Observational research — opportunities and limitations

Medical research continues to progress in its ability to identify treatments and characteristics associated with benefits and adverse outcomes. The principal engine for the evaluation of treatment efficacy is the randomized controlled trial (RCT). Due to the cost and other considerations, RCTs cannot address all clinically important decisions. Observational research often is used to address issues not addressed or not addressable by RCTs. This article provides an overview of the benefits and limitations of observational research to serve as a guide to the interpretation of this category of research designs in diabetes investigations. The potential for bias is higher in observational research but there are design and analysis features that can address these concerns although not completely eliminate them. Pharmacoepidemiologic research may provide important information regarding relative safety and effectiveness of diabetes pharmaceuticals. Such research must effectively address the important issue of confounding by indication in order to produce clinically meaningful results. Other methods such as instrumental variable analysis are being employed to enable stronger causal inference but these methods also require fulfillment of several key assumptions that may or may not be realistic. Nearly all clinical decisions involve probabilistic reasoning and confronting uncertainly, so a realistic goal for observational research may not be the high standard set by RCTs but instead the level of certainty needed to influence a diagnostic or treatment decision.     

Recent advances in hepatitis C virus research and understanding the biology of the virus

Since the identification of hepatitis C virus (HCV) genome in 1989[1], a lot of progresses have been done about the understanding of HCV biology, natural history and therapeutic options. HCV is a member of the Flaviviridae viral family. Its genome is a positive simple strand RNA     

Vaccine-related autoimmune hepatitis: the same disease as idiopathic autoimmune hepatitis? Two clinical reports and review

Autoimmune hepatitis (AIH) develops in genetically predisposed individuals after an inciting or environmental trigger. These factors are unknown but may include viral infections, environmental toxins, drugs and vaccinations. Few reports are written about vaccination as potential trigger of autoimmune hepatitis. In this article, we additionally describe two vaccine-related cases of AIH. In both cases, long-term immune-suppressive therapy is demanded. Moreover, we present the cases of vaccine-related AIH from literature and compare these with idiopathic AIH and our own cases.     

Internal Procidentia of the Rectum — Treatment and Results

Thirty-nine patients, 34 women and 5 men, with internal procidentia have been studied regarding symptomatology and results of treatment. Nineteen women have been operated upon. The most common indication for operation was anal incontinence. Twenty patients have been treated conservatively with bulk laxatives. In the operated group, 11 were symptom-free, 5 had recurrences, 2 had unchanged symptoms and one patient was worse because of rectovaginal fistula. The 5 recurrences were operated upon according to the techniques of Graham and Moschcowitz (4, 5). One of the conservatively treated patients developed a rectal prolapse in the followup period.     

Relationship between autoimmune hepatitis and HLA-DR4 and DRβ allelic sequences in the third hypervariable region in Chinese

AIM To analyze the association of HLA-DRB1 withautoimmune hepatitis(AIH)in patients from China.METHODS In 32 patients and 48 healthy controls,polymerase chain reaction amplification with sequence-specific primers(PCR-SSP)was performed to examine theassociation of certain alleles or polymorphic sequences ofHLA-DRB1 with AIH.RESULTS HLA-DRB1 typing by PCR-SSP showed that DR4had a significantly increased frequency among patientswith AIH versus healthy control(46.9% versus 20.8%;relative risk=3.35,P=0.014).In subtypes of DR4,therewas a trend of increase in the gene frequency of DRB1~*0405 in patients with AIH versus healthy controls(21.9%vs 6.3%,P=0.04,but P_c=0.08).In addition,asignificant increase was found in the alleles frequencyencoding QRRAA from the third hyperpolymorphic regionof DR4 in the patients with AIH(86.7% of DR4 positivepatients vs 40.0% in DR4 positive controls,P=0.016,P_c=0.028,RR=9.75).CONCLUSION AIH in Chinese is associated with HLA-DR4.There is a relationship between QRRAA sequencewithin the third hyperpolymorphic region of the DRB alleleand AIH in Chinese.     

Results of a national consensus workshop: therapeutic algorithm in patients with follicular lymphoma—role of radioimmunotherapy

Radioimmunotherapy (RIT) was approved for the treatment of relapsed or refractory CD20-positive follicular lymphoma (FL), subsequent to rituximab containing primary therapy. However, an increasing number of clinical studies have suggested that RIT may be more efficacious in an earlier phase of the disease. Therefore, a consensus meeting was held in May 2005 to define the optimal setting of RIT in the therapeutic algorithm of patients with advanced stage of FL. RIT is an established therapeutic option in relapsed FL. According to the reviewed data, RIT should be preferably used as consolidation after initial tumor debulking. First-line RIT may be applied in patients not appropriate for chemotherapy induction. Current study concepts evaluate the role of RIT consolidation in combination with antibody maintenance to achieve a potentially curative approach even in patients with advanced stage disease. J. Wehmeyer is in hematological–oncological private practice.     

Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity.METHODS: We investigated the prevalence of autoantibodies in 123 chronic HCV-infected children before,during and after monotherapy with interferon-alpha (TFN-α) or combined treatment with interferon-α or peginterferon-α and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (LKM), the incidence of antithyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined.RESULTS: We found that 8% of children had autoantibodies before treatment. During treatment,18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-α treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism.CONCLUSION: Our data indicate a strong correlation between interferon-α treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.     

Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

AIM: To evaluate the prevalence of autoantibodies in chronic hepatitis C virus (HCV)-infected children focusing on thyroid autoimmunity. METHODS: We investigated the prevalence of auto-antibodies in 123 chronic HCV-infected children before, during and after monotherapy with interferon-alpha (IFN-alpha) or combined treatment with interferon-alpha or peginterferon-alpha and ribavirin. Besides antibodies against smooth muscle (SMA), nuclei (ANA), and liver/kidney microsomes (LKM), the incidence of anti-thyroid peroxidase antibodies as well as thyroid function parameters (TSH, FT3 and FT4) were determined. RESULTS: We found that 8% of children had autoantibodies before treatment. During treatment, 18% of children were found positive for at least one autoantibody; 15.5% of children developed pathologic thyroid values during IFN-alpha treatment compared to only one child before therapy. Six children had to be substituted while developing laboratory signs of hypothyroidism. CONCLUSION: Our data indicate a strong correlation between interferon-alpha treatment and autoimmune phenomena, notably the emergence of thyroid antibodies. The fact that some children required hormone replacement underlines the need of close monitoring in particularly those who respond to therapy and have to be treated for more than 6 mo.     

Prevalence of autoantibodies and the risk of autoimmune thyroid disease in children with chronic hepatitis C virus infection treated with interferon-α

INTRODUCTION Since the discovery of the hepatitis C virus (HCV) in 1989[1], an increasing number of studies report an association of chronic HCV infection with autoimmune phenomena. In studies among adult patients, the prevalence of autoantibodies in chro…     

Efficacy and safety of treatment with sofosbuvir/velpatasvir in patients aged 6–18 years with chronic hepatitis C—Results of the PANDAA-PED study

Background and Aims

The aim of this non-commercial, open-label, real-life, non-randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6–18 years with chronic hepatitis C virus (HCV) infection.

Methods

Fifty patients qualified for the 12-week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real-time polymerase chain reaction method) at 12 weeks posttreatment (SVR12).

Results

Median age of the participants was 10 (IQR 8–12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty-seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty-three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5–13) versus 9 (IQR 8–11) years (p = 0.008).

Conclusions

Results of the PANDAA-PED study indicated a 100% effectiveness of a 12-week therapy with SOF/VEL in children aged 6–18 years with chronic HCV infection and its good safety profile, in particular in younger patients.     

Does the Evidence Make a Difference in Consumer Behavior? Sales of Supplements Before and After Publication of Negative Research Results

Objective  To determine if the public consumption of herbs, vitamins, and supplements changes in light of emerging negative evidence. Methods  We describe trends in annual US sales of five major supplements in temporal relationship with publication of research from three top US general medical journals published from 2001 through early 2006 and the number of news citations associated with each publication using the Lexus-Nexis database. Results  In four of five supplements (St. John’s wort, echinacea, saw palmetto, and glucosamine), there was little or no change in sales trends after publication of research results. In one instance, however, dramatic changes in sales occurred following publication of data suggesting harm from high doses of vitamin E. Conclusion  Results reporting harm may have a greater impact on supplement consumption than those demonstrating lack of efficacy. In order for clinical trial evidence to influence public behavior, there needs to be a better understanding of the factors that influence the translation of evidence in the public. The views presented are those of the authors and do not necessarily represent the positions or policies of the National Institutes of Health, the Department of Health and Human Services, or the US Public Health Service.     

Current status of basic and clinical research studies in the field of gastroenterology in China

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