Kim Krogsgaard

Effectiveness of active physical training as treatment for long-standing adductor-related groin pain in athletes: randomised trial

BACKGROUNDnGroin pain is common among athletes. A major cause of long-standing problems is adductor-related groin pain. The purpose of this randomised clinical trial was to compare an active training programme (AT) with a physiotherapy treatment without active training (PT) in the treatment of adductor-related groin pain in athletes.nnnMETHODSn68 athletes with long-standing (median 40 weeks) adductor-related groin pain--after examination according to a standardised protocol--were randomly assigned to AT or PT. The treatment period was 8-12 weeks. 4 months after the end of treatment a standardised examination was done. The examining physician was unaware of the treatment allocation. The ultimate outcome measure was full return to sports at the same level without groin pain. Analyses were by intention to treat.nnnFINDINGSn23 patients in the AT group and four in the PT group returned to sports without groin pain (odds ratio, multiple-logistic-regression analysis, 12.7 [95% CI 3.4-47.2]). The subjective global assessments of the effect of the treatments showed a significant (p=0.006) linear trend towards a better effect in the AT group. A per-protocol analysis did not show appreciably different results.nnnINTERPRETATIONnAT with a programme aimed at improving strength and coordination of the muscles acting on the pelvis, in particular the adductor muscles, is very effective in the treatment of athletes with long-standing adductor-related groin pain. The potential preventive value of a short programme based upon the principles of AT should be assessed in future, randomised, clinical trials.

The treatment effect of alpha interferon in chronic hepatitis B is independent of pre-treatment variables. Results based on individual patient data from 10 clinical controlled trials

Alpha interferon induces HBeAg seroconversion in about one third of treated patients and has become an established treatment of chronic hepatitis B. A number of smaller studies have suggested that response to treatment is more likely to occur in patients with higher levels of transaminases, with recent (adult) onset, a history of acute hepatitis, low levels of HBV DNA and in heterosexual males. The aim of this European co-operative study was to estimate the effect of alpha interferon more accurately and to evaluate the influence of host pre-treatment variables on the effect of interferon. Individual data were collected from 751 patients from 10 controlled clinical trials on alpha interferon (lymphoblastoid or recombinant) treatment for chronic hepatitis B. Alpha interferon was administered to 496 patients, while 255 were untreated controls. Individual patient data were analysed by survival analysis (log rank test and Cox regression analysis), stratified by trial, with the disappearance of HBeAg as the major endpoint. The results showed that the HBeAg disappearance rate with or without interferon treatment was higher in patients with high aminotransferase levels, with a history of acute hepatitis and in male heterosexual patients disregarding HIV status. If HIV-positive patients were excluded, the effect of sexual orientation was not significant. Therapy with alpha interferon increased the a priori HBeAg disappearance rate by a factor of 1.76; the relative treatment effect of alpha interferon was independent of the tested pretreatment host variables, but dependent on the total (intended) interferon dose (low dose < or = 200 MU/m2 increased HBeAg disappearance by a factor 1.37; medium/high dose > or = 200 MU/m2 increased HBeAg disappearance by a factor 2.05). In conclusion, this meta-analysis suggests that the effect of alpha interferon is less than previously assumed and independent of pretreatment host variables tested. It confirms the higher therapeutic benefit of a total dose exceeding 200 MU/m2 and of selection of patients based on disease activity and immune reactivity. Although all patient seem to have the same relative benefit, the absolute benefit of alpha interferon treatment seems to be greatest in patients with high transaminase levels and with a history of acute hepatitis.

Prevalence and Prognostic Significance of Infection with TT Virus in Patients Infected with Human Immunodeficiency Virus

No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.

The long-term effect of treatment with interferon-α2a in chronic hepatitis B

This study was performed to evaluate the long‐term effects of interferon‐α2a (IFN‐α2a) vs no treatment in patients with chronic hepatitis B and to determine whether viral clearance, following therapy or occurring spontaneously, was sustained. Patients originating from three previously published multicentre, randomized, controlled trials were analysed. Information about survival and response during long‐term follow‐up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA and loss of hepatitis B e antigen (HBeAg) and improvement in alanine aminotransferase level. Scheduled treatment‐free follow‐up was 12 months in all studies. Median long‐term follow‐up time after inclusion in the individual studies was 4.7 years (range: 0.2–7.5 years). Viral clearance after IFN‐α2a, or occurring spontaneously, was sustained in 70 out of 80 evaluable patients (88%) who were responders at the end of the original trials and 21 (30%) lost hepatitis B surface antigen (HBsAg). A total of 80 patients received (re)treatment during the long‐term follow‐up period and 33% of them responded, irrespective of previous treatment category. Overall response rate was not significantly affected by gender, sexual inclination or ethnic origin. Durability of response did not depend upon ethnic origin or presence of cirrhosis. At the end of the original trial periods, 253 patients were histologically evaluated and 22 (9%) had histologically confirmed progression to cirrhosis. During long‐term follow‐up an additional five patients developed cirrhosis. Hepatocellular carcinoma developed in three patients (1%): in one patient during the follow‐up period of the original trial and in two patients (one untreated) during the long‐term follow‐up period. Ten of 25 deaths were liver‐related (hepatocellular carcinoma in three, gastrointestinal bleeding in two and liver failure in five). The distribution of clinical events (progression to cirrhosis, hepatocellular carcinoma and liver‐related deaths) was unrelated to original treatment category and response to treatment. Hence, 90% of responding patients will, irrespective of treatment category, have a sustained response. At least 30% of responding patients will eventually lose HBsAg. For a number of reasons, the present patient population and observation period are insufficient to establish a presumed beneficial effect of IFN‐α2a on disease progression and survival.

A Randomized Trial Assessing the Impact of Written Information on Outpatients' Knowledge About and Attitude Toward Randomized Clinical Trials

To improve the patient education process in clinical research, three information materials describing general aspects of design and conduct of randomized clinical trials were developed. The materials varied in length, reading ability level, and reader appeal. Their influence on knowledge about and attitude toward randomized clinical trials was assessed in a randomized, parallel group, evaluator-blinded trial among 415 outpatients. The patients were randomized to the following groups: control (no intervention), leaflet, brochure, or booklet. Knowledge was assessed by a 17-item multiple-choice questionnaire and attitude was assessed by a 32-item Likert questionnaire at entry and 2 weeks after the intervention. The interventions and the questionnaires were pilot tested and power calculations were performed. At entry, the mean knowledge score was 7.9 points. At follow-up, the knowledge scores increased by 0.5 for the control, 1.0 for the leaflet, 1.6 for the brochure, and 1.4 for the booklet. The brochure and the booklet improved the knowledge score significantly compared with the control. The general attitude was positive at entry (mean 71.5 points). Only the booklet significantly increased the total attitude score (4.8 points) and the randomized clinical trials attitude subscale score (1.8 points). In conclusion, written information significantly improved outpatients knowledge about and attitude toward randomized clinical trials. Detailed rather than brief information was more effective. Control Clin Trials 2000;21:223-240

Cytomegalovirus Infection Rate among Heart Transplant Patients in Relation to Anti-thymocyte Immunoglobulin Induction Therapy

During a 2-year period, 49 patients underwent heart transplantation at Rigshospitalet, Copenhagen. Nine (18%) were females and the mean age for all patients was 44 years (range 14-56 years). Immunosuppressive therapy included cyclosporin, azathioprine and steroids in all patients. 43 patients received in addition short-term (approx. 4 days) induction treatment with antithymocyte immunoglobulin (ATG). 17 patients received ATG Fresenius, 2.5 mg/kg/day or ATGAM, 12.5 mg/kg/day, whereas the remaining 26 patients received ATG Merieux, 2.5 mg/kg/day. Prophylactic antimicrobial chemotherapy included ceftriaxone, acyclovir (1 g daily), nystatin, and pyrimethamine in toxoplasmosis mismatch patients. Serological assays for cytomegalovirus (CMV), Epstein-Barr virus, varicella-zoster virus, herpes simplex virus, legionella and toxoplasmosis as well as CMV and bacterial culturing were carried out before transplantation, at regular intervals and when clinically indicated. Five patients developed septicaemia. Nine had pulmonary bacterial infections, including 2 cases of legionella pneumonia. Two had Clostridium difficile diarrhoea. Three patients had Pneumocystis carinii pneumonitis. 24 patients (49%) had evidence of CMV infection/reactivation. Seven out of 10 CMV mismatch (pos donor/neg recipient) patients and 3 out of 12 CMV match (pos donor/pos recipient) patients developed clinical CMV disease. The rate of CMV infection/reactivation was significantly higher among patients who had CMV-positive donors (p < 0.01) and among patients receiving ATG Merieux induction treatment (p < 0.0001). Logistic regression analysis showed that both positive CMV donor status and ATG Merieux induction treatment were significant independent predictors of CMV infection. Six patients (12%) died. Two out of 4 infection related deaths could be ascribed to CMV disease.

VOIDING PROBLEMS IN PATIENTS WITH HIV INFECTION AND AIDS

The prevalence and type of urinary voiding problems were prospectively investigated in 77 men and four women (median age 36 years) with HIV infection or AIDS consecutively attending an outpatient clinic. Urologic symptoms were registered from replies to a questionnaire and urologic evaluation was made when indicated. All patients were neurologically examined. In addition, urodynamic data from ten consecutively referred HIV/AIDS patients were retrospectively analyzed. Two of the 81 prospectively studied patients had severe, and eight had moderate voiding problems, while 19 had pathologic findings at neurologic examination. Of three patients referred for urodynamic investigation, two were found to have neurogenic bladder dysfunction. In three of the total 13 urodynamically studied patients the findings suggested neurogenic bladder dysfunction secondary to the infection. We conclude that HIV/AIDS infection affects voiding only in minor degree, and when it does the disease is often advanced and dominated by symptoms from other organs. The relevance of urologic/urodynamic investigation in HIV/AIDS patients thus seems limited.

Relation between treatment efficacy and cumulative dose of alpha interferon in chronic hepatitis B

BACKGROUND/AIMSnAlpha interferon (IFN) is an established treatment of chronic hepatitis B. The effect has been shown to be dose related, recommended dose regimens being associated with a doubling of the spontaneous, baseline HBeAg to anti-HBe seroconversion rate. However, the efficacy of IFN treatment in relation to the dose of IFN actually received remains to be established. The aim of this study was to estimate the relative efficacy of IFN as a function of the cumulative IFN dose. In addition we determined if and when a patient returns to his baseline chance of seroconversion after stopping IFN therapy.nnnMATERIALS AND METHODSnIndividual patient data from 10 clinical controlled trials were available for the present analysis, in all, 746 patients, of whom 491 received IFN and 255 were untreated controls. The data were analyzed performing a time-dependent Cox regression analysis of the relative efficacy of IFN using the cumulative IFN dose administered up to any given time during the observation period and the time after termination of therapy as explanatory variables.nnnRESULTSnIn the proposed model, the chance of HBeAg disappearance for a treated patient relative to no therapy was estimated to 2.1 at a cumulative dose of 100 MU and leveled out at about 2.8 at a cumulative dose of 500 MU. The effect of IFN was shown to decay rapidly after discontinuation and after 3 months a patient could be considered to be back to his baseline chance of HBeAg disappearance. These findings show that IFN administered at a dose of 15-30 MU/week should be considered effective (relative efficacy approximately 2) already after 1-2 months of treatment.nnnCONCLUSIONSnThe present findings do not lend any support to the concept that IFN treatment becomes less effective when a certain total dose of IFN has been administered or that the treatment effect reaches beyond 3 months after stopping IFN.

Veno-occlusive disease and peliosis of the liver after thorotrast administration

A case of veno-occlusive disease and peliosis of the liver without coexisting liver malignancy 35 years after thorotrast administration is presented. In the liver four main widely distributed lesions were found: Venoocclusive disease (VOD), peliosis, fibrosis and thorotrast deposits. Whether the VOD and the peliotic lesions are pathogenetically related or totally independent cannot be determined in the present case. However, the VOD and the peliosis are possibly related to the protracted alpha-emitting effect of thorotrast deposited in the liver parenchyma.

Variables Predicting Elevated Portal Pressure in Alcoholic Liver Disease: Results of a Multivariate Analysis

In 46 alcoholic patients the association of wedged-to-free hepatic-vein pressure with other variables (clinical, histologic, hemodynamic, and liver function data) was studied by means of multiple regression analysis, taking the wedged-to-free hepatic-vein pressure as the dependent variable. Four variables showed significant independent association with the wedged-to-free hepatic-vein pressure: indocyanine green clearance (p = 0.031), degree of necrosis (p = 0.023), degree of hepatic architectural destruction (graded as: preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) (p = 2.3 X 10(-6) and sex (p = 0.0024), male sex being associated with higher wedged-to-free hepatic-vein pressure. The multiple coefficient of determination (R2) was 0.63; thus, 63% of the variation in the wedged-to-free hepatic-vein pressure was explained by variation in these four variables.