Definition Of Treatment Success Research Articles

Natalizumab for induction of remission in Crohn's disease

The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri(R), Elan Pharmaceuticals and Biogen Idec) a recombinant humanized IgG4 monoclonal antibody that blocks adhesion and subsequent migration of leukocytes into the gut by binding the alpha4 integrin is a member of a new class of molecules known as selective adhesion molecule (SAM) inhibitors. The results of animal studies suggest that alpha4 integrin blockade could be a useful therapy for inflammatory bowel disease. The results of randomized controlled trials suggest that natalizumab may be an effective therapy for active Crohn's disease. This systematic review summarizes the current evidence on the use of natalizumab for the induction of remission in Crohn's disease. To determine the efficacy and safety of natalizumab for induction of remission in Crohn's disease. A computer assisted search of the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Trials Register, MEDLINE and EMBASE was performed to identify relevant publications between 1966 and September 2006. The medical subject heading (MeSH) terms "Crohn disease" or "inflammatory bowel disease", "Natalizumab" or "Antegren" or "Tysabri" and "Antibodies, Monoclonal" were used to perform key word searches of each database. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Personal contacts, leaders in the field, and the manufacturers were contacted to identify other studies which may not be published. We included only randomized controlled trials comparing natalizumab to a placebo or control therapy for the induction of remission in Crohn's disease. Data were analyzed using Review Manager (RevMan 4.2.8). All data were analyzed on an intention-to-treat basis. For pooled data, summary test statistics were derived using the relative risk and 95% confidence intervals. Fixed and random effects models were used where appropriate. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar. Pooled data from the four included studies suggest that natalizumab (300 mg or 3 to 4 mg/kg) is effective for induction of clinical response and remission in patients with moderately to severely active Crohn's disease. This benefit is statistically significant for one, two and three infusion treatments. There was a trend toward increased benefit with additional infusions of natalizumab. Natalizumab appears to provide greater benefit for patient subgroups characterized by objective confirmation of active inflammation or chronically active disease despite conventional therapies. These subgroup analyses demonstrated significantly greater clinical response and remission rates for natalizumab compared with placebo in patients with elevated C-reactive protein levels, active disease despite the use of immunosuppressants, or prior anti-tumor necrosis factor therapy. These benefits were apparent for both short term (one infusion) and longer term treatment (two or three infusions). Natalizumab was generally well tolerated and the safety profile observed in the four included studies was similar. Adverse events occurred infrequently and were experienced by a similar proportion of natalizumab and placebo treated patients. There were no statistically significant differences between natalizumab and placebo treated patients in the proportions of patients who withdrew due to adverse events or those who experienced serious adverse events. The included trials lacked adequate power to detect serious adverse events that occur infrequently. Recently, two patients with multiple sclerosis treated with natalizumab in combination with interferon beta-1a and one patient with Crohn's disease treated with natalizumab in combination with azathioprine developed progressive multifocal leukoencephalopathy (PML) resulting in two patient deaths. A retrospective investigation was conducted to assess the risk of PML in natalizumab treated patients and no new cases were identified. Pooled data suggest that natalizumab is effective for induction of clinical response and remission in some patients with moderately to severely active Crohn's disease. The clinical benefit of induction therapy with natalizumab in Crohn's disease should be weighed against the potential risk of serious adverse events. Preliminary data from the retrospective investigation of adverse events associated with natalizumab suggest that it may be possible to identify patients at risk for PML by testing for the appearance of JC virus in plasma.

Clinical Experience of Extracorporeal Shock Wave Lithotripsy (ESWL) using a Dornier Compact S®

Purpose: We analyzed the efficacy and safety of extracorporeal shock wave lithotripsy (ESWL) for treating patient with urinary tract calculi with using a Dornier Compact S lithotriptor. Materials and Methods: We retrospectively reviewed the records of all the patient who had urinary calculi and who were treated by ESWL between August 1, 1996 and August 1, 2001. The location and sizes of the stones, the number of sessions, the success rate, the causes of failure and the complications of ESWL were analyzed. The definition of successful treatment was no calcification on the X-ray (plain film, KUB) or residual fragments ≤3mm in size. Results: Of the 470 cases, there were 157 (33.4%) and 313 (66.6%) cases of renal stones and ureteral stones, respectively. The total success rate was 94.3% (445/470), with success rates of 97.4%, 90.8%, 82.1% and 88.9% for stone sized 31mm, respectively. Conclusions: The results showed that ESWL is a highly effective and minimally invasive treatment modality as the 1st therapeutic option for urinary stones. The Dornier Compact S is an efficient and safe lithotripter that's capable of treating stones in the kidney and throughout the ureter. (Korean J Urol 2006;47:938-944) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

An Economic Evaluation of Triptan Products for Migraine

A composite outcome measure in migraine treatment assessment is useful to clinical decision-makers and payers as it can provide a more accurate reflection of effectiveness and allows for more complete modeling of economic value. The objective of this study was to compare the total triptan cost to treat 100 migraine patient attacks and the cost per successfully treated patient (CPSTP) for six marketed triptans using a composite measure of effectiveness, the "successfully treated" migraine (defined as requiring only one triptan dose to treat one migraine attack during a 24-h period). This analysis was conducted from the perspective of the payer. Clinical data were abstracted from a rigorous, published meta-analysis. Two-hour response and pain-free response were used in conjunction with the recurrence rate reported in the meta-analysis to calculate the number of doses used by treatment successes and failures. The average wholesale price per dose was then used to calculate total triptan cost. Of the nine oral triptan doses compared, eletriptan 40 mg was associated with both the lowest total triptan cost for treating 100 migraine attacks ($1560) and with the lowest CPSTP ($56.39). The relative CPSTP rankings for migraine therapies are dependent on the definition of treatment success and relative pricing. The results of this study support the use of eletriptan for the treatment of acute migraine based on the model assumptions. This study can be used to assist in formulary considerations and offers a model that can be adapted by health-care decision-makers.

57: Women′s Preferences for AUB Treatment and their Definition of a Successful Outcome Compared to Ob/Gyn Recommendations

To compare the preferences for treatment of AUB and definition of treatment success between women and their Ob/Gyns. Opinion research conducted March 14–18, 2005. Margin of error for a sample of 400 respondents is ±4.9% of that actually reported. Opinion research conducted March 14–18, 2005. Margin of error for a sample of 400 respondents is ±4.9% of that actually reported. Four hundred women ages 35–49 years. Average age was 41.9 years. Women were treated 22 months ago, on average, had waited an average of 16 months before speaking to their doctor. Of women treated for AUB who told their Ob/Gyn what result they wanted, 80% said it was to reduce their level of bleeding and 18% said it was amenorrhea (one-third had already agreed to a hysterectomy). Similarly 77% of Ob/Gyns told these patients success was less bleeding and (21%) of Ob/Gyns told these patients amenorrhea defined success. Forty-four percent preferred some type of medical procedure; they report that over half (54%) of their Ob/Gyns recommend one. Significantly more women treated 2+ years ago vs. treated 1–2 years ago chose hysterectomy (34% vs. 17%). Significantly more Ob/Gyns recommended D&Cs 2 + years ago vs. 2 years ago or less (37% vs. 11%). For the small sample of women (n=40) who said their Ob/Gyn recommended GEA, 70% were told by their Ob/Gyns that treatment success was a reduced level of bleeding vs. 23% who said amenorrhea; 48% of these women reacted positively to the idea of amenorrhea, 23% negatively and 31% were neutral or not sure. 98% agree that women should be given choices on AUB treatment. Our data suggest that patient preferences must be fully explored to determine what AUB treatment best fits needs/expectations. We note that the majority of women want less bleeding and the minority wants amenorrhea.

Cyclosporine for induction of remission in Crohn's disease

Cyclosporine was first found to be an effective and well-tolerated immunosuppressive agent in organ transplant recipients, and subsequently in several autoimmune diseases. It was reported in open studies that cyclosporine is effective for induction of remission in Crohn's disease. Four randomized controlled trials have been performed to determine whether the results observed in these open studies were valid. This systematic review summarizes the evidence on the use of oral cyclosporine for the induction of remission in Crohn's disease. To evaluate the effectiveness of oral cyclosporine for induction of remission in patients with active Crohn's disease in the presence and absence of concomitant steroid therapy. Secondary objectives were to evaluate clinical response rates and adverse events associated with cyclosporine. Computer-assisted searches of the on-line bibliographic databases MEDLINE and EMBASE were performed to identify potentially relevant publications between 1980 and July 2004. The MeSH terms "Crohn Disease" or "Inflammatory Bowel disease" and "Cyclosporin" (exploded) were used to perform key word searches of the databases. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed. Abstracts from major gastroenterological meetings, The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched for relevant studies. Appropriate officials at Sandoz Corporation were contacted to seek information on any unpublished trials. Prospective, randomized, double-blinded, placebo-controlled trials of parallel design with treatment duration of a minimum 12 weeks comparing oral cyclosporine therapy with placebo for treatment of patients with active Crohn's disease were eligible for inclusion. All data were analyzed on an intention-to-treat basis. Data were extracted from the original research articles and converted into 2x2 tables (cyclosporine vs. placebo). Where available, individual 2x2 tables for strata within studies were also used. Heterogeneity was assessed using the chi-square test (p < 0.10 was regarded as statistically significant). For non-pooled data, p-values were derived using the chi-square test. For pooled data, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. A fixed effects model was used for pooling of data. For continuous data, summary test statistics were derived using the weighted mean difference and 95% confidence intervals. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar. Brynskov 1989a found that patients receiving high dose cyclosporine (median 7.6 mg/kg/day) had statistically significant clinical improvement at 12 weeks compared to placebo patients. None of the other studies found any statistically significant benefit for clinical improvement or induction of remission for low dose cyclosporine treatment (5 mg/kg/day) used by itself or in combination with corticosteroids compared to placebo. Cyclosporine was associated with a significantly higher proportion of adverse events and withdrawals due to adverse events relative to placebo. Brynskov 1989a enrolled a small number of patients and the modified clinical grading scale used in the study has not been validated in other studies. Furthermore, statistically significant clinical improvement does not imply induction of clinical remission. Indeed, Brynskov 1989a found no statistically significant differences in the mean Crohn's Disease Activity Index score at 12 weeks indicating that cyclosporine was no more effective than placebo for induction of remission in Crohn's disease. The results of this review demonstrate that low dose (5 mg/kg/day) oral cyclosporine is not effective for the induction of remission in Crohn's disease. Patients treated with low dose oral cyclosporine are more likely than placebo treated patients to experience adverse events including renal dysfunction. The use of low dose oral cyclosporine for the treatment of chronic active Crohn's disease does not appear to be justified. Oral dosing at higher levels or parenteral administration of cyclosporine have not been adequately evaluated in controlled clinical trials. Higher doses of cyclosporine are not likely to be useful for the long-term management of Crohn's disease because of the risk of nephrotoxicity and the availability of other proven interventions.

Systemic therapy does not usually clear psoriasis, but treatment success does not require clearing

T he current regulatory definition of treatment success as clearing or near clearing may be excessively stringent for patients with severe psoriasis. We show that a majority of patients with severe psoriasis are not achieving clearing or near clearing, yet may be satisfied with systemic treatment. We assessed patients with psoriasis currently using methotrexate, psoralen plus ultraviolet A (PUVA), acitretin, or cyclosporine. Extent of disease was based on self-report (none or little,\3 palms, 310 palms, or[10 palms). Global treatment satisfaction was measured on a 10-point scale. Of 90 patients receiving systemic treatment, only 13 (14.4%) reported little to no psoriasis. Of the 90, 61 (67.8%) reported having 3 or more palms of psoriasis (Table I). A significantly larger proportion of patients reported global treatment satisfaction (41%) than dissatisfaction (14.4%, P = .001, chisquare test; Table II). Less than one third of patients with more than 10 palms of psoriasis were dissatisfied. Patients with psoriasis want their physicians to take their disease seriously, to treat it in a way they perceive to be adequately aggressive, and to prescribe a higher-risk systemic therapy when appro-

The association between pain and disability

A clearer understanding of how pain intensity relates to disability could have important implications for pain treatment goals and definitions of treatment success. The objectives of this study were to determine the optimal pain intensity rating (0–10 scale) cutpoints for discriminating disability levels among individuals with work-related carpal tunnel syndrome (CTS) and low back (LB) injuries, whether these cutpoints differed for these conditions and for different disability measures, and whether the relationship between pain intensity and disability was linear in each injury group. Approximately 3 weeks after filing work injury claims, 2183 workers (1059 CTS; 1124 LB) who still had pain completed pain and disability measures. In the LB group, pain intensity rating categories of 1–4, 5–6, and 7–10 optimally discriminated disability levels for all four disability measures examined. In the CTS group, no pain intensity rating categorization scheme proved superior across all disability measures. For all disability measures examined, the relationship between pain intensity and disability level was linear in the CTS group, but nonlinear in the LB group. Among study participants with work-related back injuries, when pain level was 1–4, a decrease in pain of more than 1-point corresponded to clinically meaningful improvement in functioning, but when pain was rated as 5–10, a 2-point decrease was necessary for clinically meaningful improvement in functioning. The findings indicate that classifying numerical pain ratings into categories corresponding to levels of disability may be useful in establishing treatment goals, but that classification schemes must be validated separately for different pain conditions.

Dynamics of serum cortisol levels after transsphenoidal surgery in a cohort of patients with Cushing's disease.

Transsphenoidal pituitary surgery is the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure, there is no agreement regarding the definition of successful treatment. We prospectively studied postoperative serum cortisol dynamics in 41 patients with CD (including a total of 45 surgeries). The mean postoperative follow-up period was 4.8 yr. Remission was defined as clinical and laboratory signs of adrenal insufficiency, glucocorticoid dependence, and serum cortisol suppression on overnight oral 1-mg dexamethasone suppression test. Serum cortisol was measured preoperatively and postoperatively at 6, 12, and 24 h (28 surgeries) and at 10-12 d (45 surgeries). No statistical difference was detected in mean preoperative and 6-h postoperative cortisol levels between surgically induced remission patients [22.1 +/- 7.73 microg/dl (610 +/- 213.3 nmol/liter) and 25.2 +/- 19 microg/dl (695.2 +/- 524.4 nmol/liter)] and surgical failure patients [23.6 +/- 6.95 micro g/dl (651.4 +/- 161.8 nmol/liter) and 37.5 +/- 18.1 microg/dl (1035 +/- 499.6 nmol/liter); P = 0.50 and P = 0.17]. At 12 and 24 h after surgery, the difference was significant (P = 0.009 and P < 0.0001). Mean cortisol levels were 12.44 +/- 13.3 microg/dl (343.3 +/- 367.1 nmol/liter) and 4.72 +/- 6.72 microg/dl (130.3 +/- 185.5 nmol/liter) in the remission group and 26.3 +/- 7.06 microg/dl (725.9 +/- 194.8 nmol/liter) and 23.5 +/- 6.86 microg/dl (648.6 +/- 189.3 nmol/liter) in the failure group (P = 0.009; P < 0.0001). At 10-12 d after the procedure, the difference was also significant (P < 0.0001): cortisol levels were 2.52 +/- 3.32 microg/dl (69.5 +/- 91.6 nmol/liter) in the remission group and 24.9 +/- 13.3 microg/dl (687.2 +/- 367.1 nmol/liter) in the failure group. In conclusion, in the immediate postoperative period of transsphenoidal surgery, remission of CD is not necessarily defined by undetectable serum cortisol. During the first 10-12 d after surgery, cortisol nadir correctly classified the remission [cortisol, 7.0 microg/dl (193.2 nmol/liter) or less] and the failure groups [cortisol, 8.0 microg/dl (220.8 nmol/liter) or more]. Glucocorticoid should be administered only after laboratory and/or clinical evidence of adrenal insufficiency.

Interpretation of clinical trials for the treatment of diabetic neuropathy.

Since with currently available technical equipment normoglycemic metabolic control cannot be attained in diabetic patients to prevent diabetic neuropathy, in addition to optimizing metabolic control, drugs will be necessary for prophylaxis and treatment of diabetic neuropathy to reduce compromising symptoms, to prevent debilitating late sequelae and to reduce the prognostic impact. Long-term treatment requires optimal risk-benefit-cost ratios of drugs used. For the practicing physician, it may be difficult to judge from the literature whether proposed treatments are in fact beneficial when used in general practice. The following points should be kept in mind when drawing conclusions from the literature: 1) homogeneity of the neuropathy under discussion, 2) severity of the neuropathy, 3) metabolic control, 4) sufficient numbers of probands, 5) sufficient duration of treatment, 6) definition of treatment goals and the impact of surrogate variables, 7) reproducibility of outcome measures, 8) definition of successful treatment, 9) time-dependent changes in both treatment and placebo groups, 10) adequate statistical evaluation, 11) numerical presentation of treatment results, 12) generalization of trial results, 13) tolerable side effects, and 14) publication bias.

The Advantage of CO2-Treated Dental Necks, in Comparison with a Standard Method: Results of an in Vivo Study

Various methods are used for treatment of hypersensitive dental necks. They all aim to seal exposed dentinal tubules, which are open toward the oral cavity and transmit stimuli to the sensitive nerve endings of the tooth pulp. The main sealing materials are fluoride preparations, strontium chloride, and hydroxyapatite. However, these materials must be applied periodically to achieve permanent freedom from pain. Since the introduction of laser technology into dentistry, efforts have been made to treat dentine hypersensitivity with the laser. An in vitro study revealed that CO2 laser irradiation results in almost complete closure of the dentinal tubules in the dental neck region. In the present in vivo study, the efficacy of laser treatment was examined in 72 patients with dentine hypersensitivity and 72 control patients over a period of 12 weeks. When success was defined as complete freedom from pain, the success rate in the laser group was 94.5%; when marked pain relief was included in the definition of treatment success, 98.6% of the patients were treated successfully. Treatment of the control group with conventional dental neck fluoridation resulted in no marked improvement. Laser Doppler measurements of pulpal blood flow immediately before and after treatment revealed no effects of laser irradiation on pulpal blood flow. Dentine samples were obtained from the dental necks 6 weeks after laser treatment and examined with atomic absorption spectroscopy (AAS). Tin was present in the samples, which suggests that the combined laser treatment and fluoridation result in permanent integration of fluoride in the dentine surface.