Subject improvement

Although a variety of interpretations have been issued, reversibility to bronchodilators is considered to be present when the FEV i increases by 200 ml and 12% of the pre-bronchodilator value. Although in the latest GINA guidelines this issue is no longer addressed, the same criteria have been used for evaluation of the response to corticosteroids. A corticosteroid trial compared spirometric tests before and at the end of oral prednisolone (e.g. 30 mg/d) taken for two weeks or a course of inhaled steroid (e.g. beclomethasone 500 pg twice daily or equivalent) taken for six weeks. A positive response to corticosteroids justified prescription of regular inhaled steroid. Subjective improvement as a single efficacy parameter is not considered to be a satisfactory end point. Objective improvement is seen in 10-20% of patients with COPD. 

Venderova, K., E. Ruzicka, V. Vorisek, and P. Visnovsky. Survey on cannabis use in Parkinson s disease subjective improvement of motor symptoms. Mov... 

Diabetic neuropathy Oral administration of methylcobalamin (500 meg three times daily for four months) resulted in subjective improvement in burning sensation, numbness, loss of sensation and muscle cramps. 

In Table 1.3 I have included the areas of physical and psychological health, which often do not feature in reviews. Methadone has significant adverse effects, as discussed below, and by no means do all patients report subjective improvements in health on the drug, as opposed to when taking street heroin or other opiates. However, if methadone treatment is adhered to, there is normalization of various circadian rhythms and endocrine effects... 

Arkona and his coworkers (259) investigated verapamil in comparison with lithium in a random-assignment, double-blind, crossover study of 15 manic patients (4 weeks of lithium or verapamil, To days of placebo, and then a crossover to the other agent). Subjects improved on lithium but unexpectedly worsened with verapamil. This was a well-controlled study of verapamil, but unfortunately did not confirm the previous results. Further, it is only available in abstract form, and the complete publication is needed to evaluate the study critically its outcome, however, suggested caution in interpretation of earlier positive results. 

Clinical studies in patients with sleep disorders have shown that oral melatonin supplementation may alter sleep architecture. Subjective improvements in sleep quality and improvements in sleep onset and sleep duration have been reported. However, the significance of these findings is impaired by many study limitations. 

In a double-blind study, 209 healthy adults were randomized to placebo or lovastatin 20 mg/day for 6 months (4). Placebo-treated subjects improved between baseline and post-treatment periods on neuropsychological tests in all performance domains (neuropsychological performance, depression, hostility, and quality of life), consistent with the effects of practice on test performance, whereas those treated with lovastatin improved only on tests of memory recall. Comparisons of the changes in performance between placebo and lovastatin showed small but significant differences for tests of attention... 

Dietary supplementation studies with n-3 fatty acids alone have generally not been promising in atopic dermatitis. An initial double-blind study reported a subjective improvement on fish oil compared with the control OA, but no objective improvement on physician assessment.179 A further double-blind study using EPA with saturated fatty acids as the control, showed equal improvement with both supplements and the benefit was attributed to increased clinician guidance,180 while a multicenter study showed a similar improvement in clinical score in subjects taking fish oil or corn oil.181 The latter results might possibly reflect a beneficial effect of both EFA-containing oils, but more likely imply a placebo effect, and illustrate the problems posed both in selection of a suitable control and the interpretation of such studies. 

A discrepancy between subjective improvement of spasticity versus objectively determined measurements was also noted by Ungerleider et al. who treated 13 MS patients (in a double blind, placebo controlled, cross-over study) who had serious side-effects on treatment with conventional drugs [138], With a dose of 7.5 mg zf9-THC, all patients reported a decrease in spasticity however, in objective functional tests (limb spasticity, co-ordination and weakness and reflexes) no improvement was noted. In contrast, Meinch et al. found that, on smoking marijuana in an open label trial, an MS patient showed improved mobility, reduced spasticity and tremor measured by objective methods [139],... 

Drainage therapy results in subjective improvement and decreases the risk of cholangitis. Techniques used include biliodigestive anastomosis, percutaneous trans-hepatic drainage or an endoprosthesis to bridge bile-duct stenosis. 

I have had some female patients with subjective improvement with their hirsutism brought about by polycystic ovary disease. This may be due in part to the fact that 5-alpha-reductase is elevated in women with that condition. I have also had far more success with Serenoa than with Vitex in the treatment of acne. Women with estrogen excess and acne during the luteal phase of the menstrual cycle do particularly well with this herb. While the... 

Venderova K, Ruzicka E, Vorisek V, Visnovsky P (2003) Cannabis and Parkinson s disease subjective improvement of symptoms and levodopa-induced dyskinesias. International Cannabinoid Research Society 13th Annual Symposium on the Cannabinoids, abstr 145... 

Sheiner and Beal (1983) presented the first study on the role of experimental design in one of their seminal papers on nonlinear mixed effects models. They showed that increasing the number of subjects improves parameter estimation accuracy, but that increasing the number of samples per subject subjects does not improve estimation to the same degree when the data were simulated from a 1-compartment model. Hence, it is better to have sparse data from more subjects than intensive pharmacokinetic data with fewer subjects. They also showed that relatively accurate and precise parameter estimates (except for residual variance) can be obtained using FO-approximation with as few as 50 subjects having a single sample collected per subject. Keep in mind, however, this was a very simple pharmacokinetic model with only two estimable parameters. 

When the number of samples per individual was increased to three, regardless of where the middle point was collected in time, the structural model parameters remained unbiased but the bias in the variance components was removed. When the number of subjects was increased to 100 and then 150, the bias and precision in the structural model parameters remained unchanged, but improved the estimation of the variance components. Hence, under these conditions, neither more data per subject nor more subjects improved the estimates of the fixed effects in the model. What were affected were the variance components. Both more data within a subject and more subjects resulted in better variance component estimation. 

An aspect of neuroleptic therapy that has been puzzling is the delay of three or more weeks before subjective improvement is noted, even though it can be shown that the drugs block D2 receptors at the beginning of therapy. It has been known for some time that schizophrenics have much higher levels of homovanillic acid (HVA), which is the major DA metabolite, than do healthy controls. The fact that HVA concentrations parallel alterations in DA turnover in the brain has also been understood. It was demonstrated that fluphenazine steadily decreased HVA levels after several weeks and can ultimately reach normal values. Moreover, in patients that were evaluated, improvement correlates well with the HVA levels. This delayed effectiveness, then, may indicate that decreased DA turnover is the important factor rather than the immediate DA receptor blockade. It should be realized that in humans antipsychotics may have increased HVA levels in the CSF over the first few weeks, apparently because of DA blockade, which likely increases DA synthesis as a compensatory mechanism in the presynaptic neuron. After that initial 3-week period, however, DA turnover decreases to normal levels while the drug is continuing. 

Recent research on the modification of 14-membered macrolides and their structure-activity relationships has focused mainly on two subjects Improvement of their antimicrobial activity and spectra, including those for macrolide-resistant and Gram-negative pathogens, and optimization of their pharmacokinetic... 

In a subset of -10% of patients with myasthenic syndrome, muscle weakness has a congenital rather than an autoimmune basis, with mutations in the ACh receptor that effect ligand-binding and channel-opening kinetics, or in a form of AChE tethered by a collagen-like tail. Administration of anti-ChE agents does not result in subjective improvement in most congenital myasthenic patients. 

Pharmacology Melatonin has been used extensively for jet lag and as an alternative to prescription drugs for insomnia. In jet lag, clinical studies have shown subjective improvements in mood, more rapid recovery times, and reductions in daytime fatigue. 

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