Patient experience in systemic lupus erythematosus: development of novel patient-reported symptom and patient-reported impact measures.

BACKGROUND: Comprehensive assessment of systemic lupus erythematosus (SLE) and its treatment requires patient-reported outcome (PRO) measures to capture impacts and fluctuating symptoms. The objective of this study was to develop PROs, in accordance with the Food and Drug Administration (FDA) PRO Guidance, to assess fluctuations in SLE symptoms and its impact. METHODS: Following independent review board approval, six US rheumatology practices recruited patients with SLE to participate in concept elicitation (CE) interviews, in order to identify important SLE symptoms and their impacts. The SLE Symptom Severity Diary (SSD) and SLE Impact Questionnaire (SIQ) were drafted based on CE interview results and clinician input. The PROs were revised based on patient feedback from cognitive debriefing (CD) interviews, clinician feedback, and a translatability assessment. RESULTS: Forty-one patients completed CE interviews. Commonly-reported symptoms included fatigue (98%), joint pain (93%), and rash (88%). The most frequently reported impact was difficulty with chores/housework (61%). Eighteen patients completed CD interviews. The PROs were considered comprehensive, clear, and relevant.The SSD contains 17 items assessing energy/vitality, joint and muscle pain/stiffness/swelling, flu-like symptoms, cognition, numbness/tingling, skin symptoms and hair loss using an 11-point numeric response scale and a 24-h recall period (with the exception of hair loss). It also evaluates steroid status and dose. The SIQ contains 50 items, uses a 5-point Likert scale and a 7-day recall period, to assess disease impacts including patients' ability to make plans, work, and physical/social/emotional functioning. CONCLUSION: The SSD and SIQ are comprehensive SLE-specific PROs developed in accordance with the FDA PRO Guidance. Following assessment of their measurement properties, they may be useful in clinical studies and clinical practice to measure fluctuations in, and the impact of, symptoms in patients with SLE.

Hypoglycaemic activity of Bixa orellana extract in the dog.

In West Indian folklore, a variety of plants are used for medicinal purposes. One such plant, Bixa orellana (annatto), is commonly used in the treatment of diabetes mellitus. Preliminary studies have shown that a crude annatto seed extract exhibited either glucose lowering or hyperglycaemia-inducing activity depending on how it was further manipulated. This present investigation sought to determine the effects of the glucose-lowering extract on C-peptide and streptozotocin-induced diabetic dogs. This annatto extract was found to decrease blood glucose levels in fasting normoglycaemic and streptozotocin-induced diabetic dogs. In addition, in normal dogs, it suppressed the postprandial rise in blood glucose after an oral glucose load. Interestingly, the extract also caused an increase in insulin-to-glucose ratio in normal dogs. Increased insulin levels were not due to increased insulin synthesis as after 1-h residence time and half-hour postprandial, decreased C-peptide levels was observed. It was concluded that Bixa orellana (annatto) lowered blood glucose by stimulating peripheral utilization of glucose, and it is possible that this glucose-lowering extract might be of pharmacological importance.

Investigation of plants used in Jamaican folk medicine for anti-bacterial activity.

We have started a systematic scientific study of folklore medicinal plants currently used as alternative medicine in Jamaican society. In this initial study, extracts of plants widely used by the islanders are studied for antibacterial activity against five common pathogens; Streptococcus group A, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa and Escherichia coli. These studies revealed that 25% (approx.) of the plant extracts had antimicrobial activity against at least one of the microbes used. Subsequent to these observations, extracts from Mikania micrantha were examined in detail. This led to the isolation of two sesquiterpenoids, mikanolide and dihydromikanolide, with activity against S. aureus and C. albicans. The results suggest that traditional folk medicine could be used as a guide in our continuing search for new natural products with potential medicinal properties.

Extraction of an hyperglycaemic principle from the annatto (Bixa orellana), a medicinal plant in the West Indies.

The red powdery extract from the seeds of the annatto, Bixa orellana, is a well known food colouring. In an oil suspension it is used as a folk remedy (bush tea) in the West Indies, for diabetes mellitus. Detailed investigations on this extract, yielded a methyl ester, trans-bixin, molecular weight 394 and molecular formula C24H30O4. This purified substance was demonstrated, in anaesthetised mongrel dogs, to cause hyperglycaemia. Concomitant electron microscopy of tissue biopsies, revealed damage to mitochondria and endoplasmic reticulum mainly in liver and pancreas. When dogs were fed on a diet fortified with riboflavin, there was neither demonstrable tissue damage nor associated hyperglycaemia. These findings point to: (i) the potential dangers of informal medications such as 'bush teas'; (ii) the possible role of plant extracts/food additives in the development of diabetes mellitus especially in the undernourished state.

Toxicity of the hyperglycaemic-inducing extract of the Annatto (Bixa orellana) in the dog

The Annatto seed coat extract, which is commonly used in folklore in treating diabetes mellitus, has been investigated for its effects on blood sugar levels in the dog. An alkali-soluble hyperglycaemia-inducing fraction was detected, and detailed studies revealed toxic effects in the pancreas and liver accompanied by hyperglycaemia and apparent tendency to increased insulin levels. The toxicity was diminished by feeding riboflavin. The relevance of this finding points to a possible aetiological role in the development of amlnutrition-related diabetes mellitus and also to the potential toxicity inherent in the widespread use of folklore medicines