Reporting patient compliance

Once diagnosed hereditary hemochromatosis can be treated by weekly venesection of approximately 0.5 L of blood. The amount of iron removed in this way is usually around 250 mg per 0.5 L of blood. The intensive therapy lasts for 2-3 years depending on the iron present. A recent study reported patient compliance with this form of treatment. Another treatment option is chelation therapy by deferoxamine but this is an expensive treatment and the iron removal is slower its main use is with non-HFE hemochromatosis. 

An examination of the published literature does not suggest that this problem is extensive, although there are some reports [20] of high intrasubject variability. There is no reason to doubt that statisticians are well able to develop tests that could be used to quantify intrasubject variability [9,20-24]. However, the question as to how serious or widespread this problem may be in clinical practice is still in need of reliable data. In clinical use it is possible that for many, if not all drugs, intrapatient variability may well be more a function of patient compliances, variations in diet, use of other... 

The major adverse effect of niacin treatment is intense cutaneous flushing (vasodilation), which manifests as an uncomfortable burning sensation and itchiness of the face and upper body, thereby limiting patient compliance to therapy [13]. Moreover, a short half-life, dyspepsia, hyperuricemia, and modest hyperglycemia were also reported [14-16]. 

Physicians reported mixed feelings about the impact of DTCA on their patients and practices— More than 70 percent felt that DTCA helped educate patients about available treatments 67% felt that DTCA helped them have better discussions with their patients, ffowever, four out of five doctors believed that DTCA did not provide information in a balanced manner, and a similar number felt that it encouraged patients to seek treatments they did not need. Physicians as a group were more equivocal about other impacts of DTCA, with 46 percent agreeing that it increased patients compliance and 32 percent that it made patients less confident in their doctors judgment. Overall, 40 percent felt that DTCA had a positive effect on their patients and their practices, 30% felt it had a negative effect, and 30% felt that it had no effect. ... 

Oral controlled drug-release systems are increasingly used for short half-life drugs to reduce peak blood levels and side-eflfects, to maintain optimum drug concentration and to stimulate patient compliance. In order to maintain a constant blood-level of the drug during an extended period, a constant in vitro drug release rate is desired. The most popular controlled-release system is the matrix tablet (Desai et al., 1965). Te Wierik et al. (1996) reported on... 

Propranolol is chemically a naphthol derivative (dl-(isopropylamino)-3-(l-naphthyloxy)-2-propanol). It is a racemic mixture, and the laevo form is the active P-adrenergic blocking agent [10]. After oral administration, it is completely absorbed [11]. However, the systemic availability is relatively low with considerable variation in plasma levels [12,13]. The hepatic extraction of propranolol is about 80- 90%, and thus the main route of drug elimination is via hepatic metabolism [14]. One of the maj or metabolites of propranolol is 4-hydroxypropranolol, and the half-life has been reported to be 3 l-l/2h [15-18]. Since the drug is rapidly metabolized after oral administration, it necessitates a multiple dosage after oral strict patient compliance. 

The reported incidence of resistance to these drugs varies greatly, from less than 5% to 75%. In part this tremendous variation in incidence reflects the definition of resistance (recurrent thrombosis while on antiplatelet therapy vs in vitro testing), methods by which drug response is measured, and patient compliance. Several methods for testing aspirin and clopidogrel resistance in vitro are now FDA-approved however, their utility outside of clinical trials remains controversial. 

Advances in measurement have freed the estimation of patient compliance from its long-standing dependence on methods easily manipulated by patients, whose reluctance to acknowledge poor compliance contributes to self-reporting bias, documented in many ways. The years 1986-1987 saw the introduction of chemical marker and electronic monitoring methods, which provide different but complementary estimates of the time history of dosing by ambulatory patients. These advances have been extensively reviewed (Feinstein, 1990 Pullar and Feely, 1990 Urquhart, 1990 Cramer and Spilker, 1991 Bond and Hussar, 1991 Vander Stichele, 1991 Kruse, 1992). The gist of both methods is as follows. 

Dietary fibre and diabetes. The addition of gel-forming (soluble) but unabsorbable fibre (guar gum, a hydrocoUoidal polysaccharide of galactose and mannose from seeds of the cluster bean ) to the diet of diabetics reduces carbohydrate absorption and flattens the postprandial blood glucose curve. Reduced need for insixlin and oral agents are reported, but adequate amoimts (taken with lots of water) are impleasant (flatulence) and patient compliance is therefore poor. 

As might be expected, the presence of food in the gastrointestinal tract has been shown to affect lithium absorption and a diurnal variation in renal lithium clearance has been reported 183, 184). In our experiments, diurnal and other factors appeared to influence lithium pharmacokinetics to a greater degree than did formulation differences 182). We conclude that the practice of administering an early evening dose after a meal may delay the lithium peak sufficiently to reduce the possible discomfort of any transient side effects and may improve patient compliance. This is more important than the choice of preparation to be given. 

Hydrophilic matrix formulation of high-dose drugs (approximating 1.0g) is challenging because of the overall dosage weight limitations versus the quantity of the polymer required to achieve desired release profiles. It has been reported that very large tablets that are formulated to be swallowed whole (e.g. ER and delayed-release formulations) lead to poor patient compliance and therefore reduced market acceptability [50]. 

---