The evolution of GM insulin 1983 - present
Filed under: Type 1, Type 2, Childhood, Adult Onset, Drugs, Opinion, Allie Beatty, Retro Review, Personalities
How did we allow insulin to evolve into a genetically modified hormone?
It all boils down to propaganda. If you're confident your current insulin surpasses former natural insulin in: purity, availability, allergy response, similarity and safety - I encourage you to review the following facts that were conveniently neglected or not available, due to restraints of time travel.
Purity: In the 1970s, a Genentech scientist stated that natural insulin was incredibly pure. In the 1980s, rDNA humulin insulins were less pure than the natural insulins of the 70s. The advertising campaign for rDNA insulin suggested otherwise. Here's a quote, as printed in the book, Invisible Frontiers: "They impressed upon us very, very clearly that this (human insulin) was going to be no advantage at all."
Supply and demand: A USDA scientist told the world the diabetic population's insulin needs would outstrip the supply of natural pancreatic glands. This was sensational propaganda. Have you visited McDonald's or Wendy's lately? There doesn't seem to be a shortage of Big Mac's, does there?
Allergy response: About 5-10% of the diabetic population is allergic to natural analog insulins. Today, based on 25 years of human diabetic experimentation, the diabetic population is showing the same 5-10% allergic response to all the new products. Maybe that aforementioned 5-10% is the same latter 5-10%? From the looks of it - they're just allergic to insulin, rDNA, GM or natural.
Similarity to own insulin: rDNA human insulin is just like the body makes. Who wouldn't want to take human insulin? That's the propaganda. A recent research article found in a large portion of the diabetic population, their own human insulin may actually be the cause of their diabetes. Something tells me the study included the same 5-10% of diabetics mentioned in the allergy response paragraph.
Safety: Drug companies touted rDNA insulins as providing a good a warning to diabetic patients as natural analog insulins regarding low blood glucose levels. Are you kidding me? Driver and workplace accident statistics regarding diabetics indicate that the rDNA insulins do not cross the blood-brain barrier in the same manner as natural analog insulins. The part of the brain controlling endocrine response lags because it doesn't get the signal until it's too late (if it ever gets the message). The increase of diabetes-realted deaths since the introduction of rDNA insulin is remarkable! (Center for Disease Control). How safe is that?
Fact versus fiction is a scary line to smear for the sake of business. I suggest doctors, diabetes educators, and patients review the facts today and compare it to the propaganda in the 80s. There is no suppressing the truth!
[RESEARCH] Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review
Objective To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women.
Design Systematic review.
Data sources Medline and Embase, the Cochrane Library, reference lists, and experts.
Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator.
Results 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria.
Conclusion The spot protein:creatinine ratio is a reasonable "rule-out" test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.
The thing that people with diabetes.hate the most
Filed under: Type 1, Type 2, Childhood, Drugs, Opinion, Allie Beatty, Retro Review, Personalities
I don't mind high sugars as much as I loathe lows. Personally I'm not so ruffled by shots either (but my liver begs to differ). However, in a message posted on The Islet Foundation, Pfizer reported that insulin-dependent diabetics declared they most hate taking shots. Was this the warm-up for the Exubera campaign? Here's a fact I support! A close second to this hatred is the hypos. Any diabetic will confess -- hypos are unforgiving. So what if you could catch two birds with one capsule?
I must reiterate the scientific genius behind the Oramed gel caps. The encapsulated insulin bypasses destruction in the stomach cavity. It reaches an entry point in the intestines where it reports for duty to the liver. This allows the liver to resume command of the glucose metabolism, just like Mother Nature intended. Whey you inject insulin - you are overriding the livers ability to monitor blood sugar and putting yourself in the line of fire for the dangerous lows. We all know this state of derangement too well. You won't find my lows picture on a milk carton if I happen to lose it, either.
Frequent episodes of hypoglycemia (even mild ones) force the brain to become accustomed to the low glucose. Unfortunately this also causes suppressed signaling of adrenaline, the livers last resort before dangerous lows. More specifically, the glucose transporters located in the brain cells are damaged from frequent episodes of hypoglycemia. So what was once the hypo threshold for the brain to signal adrenalin release becomes lower. Clinically, the result is hypoglycemic unawareness. Down with the shots, down with the lows and big ups with the future of diabetes control! Now we're getting somewhere.
[RESEARCH] Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis
Objective To determine if there is a relation between aspirin "resistance" and clinical outcomes in patients with cardiovascular disease.
Design Systematic review and meta-analysis.
Data source Electronic literature search without language restrictions of four databases and hand search of bibliographies for other relevant articles.
Review methods Inclusion criteria included a test for platelet responsiveness and clinical outcomes. Aspirin resistance was assessed, using a variety of platelet function assays.
Results 20 studies totalling 2930 patients with cardiovascular disease were identified. Most studies used aspirin regimens, ranging from 75-325 mg daily, and six studies included adjunct antiplatelet therapy. Compliance was confirmed directly in 14 studies and by telephone or interviews in three. Information was insufficient to assess compliance in three studies. Overall, 810 patients (28%) were classified as aspirin resistant. A cardiovascular related event occurred in 41% of patients (odds ratio 3.85, 95% confidence interval 3.08 to 4.80), death in 5.7% (5.99, 2.28 to 15.72), and an acute coronary syndrome in 39.4% (4.06, 2.96 to 5.56). Aspirin resistant patients did not benefit from other antiplatelet treatment.
Conclusion Patients who are resistant to aspirin are at a greater risk of clinically important cardiovascular morbidity long term than patients who are sensitive to aspirin.
[RESEARCH] Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials
Objective To review the published literature on the effectiveness of interventions to promote physical activity in children and adolescents.
Design Systematic review.
Data sources Literature search using PubMed, SCOPUS, Psychlit, Ovid Medline, Sportdiscus, and Embase up to December 2006.
Review methods Two independent reviewers assessed studies against the following inclusion criteria: controlled trial, comparison of intervention to promote physical activity with no intervention control condition, participants younger than 18 years, and reported statistical analyses of a physical activity outcome measure. Levels of evidence, accounting for methodological quality, were assessed for three types of intervention, five settings, and three target populations.
Results The literature search identified 57 studies: 33 aimed at children and 24 at adolescents. Twenty four studies were of high methodological quality, including 13 studies in children. Interventions that were found to be effective achieved increases ranging from an additional 2.6 minutes of physical education related physical activity to 283 minutes per week of overall physical activity. Among children, limited evidence for an effect was found for interventions targeting children from low socioeconomic populations, and environmental interventions. Strong evidence was found that school based interventions with involvement of the family or community and multicomponent interventions can increase physical activity in adolescents.
Conclusion Some evidence was found for potentially effective strategies to increase children's levels of physical activity. For adolescents, multicomponent interventions and interventions that included both school and family or community involvement have the potential to make important differences to levels of physical activity and should be promoted. A lack of high quality evaluations hampers conclusions concerning effectiveness, especially among children.
[RESEARCH] Interventions to promote walking: systematic review
Objective To assess the effects of interventions to promote walking in individuals and populations.
Design Systematic review.
Data sources Published and unpublished reports in any language identified by searching 25 electronic databases, by searching websites, reference lists, and existing systematic reviews, and by contacting experts.
Review methods Systematic search for and appraisal of controlled before and after studies of the effects of any type of intervention on how much people walk, the distribution of effects on walking between social groups, and any associated effects on overall physical activity, fitness, risk factors for disease, health, and wellbeing.
Results We included 19 randomised controlled trials and 29 non-randomised controlled studies. Interventions tailored to people's needs, targeted at the most sedentary or at those most motivated to change, and delivered either at the level of the individual (brief advice, supported use of pedometers, telecommunications) or household (individualised marketing) or through groups, can encourage people to walk more, although the sustainability, generalisability, and clinical benefits of many of these approaches are uncertain. Evidence for the effectiveness of interventions applied to workplaces, schools, communities, or areas typically depends on isolated studies or subgroup analysis.
Conclusions The most successful interventions could increase walking among targeted participants by up to 30-60 minutes a week on average, at least in the short term. From a perspective of improving population health, much of the research currently provides evidence of efficacy rather than effectiveness. Nevertheless, interventions to promote walking could contribute substantially towards increasing the activity levels of the most sedentary.
[RESEARCH] Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis
Objective To assess the risk of venous thromboembolism in women using hormone replacement therapy by study design, characteristics of the therapy and venous thromboembolism, and clinical background.
Design Systematic review and meta-analysis.
Data sources Medline.
Studies reviewed Eight observational studies and nine randomised controlled trials.
Inclusion criteria Studies on hormone replacement therapy that reported venous thromboembolism.
Review measures Homogeneity between studies was analysed using 2 and I2 statistics. Overall risk of venous thromboembolism was assessed from a fixed effects or random effects model.
Results Meta-analysis of observational studies showed that oral oestrogen but not transdermal oestrogen increased the risk of venous thromboembolism. Compared with non-users of oestrogen, the odds ratio of first time venous thromboembolism in current users of oral oestrogen was 2.5 (95% confidence interval 1.9 to 3.4) and in current users of transdermal oestrogen was 1.2 (0.9 to 1.7). Past users of oral oestrogen had a similar risk of venous thromboembolism to never users. The risk of venous thromboembolism in women using oral oestrogen was higher in the first year of treatment (4.0, 2.9 to 5.7) compared with treatment for more than one year (2.1, 1.3 to 3.8; P<0.05). No noticeable difference in the risk of venous thromboembolism was observed between unopposed oral oestrogen (2.2, 1.6 to 3.0) and opposed oral oestrogen (2.6, 2.0 to 3.2). Results from nine randomised controlled trials confirmed the increased risk of venous thromboembolism among women using oral oestrogen (2.1, 1.4 to 3.1). The combination of oral oestrogen and thrombogenic mutations or obesity further enhanced the risk of venous thromboembolism, whereas transdermal oestrogen did not seem to confer additional risk in women at high risk of venous thromboembolism.
Conclusion Oral oestrogen increases the risk of venous thromboembolism, especially during the first year of treatment. Transdermal oestrogen may be safer with respect to thrombotic risk. More data are required to investigate differences in risk across the wide variety of hormone regimens, especially the different types of progestogens.
[RESEARCH] Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis
Objective To evaluate the effect of oral decontamination on the incidence of ventilator associated pneumonia and mortality in mechanically ventilated adults.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, CINAHL, the Cochrane Library, trials registers, reference lists, conference proceedings, and investigators in the specialty.
Review methods Two independent reviewers screened studies for inclusion, assessed trial quality, and extracted data. Eligible trials were randomised controlled trials enrolling mechanically ventilated adults that compared the effects of daily oral application of antibiotics or antiseptics with no prophylaxis.
Results 11 trials totalling 3242 patients met the inclusion criteria. Among four trials with 1098 patients, oral application of antibiotics did not significantly reduce the incidence of ventilator associated pneumonia (relative risk 0.69, 95% confidence interval 0.41 to 1.18). In seven trials with 2144 patients, however, oral application of antiseptics significantly reduced the incidence of ventilator associated pneumonia (0.56, 0.39 to 0.81). When the results of the 11 trials were pooled, rates of ventilator associated pneumonia were lower among patients receiving either method of oral decontamination (0.61, 0.45 to 0.82). Mortality was not influenced by prophylaxis with either antibiotics (0.94, 0.73 to 1.21) or antiseptics (0.96, 0.69 to 1.33) nor was duration of mechanical ventilation or stay in the intensive care unit.
Conclusions Oral decontamination of mechanically ventilated adults using antiseptics is associated with a lower risk of ventilator associated pneumonia. Neither antiseptic nor antibiotic oral decontamination reduced mortality or duration of mechanical ventilation or stay in the intensive care unit.
[RESEARCH] Effectiveness of physiotherapy exercise after knee arthroplasty for osteoarthritis: systematic review and meta-analysis of randomised controlled trials
Objective To evaluate the effectiveness of physiotherapy exercise after elective primary total knee arthroplasty in patients with osteoarthritis.
Design Systematic review.
Data sources Database searches: AMED, CINAHL, Embase, King's Fund, Medline, Cochrane library (Cochrane reviews, Cochrane central register of controlled trials, DARE), PEDro, Department of Health national research register. Hand searches: Physiotherapy, Physical Therapy, Journal of Bone and Joint Surgery (Britain) Conference Proceedings.
Review methods Randomised controlled trials were reviewed if they included a physiotherapy exercise intervention compared with usual or standard physiotherapy care, or compared two types of exercise physiotherapy interventions meeting the review criteria, after discharge from hospital after elective primary total knee arthroplasty for osteoarthritis.
Outcome measures Functional activities of daily living, walking, quality of life, muscle strength, and range of motion in the knee joint. Trial quality was extensively evaluated. Narrative synthesis plus meta-analyses with fixed effect models, weighted mean differences, standardised effect sizes, and tests for heterogeneity.
Results Six trials were identified, five of which were suitable for inclusion in meta-analyses. There was a small to moderate standardised effect size (0.33, 95% confidence interval 0.07 to 0.58) in favour of functional exercise for function three to four months postoperatively. There were also small to moderate weighted mean differences of 2.9 (0.61 to 5.2) for range of joint motion and 1.66 (–1 to 4.3) for quality of life in favour of functional exercise three to four months postoperatively. Benefits of treatment were no longer evident at one year.
Conclusions Interventions including physiotherapy functional exercises after discharge result in short term benefit after elective primary total knee arthroplasty. Effect sizes are small to moderate, with no long term benefit.
[RESEARCH] Evidence for the impact of quality improvement collaboratives: systematic review
Objective To evaluate the effectiveness of quality improvement collaboratives in improving the quality of care.
Data sources Relevant studies through Medline, Embase, PsycINFO, CINAHL, and Cochrane databases.
Study selection Two reviewers independently extracted data on topics, participants, setting, study design, and outcomes.
Data synthesis Of 1104 articles identified, 72 were included in the study. Twelve reports representing nine studies (including two randomised controlled trials) used a controlled design to measure the effects of the quality improvement collaborative intervention on care processes or outcomes of care. Systematic review of these nine studies showed moderate positive results. Seven studies (including one randomised controlled trial) reported an effect on some of the selected outcome measures. Two studies (including one randomised controlled trial) did not show any significant effect.
Conclusions The evidence underlying quality improvement collaboratives is positive but limited and the effects cannot be predicted with great certainty. Considering that quality improvement collaboratives seem to play a key part in current strategies focused on accelerating improvement, but may have only modest effects on outcomes at best, further knowledge of the basic components effectiveness, cost effectiveness, and success factors is crucial to determine the value of quality improvement collaboratives.