities would be ideal for the management of such patients.

Optimal duration of prone positioning in patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-regression analysis

IntroductionSeveral systematic reviews and meta-analyses have demonstrated that prolonged (≥16 hours) prone positioning can reduce the mortality associated with acute respiratory distress syndrome (ARDS). However, the effectiveness and optimal duration...

Changing treatment paradigms for the management of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory condition of the gastrointestinal tract causing bowel damage, hospitalizations, surgeries, and disability. Although there has been much progress in the management of IBD with established and evolving therapies, most current approaches have failed to change the natural course. Therefore, the treatment approach and follow-up of patients with IBD have undergone a significant change. Usage of immunosuppressants and/or biologics early during the course of the disease, known as top-down or accelerated step-up approach, was shown to be superior to conventional management in patients who had been recently diagnosed with IBD. This approach can be applied to selected groups based on prognostic factors to control disease activity and prevent progressive disease. Therapeutic targets have been shifted from clinical remission mainly based on symptoms to objective parameters such as endoscopic healing due to the discrepancies observed between symptoms, objectively evaluated inf lammatory activity, and intestinal damage. The concept of treat-to-target in IBD has been supported by population-based cohort studies, post hoc analysis of clinical trials, and meta-analysis, but more evidence is needed to support this concept to be applied to the clinical practice. In addition, individualized approach with tight monitoring of non-invasive biomarker such as C-reactive protein and fecal calprotectin and drug concentration has shown to improve clinical and endoscopic outcomes. An appropriate de-escalation strategy is considered based on patient demographics, disease features, current disease status, and patients’ preferences.

Late-Breaking Clinical Trial and Clinical Science Special Reports Abstracts From the American Heart Association's Scientific Sessions 2016; Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2016.

Late-Breaking Clinical Trial and Clinical Science Special Reports Abstracts From the American Heart Association's Scientific Sessions 2016; Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2016.

Seasonal Human Influenza: Treatment Options.

Opinion statementSeasonal influenza can be a self-limiting illness in healthy individuals but is associated with short-term morbidity and economic burden. Influenza can cause significant morbidity and mortality in young children, the elderly, pregnant and post-partum women, patients with co-morbidities and the immunocompromised. Neuraminidase inhibitors (NAIs) are the treatment of choice for influenza due to widespread resistance to the adamantanes. NAIs are efficacious for the treatment of influenza in ambulatory patients with mild illness, when initiated within 48 h of symptom onset. Early treatment with NAIs has been shown to reduce otitis media in children, and lower respiratory tract complications, resulting in antibiotic therapy, in adults. Evidence on the efficacy of NAIs for the prevention of influenza-related complications in at-risk populations, based on reviews of data from randomised trials is inconclusive. However, observational studies suggest that in hospitalised patients early treatment with NAIs has been associated with reduced mortality. NAIs should be initiated as soon as possible in patients at high-risk of influenza-related complications, with suspected or proven influenza, hospitalised patients and patients with severe or progressive disease. NAIs can be considered in previously healthy patients when therapy can be initiated within 48 h of symptom onset. In previously healthy patients, the therapeutic efficacy of oseltamivir is time-dependent, with maximal benefit observed when therapy is initiated within 48 h of symptom onset. However, several observational studies suggest therapeutic benefit beyond 48 h, in hospitalised patients, severe disease, and patients at high risk of complications, including pregnant women. NAIs should be considered in patients at high risk of influenza-related complications who present late. Further studies are needed to define the optimal timing of NAIs. Oseltamivir-resistant virus has been widely reported but is predominantly an issue in H1N1 seasonal influenza. Zanamivir-resistant influenza virus is rare, and inhaled or intravenous (IV) zanamivir is the treatment of choice in proven or suspected oseltamivir-resistant virus. Intubated patients with severe influenza can be treated with oseltamivir (suspension) administered via nasogastric tube. The commercial dry powder formulation of zanamivir should not be administered, via nebulisation, as it has been associated with ventilator malfunction and mortality. In intubated patients, when there are concerns about gastric absorption, IV zanamivir should be obtained under Emergency Investigational New Drug access schemes. Currently available evidence does not support the use of high-dose or extended-duration oseltamivir in patients with severe influenza, but does require further investigation. Extracorporeal membrane oxygenation has not been shown to be superior to conventional management in patients with influenza-associated acute respiratory distress syndrome and should be considered as salvage therapy. Corticosteriods should not be used in the treatment of severe influenza as this has been associated with increased risk of mortality and bacterial superinfection.

EComment. Post-sternotomy mediastinitis management: negative pressure is the key

I read with great interest the paper by Yu et al. in which they compare outcomes of vacuum-assisted closure (VAC) therapy with conventional management in patients with post-sternotomy mediastinitis (PSM) [1]. There is no general consensus concerning the appropriate surgical approach to PSM and multiple wound healing strategies have been proposed [2]. The treatment of PSM has changed radically with the advances made in VAC systems since the concept of negative wound pressure therapy was first described in the mid 1990s. VAC therapy was introduced to clinical practice in 1995 in North America and two years later it was available in Europe. Since the introduction of VAC techniques in the management of sternal wound infection, there has been a paradigm shift toward the use of this less invasive strategy as a first-line therapy in the management of PSM [2]. Although I recognize the efforts of Yu et al. in reviewing the literature to find the best strategy for patients with PSM, I would like to mention one important point that they failed to include in their report. Closed drainage with Redon catheters is another alternative technique for PSM first used by Durandy et al. [3]. The high negative pressure (-700 mmHg) induced by the bottles fulfils exactly the role of VAC in a different fashion. Vos et al. [4] were the first to perform a prospective study comparing clinical outcomes of VAC with primary closure using Redon catheter in the setting of PSM. They included in their study 161 patients with PSM; there were 89 patients in the VAC group and 43 patients in the Redon group. Both groups were similar in risk factors and severity of mediastinitis. Hospital stay was significantly shorter in the Redon group (45 + /-38 days) compared with the VAC group (74 + /-61 days). The in-hospital mortality rate was similar in both groups, however re-infection rate was higher in the VAC group probably due to the increased risk of wound contamination during dressing changes. The authors of the present study concluded that this treatment modality using Redon drains provides sternal wound healing without repeat intervention while significantly reducing the hospital stay without compromising mortality. By applying negative pressure to a sternal wound either by VAC or Redon drain connected to bottles several advantages are combined: removing exudate from the infected area and increasing blood flow into the wound. None of these studies is a randomized trial; therefore a prospective clinical trial is required to address this issue at a higher level of evidence. Conflict of interest: none declared

640 The utilisation of a remotely monitored implantable loop recorder as first line investigation in the diagnosis of syncope: The EaSyAS II study

Implantable loop recorder (ILR) technology offers the ability for prolonged monitoring of the syncopal patient, allowing the best chance of achieving symptom-rhythm correlation. In our randomised study we compared the immediate use of a remotely monitored ILR in the initial investigation of unexplained syncope, with conventional management in patients with recurrent unexplained syncope. 246 patients (age > 16 years, with ≥ 2 syncopal episodes within 2 years) were recruited over a 16 month period (2007 to 2009) into the Eastbourne Syncope Assessment Study II (EaSyAS II) and were randomised to conventional care alone, conventional care and syncope clinic attendance, ILR alone or ILR plus syncope clinic attendance. Primary outcomes were time to ECG diagnosis and time to institution of ECG directed therapy. Median follow up was 20 months (IQ Range 15-27). 120 patients received the ILR. All implants were undertaken as daycases and there were no implant related complications. A total of 62 ILR patients (50%) achieved ECG diagnosis compared with 1 conventionally managed patient. Mean time to diagnosis was 95.2 das post induction. ILR use resulted in a quicker time to ECG diagnosis and ECG directed therapy (HR 35.54, 95% CI 4.84-261.01, P = 0.0004). All ILR diagnoses were achieved at 1st post induction syncope with no data loss. ILR patients were less likely to experience a 2nd syncope compared to standard care patients (HR 0.38, 95% CI 0.17 - 0.86, P = 0.02). Syncope clinic care was the most cost effective (cost per diagnoses and cost per QALY) followed by ILR use. No benefit appeared to be gained by combining ILR and syncope clinic. Our findings support the hypothesis that a remotely monitored ILR can be used as a safe and cost effective first line investigation in recurrent unexplained syncope. It is associated with an increased diagnostic yield and quicker time to ECG diagnosis when compared to conventional management enabling prompt and appropriate ECG directed therapy. In addition continuous remote monitoring prevents data loss increases diagnostic rate from a spontaneous syncopal event.Tabled 1

A randomised control trial of early enteral nutrition v. conventional management in patients undergoing major resection for upper gastrointestinal cancer: a comparison of fluid management

A randomised control trial of early enteral nutrition v. conventional management in patients undergoing major resection for upper gastrointestinal cancer: a comparison of fluid management - Volume 68 Issue OCE1

Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial

Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial

Step-Up and Top-Down Approaches to the Treatment of Crohn's Disease: Early May Already Be Too Late

D'Haens G, Baert F, van Assche G, et al. (Department of Gastroenterology, Imelda Gastrointestinal Clinical Research Centre, Imelda General Hospital, Bonheiden, Belgium). Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 2008;371:660–667.

Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial

Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab. We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710. Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0). Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.

PEG-Intron Therapy in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders (MPD): Final Result of a Phase II Study.

The conventional management of patients (pts) with high-risk Philadelphia chromosome-negative (Ph-negative) MPD revolves around the administration of cytoreductive agents such as hydroxyurea, anagrelide, and recombinant human interferon alpha (IFN-a). IFN-a has shown significant activity in the treatment of Ph-negative MPD, particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-Intron is a pegylated IFN-a that has a significant advantage over regular IFN-a in that it is administered once a week. We are reporting the final results of a phase II study evaluating the efficacy and tolerability of PEG-Intron in pts with Ph-negative MPD treated at M. D. Anderson Cancer Center, Houston, Texas. PEG-Intron was given subcutaneously weekly with intent to treat pts as long as they benefit from the therapy. Forty pts were enrolled, 26 males (65%), with a median age of 54 years (range 28 to 81). Pts diagnoses were: 14 ET (35%); 11 myelofibrosis (MF; 27%); 6 Ph-negative chronic myeloid leukemia (CML; 15%); 4 hypereosinophilic syndrome (HES; 10%); 4 PV (10%); and 1 myelodysplastic syndrome/myeloproliferative disease (MDS/MPD; 3%). Thirty-four pts are evaluable for response evaluation, as they have received minimum of 3 months of therapy, and have received more than 50% of the medication during the time on study: complete remission (CR) was achieved in 13 pts (38%) while partial response (PR) was noted in 4 pts (12%); 17 pts (50%) had no response. Six pts were not evaluable for response: 2 refused therapy before starting; 3 stopped therapy early due to toxicity, and 1 had progression of the disease before 3 month response evaluation. Of the 17 responders 12 (71%) achieved their best response by 3 months on the therapy. Overall response among all the patients enrolled varied by the type of diagnosis: of the 14 ET pts 7 achieved CR and 2 achieved PR (64% overall response rate); of the 11 MF pts one achieved CR; of the 6 Ph-negative CML 2 achieved CR; of the 4 pts with HES one achieved CR; of 4 PV pts 2 achieved CR and 2 PR; and 1 MDS/MPD pt was not evaluable for response. Initially, starting dose of PEG-Intron was 3 mcg/kg per week. However, of the first 14 pts on the study all but 1 had to reduce the dose at least once within the first 3 months, and therefore the starting dose of PEG-Intron was reduced to 2 mcg/kg per week. Most of the pts maintained the 2 mcg/kg per week throughout their time on the therapy. Recorded grade 3 toxicities were related to myelosuppression, disturbance of GI tract, and musculo-skeletal system (22 pts). Grade 4 toxicities were recorded in 4 pts: 1 developed anemia and the other 3 developed thrombocytopenia. Of the 38 pts that have received any therapy 5 (4 in CR and 1 in PR) are still receiving therapy for a median duration of 28+ months (range, 21+ to 41+). Of the 33 pts that stopped the therapy 17 stopped because of no response, 6 due to unrelated medical reasons, 5 due to toxicity, 2 due to other reasons, 1 was lost to follow-up, 1 lost response, and 1 progressed to acute myeloid leukemia. After a median follow-up of 24 months (range, 1 to 42) 26 pts are alive. In conclusion, PEG-Intron, with proper dose modifications, is effective in controlling disease in a significant proportion of Ph-negative MPD pts, particularly patients with ET and PV. However, toxicities encountered with PEG-Intron therapy are still significant.