Integrating an evidence-based assessment of benefit and risk in disease-modifying treatment of multiple sclerosis

ABSTRACT

Background: As results from an increasing number of clinical trials with disease-modifying drugs (DMDs) in multiple sclerosis (MS) become available, the challenge for the treating neurologist is how to decide on the appropriate therapy for an individual patient.

Objective: An International Working Group for Treatment Optimization in MS met to consider how the principles of evidence-based medicine (EBM) should be used to assess the current best evidence regarding the treatment of MS. This report summarizes the outcome from the workshop at which this topic was addressed.

Results: Class I evidence from head-to-head studies provides the best tool for direct comparisons of DMDs. However, other EBM approaches to data analysis from placebo-controlled trials can be used to help determine the benefits and risks of a particular DMD relative to placebo by calculating the number needed to treat to achieve a positive outcome, such as avoiding a relapse, and the number needed to harm to produce an additional adverse event, such as having a therapy-related dropout. This provides a structured basis for comparisons between DMDs.

Conclusion: While such comparisons have their limitations, particularly when drugs with substantially different side-effect profiles are to be compared, they can provide useful information to guide treatment decisions.     

A novel deletion mutation in LIPH gene causes autosomal recessive hypotrichosis (LAH2)

Autosomal recessive hypotrichosis is a rare hereditary disorder characterized by sparse hair on scalp and rest of the body of affected subjects. Recently, three clinically similar autosomal recessive forms of hypotrichosis [localized autosomal recessive hypotrichosis (LAH)1], LAH2 and LAH3 have been mapped on chromosomes 18q12.1, 3q27.3, and 13q14.11-q21.32, respectively. For these three loci, two genes DSG4 for LAH1 and LIPH for LAH2 have been identified. To date, only five mutations in DSG4 and two in LIPH genes have been reported. In this study, we have ascertained two large unrelated consanguineous Pakistani families with autosomal recessive form of hypotrichosis. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene on chromosome 3q27. Sequence analysis of the gene in the affected subjects from both the families revealed a novel deletion mutation in exon 5 (c.659-660delTA) causing frameshift and downstream premature termination codon. All the three mutations identified in the LIPH gene, including the one in this study, are deletion mutations.     

Informing food choices and health outcomes by use of the dietary glycemic index

Considerable epidemiologic evidence links consuming lower glycemic index (GI) diets with good health, particularly upon aging. The GI is a kinetic parameter that reflects the ability of carbohydrate (CHO) contained in consumed foods to raise blood glucose in vivo. Newer nutritional, clinical, and experimental data link intake of lower dietary GI foods to favorable outcomes of chronic diseases, and compel further examination of the record. Based upon the new information there are two specific questions: 1) should the GI concept be promoted as a way to prolong health, and 2) should food labels contain GI information? Further, what are the remaining concerns about methodological issues and consistency of epidemiological data and clinical trials that need to be resolved in order to exploit the benefits of consuming lower GI diets? These issues are addressed in this review.     

Transesophageal echocardiography and monitoring applications

Transesophageal echocardiography (TEE) is a widely used cardiac imaging technique that provides the clinician with a view of the heart as seen from the esophagus or stomach. Rapid advances in TEE transducer technology, coupled with the low-risk, semi-invasive nature of the procedure, have fueled its use for cardiac monitoring of surgical and critical care patients, in addition to diagnostic imaging. Many recent research studies have demonstrated the utility of TEE for direct, real-time evaluation of global and regional left ventricular function not achievable with current competing technologies at the bedside. As a result of these advantages, TEE has become an emerging tool in cardiac monitoring at many centers around the world.     

Necessary but not sufficient

Objective: To consider the impact on primary care patient outcomes of using both a screener to determine elevated anxiety levels among patients with previously undetected anxiety and a physician intervention to inform physicians of their patients’ conditions. Design: Participating physicians were randomized to either the demonstration or the control arm, and patients were assigned to a study arm based on the randomization of their physicians. The patients were followed for change in outcome measures during the five-month study period. Setting: A mixed-model health maintenance organization serving approximately 110,000 enrollees in central Colorado. Patients/participants: 573 patients who had unrecognized and untreated anxiety identified from the approximately 8,000 patients who completed the waiting room screening questionnaire. Interventions: A physician intervention served the dual function of 1) providing an educational demonstration of anxiety in the primary care setting and 2) providing a reporting system for summarizing the anxiety symptom levels and functioning status of the patients enrolled in the study. Measurements and main results: Patient outcomes were measured as changes in global anxiety scores, functioning and well-being, and patients’ reports of global improvements. Conclusions: The findings indicate that this method of reporting symptoms and functioning status to primary care physicians did not significantly change patient outcomes. Improvement in outcomes appeared to be more closely associated with the patient’s severity of psychological distress. Preliminary data from this study were presented at the Seventh Annual National Institute of Mental Health International Research Conference on Mental Health Problems in the General Health Care Sector, September 20–22, 1993, McLean, Virginia, and at the first Annual Symposium of Contributed Papers on Quality of Life at the Drug Information Association Workshop, April 26–27, 1993, Charleston, South Carolina. Supported by a grant from the Upjohn Company, Kalamazoo, Michigan, and Take Care, Colorado. (Note: Dr. Buesching is a former employee of the Upjohn Company but owns no stock or option to purchase further stock in the company. Ms. Mathias, Dr. Fifer, Dr. Mazonson, Dr. Lubeck, and Dr. Patrick own no stock or option in the Upjohn Company.)     

Assessing the needs of women and clinicians for the management of menopause in an HMO

Objective: To determine the perceived needs of perimenopausal women regarding the management of menopause and the resource needs of the clinicians who treat them. Setting: A large staff and group network model health maintenance organization (HMO) in New England. Participants: A random sample of 790 perimenopausal women aged 45–60 years who were members of the HMO in 1991, and a random sample of 180 clinicians in internal medicine, family practice, and obstetrics/gynecology practicing in the HMO during 1991. Method: Mailed surveys of women and clinicians were designed to assess possible needs and attitudes that could lead to the improvement of care for menopausal women. The chi-square test was used to determine differences in perceived needs and satisfaction levels among women with differences in self-reported menopausal status. The Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U test were used in the clinician survey to test for differences among specialties and between genders. Results: The key findings include that: 1) most (81%) of the women wanted to see a woman clinician, 2) many (50%) were interested in a menopause support group, 3) 30% reported that their care for menopause had been fair to poor, 4) only 55% of the primary care specialists (including internal medicine and family practice) reported high confidence in their abilities to treat menopause, compared with 68% of the obstetric/gynecology clinicians, and 5) 56% of the clinicians surveyed said that support from the HMO to their practices for the treatment of menopause was fair to poor. Conclusions: There is an opportunity for better care for perimenopausal women as reported by two sources, HMO clinicians and members. To provide this care, clinicians may need explicit guidelines as well as administrative supports such as educational materials and specialty access. Since the capability for menopausal care from clinicians in obstetrics/gynecology is perceived to be higher than that from primary care clinicians, an opportunity for cross-specialty collaboration and training may exist.