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Management and Analysis of Time-Related Data in Internet-Based Healthcare 45 may be matched against certain criteria (IF clause of the ECA rule) purchase terramycin 250 mg line antibiotics for acne and side effects. For example buy terramycin 250 mg online bacteria kits for science fair, the criteria may be that according to their profile it is not normal to be in bed during this period. When an instance of the events defined in the ON clause occurs, and given that the condition has been matched according to the IF clause this will lead to the system acting accordingly such as the DO clause. For example, a form of action/intervention must be taken to assess why the person is still in bed. The following ECA rule schema informally represents this scenario: ON “person being in bed for a long period of time” IF “not expected to be in bed during this period” DO “contact relevant carer” Another example may be representation of a condition where the system knows a person is in their house, but when the doorbell has been activated by a visitor, the person in the house has not responded. This may be represented by the following ECA rule schema: ON “doorbell ringing and person not answering the call for a long time” IF “person inside house and not known to have hearing problems” DO “apply possible emergency plan” Here we have just provided schema rules. Notice that there are specific time-related concepts that are embedded in these rules, like the expression “a long period of time” in the first rule and the need to detect the temporal sequence between the doorbell ringing and the person not reacting to it. These concepts are domain dependant and should be further specified in a specific language that can be adequately interpreted by a computer, for example Prolog. To see one example of such a language, including temporal references like those depicted in Figure 3, and a specific application of the scenario described in this section to smart homes for elderly care, we invite the reader to make reference to Augusto and Nugent (2004). Through an ECA rule set specification it is possible to model the activities of the person and based on different activities the system can interact and change their living environment to promote independent living in a number of ways. The core element of such an interactive system will be reliant on an ADB management system hosted by an Internet-based server with capabilities to distinguish between normal situations and abnormal situations where some form of human intervention is required to assist the person. Example 2: Use of TR in Medication Management Medication compliance indicates the precision with which a patient follows a medical prescription. This is a relatively new research domain that is currently receiving much attention (Farmer, 1999; Wertheimer & Santella, 2003). Non-compliance has a negative impact on both the individual patient and the healthcare system and wider economy. The impact is clear: if a patient has been prescribed correctly following diagnosis, non- compliance becomes an important barrier in optimizing treatment. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Typically, compliance aids have been classified into three categories; pill holders (Corlett, 1996), alarm-based aids (Szeto & Giles, 1997) and monitoring devices (Wertheimer & Santella, 2003). For example, for a given patient, analysis of their data may show that due to their lifestyle they repeatedly miss their medication dosages on Friday afternoons and Saturday nights. For a different patient, analysis may show that they have high levels of non-compliance during periods at which they may be at work. The resultant informa- tion can be used to readjust the medication regimen in instances of non-compliance. Example 3: Hospital Management of Bed Occupancy The estimation of the length of stay of patients in hospitals is important for patient treatment management, bed occupancy management and cost effectiveness measures. Mathematical models have been produced as decision aids in this area (McClean, 1994) and in addition many trauma scores can be used to give an indication of patient survival probability (Boyd, Tolson, & Cope, 1987) and severity of trauma indices (Champion, Copes, & Sacco, 1990). All of this information along with demographic details, treatment, physical and mental scores can be taken into consideration and used as means upon which to generate a time to event measure, that is, prediction of length of stay in hospital. This is a complex and multi-factorial problem, but nevertheless one worthy of further attention. Qualitative and quantitative TR techniques may be used as the basis to model Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Management and Analysis of Time-Related Data in Internet-Based Healthcare 47 the time to event measures. These techniques can easily be integrated into a hospital based administrative system operating on an intranet/Internet basis which collates information from all in-patients and wards within a hospital environment, in addition to having access to centralized patient information. It can thus accommodate for the complex temporal nature of the problem through formalized approaches, for example: Quantitative TR Rule Set to Manage Bed Occupancy +Vacant beds should be increased by 10% during vacation periods, predicted flu epidemics etc. Future Trends It is clear that the Internet will have a long-term role within healthcare applications. At present its application and ability to improve upon current and existing healthcare practices has shown its promise and already we are slowly witnessing its uptake.

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This is commonly calculated in the generic The term apparent clearance is used because the drug industry to determine that the generic formulation bioavailability of the compound is unknown order 250 mg terramycin amex virus 552. Thus cheap 250mg terramycin overnight delivery antibiotic weight loss, bioavailability is not than the true systemic clearance because of this un- routinely calculated in an individual patient but re- known bioavailability. However, it is important to have an idea of how lated is that of renal clearance, or that portion of clear- formulations or routes of administration differ with re- ance that is due to renal elimination. Renal clearance is spect to bioavailability so as to allow proper dosage ad- calculated as: justment when changing formulations or routes of ad- Ae ministration. Calculation of renal clearance is Clearance is a pharmacokinetic parameter used to de- especially useful for drugs that are eliminated primarily scribe the efficiency of irreversible elimination of drug by the kidney. More specifically, clearance is defined as Because clearance estimates the efficiency of the the volume of blood from which drug can be completely body in eliminating drug, the calculation of clearance removed per unit of time (e. Clearance can involve both metabolism of drug to a Since this parameter includes both the volume of distri- metabolite and excretion of drug from the body. For ex- bution and the elimination rate, it adjusts for differences ample, a molecule that has undergone glucuronidation in distribution characteristics and elimination rates is described as having been cleared, even though the among people, thus permitting more accurate compar- molecule itself may not have left the body. However, as stated earlier, by drug can be accomplished by excretion of drug into the far the easiest clearance parameter to estimate is that of urine, gut contents, expired air, sweat, and saliva as well apparent (oral) clearance, since it does not require in- as metabolic conversion to another form. However, up- travenous administration, yet this parameter can be pro- take of drug into tissues does not constitute clearance. Total (systemic) Volume of Distribution clearance (Cl) can be calculated by either of the equa- tions given below: Vd relates a concentration of drug measured in the blood to the total amount of drug in the body. This Cl Vd ke mathematically determined value gives a rough indica- tion of the overall distribution of a drug in the body. In general, the greater the Vd, the greater where Vd is the volume of distribution (see below) and the diffusibility of the drug. One must give the drug intravenously to assure since its estimation may result in a volume greater than 100% bioavailability, because lack of 100% bioavail- the volume available in the body (~40 L in a 70-kg 52 I GENERAL PRINCIPLES OF PHARMACOLOGY adult). Following a single dose, concen- a highly lipid-soluble drug, such as thiopental, that can trations can be monitored until no longer analytically be extensively stored in fat depots may have a Vd con- detectable and a complete pharmacokinetic profile is siderably in excess of the entire fluid volume of the described. Thus, because of their physicochemical character- In clinical practice, drugs are more commonly ad- istics, different drugs can have quite different volumes ministered in multiple doses, with the second dose usu- of distribution in the same person. The final concen- drug does not distribute widely into tissues (though it trations of drug reached depend on the elimination rate does reach tissues to some degree to exert its action). In contrast, the time to reach steady widely throughout the body; in fact, it does distribute to state is affected by neither the dose amount nor dosing various tissues, such as the liver, lungs, eyes, and adipose frequency. Since the total volume of the body does not equal fected by the elimination rate (which is reflected in the 4200 L, it can clearly be seen that this is not a “real” vol- t1/2). Giving a larger dose or giving the dose more often ume but one that relates the blood concentration to the will not change the time needed to reach steady state amount of drug in the body. Just as it takes approximately five half-lives for a Protein Binding drug to be essentially (97%) eliminated, it also requires five half-lives for a drug to reach steady state. This is ex- Most drugs bind to plasma proteins such as albumin and emplified in the concentration–time profiles of Figure 1-acid glycoprotein (AGP) to some degree. The hypothetical drug in this example has a half-life comes clinically important as it is assumed that only un- of 8 hours and is dosed every 8 hours. The graph shows bound (free) drug is available for binding to receptors, that at about 40 hours (five half-lives), the maximum being metabolized by enzymes, and eliminated from the and minimum concentrations become consistent, indi- body. For example, phenytoin is approximately 90% bound to plasma proteins, leaving 10% of the concentration in the blood as free drug and available for pharmacologi- 1000 cal action and metabolism. If the presence of renal dis- ease or a drug interaction were to alter the degree of protein binding to only 80%, this change could have substantial clinical consequences. Even though the total t1/2 = 8hr percent bound changes relatively little, the net result is to double the amount of free drug. However, for most drugs, displacement from protein binding sites re- sults in only a transient increase in free drug concentra- tion, since the drug is rapidly redistributed into other body water compartments. Thus, interactions or changes 10 in protein binding in most cases have little clinical effect 0 despite these theoretical considerations.

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In initial episodes of genital herpes discount 250mg terramycin otc antibiotics enterococcus, oral acy- studies have demonstrated no teratogenic or embryo- clovir has been found to reduce viral shedding generic terramycin 250mg without prescription antibiotic resistant organisms, increase toxic effects of valacyclovir and acyclovir. Although the speed of healing of lesions, and decrease the dura- there are no large, controlled studies of the safety of tion of pain and new lesion formation. Acyclovir ap- these drugs in pregnant women, a prospective epidemi- pears to be less effective in the treatment of recurrent ological registry of acyclovir use during pregnancy herpes genitalis but may be used for the long-term sup- showed no increase in the incidence of common birth pression of recurrent HSV. Intravenous acyclovir is used in the treatment of The potential for drug interactions, particularly with herpes simplex encephalitis, neonatal HSV infection, other drugs that are actively secreted by the proximal and mucocutaneous HSV infection in immunocompro- tubules, should be considered. Cidofovir Acyclovir reduces the extent and duration of VZV lesions in adults and children, although higher doses are Cidofovir (Vistide) is an acyclic phosphonate cytosine required than for the treatment of HSV infection. It also inhibits of uncomplicated varicella in children, acyclovir may be adenoviruses, papillomaviruses, polyomaviruses, and used for chickenpox treatment and prophylaxis in high- poxviruses. Because this tients with herpes zoster (shingles), but it does not af- activation does not depend upon viral enzymes, similar fect postherpetic neuralgia. Cidofovir diphosphate competes with ceiving immunosuppressive drugs or cancer chemother- deoxycytidine triphosphate (dCTP) for access to viral 50 Antiviral Drugs 571 DNA polymerase and also acts as an alternative sub- ment. The incorporation of one cidofovir molecule into NSAIDs, amphotericin B, foscarnet) should not be the growing DNA chain slows replication; sequential in- given within 7 days of cidofovir administration. Docosanol Docosanol (Abreva) is a long-chain saturated alcohol Absorption, Metabolism, and Excretion that is clinically effective against HSV. It has in vitro ac- Cidofovir has extremely low oral bioavailability and so tivity against many enveloped viruses, including CMV, must be administered intravenously. Because it does not affect viral replication or pro- imately 87 hours and may serve as an intracellular tein production, it may be less susceptible to the develop- reservoir of the drug. Glomerular filtration and probenecid-sensitive tubular Absorption, Metabolism, and Excretion secretion are responsible for cidofovir elimination. Clinical Uses Cidofovir is approved for the treatment and prophy- Clinical Uses laxis of CMV retinitis in AIDS patients. It has also been Docosanol cream is approved for the over-the-counter used in the treatment of acyclovir-resistant (viral thymi- treatment of herpes labialis. It shortens the duration of dine kinase-deficient) HSV infections, polyomavirus- symptoms of cold sores and fever blisters but does not associated progressive multifocal leukoencephalopathy, provide symptomatic relief. Adverse Effects, Contraindications, and Drug Interactions Adverse Effects, Contraindications, and Drug Interactions Adverse effects of docosanol are minimal. Famciclovir (Famvir) is the diacetyl ester prodrug of the Probenecid is administered along with cidofovir to acyclic guanosine analogue 6-deoxypenciclovir (Dena- block its uptake into the proximal tubule epithelial cells vir). Penciclovir has activity against HSV-1, HSV-2, and thereby inhibit its tubular secretion as well as its VZV, and HBV. Acyclovir-resistant HSV strains levels of cidofovir causes cancer in rats; therefore, this that exhibit thymidine kinase deficiency are also resistant drug should be considered a potential human carcino- to famciclovir and penciclovir. Animal studies have also shown cidofovir to pro- duce embryotoxic and teratogenic effects and to impair Absorption, Metabolism, and Excretion fertility. Because of its potential nephrotoxicity, cidofovir Penciclovir is available as a topical cream; its absorption should not be used in individuals with renal impair- through the skin is undetectable. Famciclovir is well 572 VI CHEMOTHERAPY absorbed following oral administration and is rapidly different from that of other antiviral agents, cross- converted to penciclovir by hepatic first-pass metabo- resistance with other drugs used to treat CMV is unlikely. Fomivirsen is injected directly into the vitreous humor The plasma elimination half-life for penciclovir is 2 of the eye. Animal studies have shown that this drug ac- to 3 hours; however, the intracellular half-life of penci- cumulates in the retina and iris over 3 to 5 days and is clovir triphosphate is 7 to 20 hours in infected cells. Most penciclovir is eliminated unchanged by the kidney Fomivirsen exhibits minimal systemic absorption and is via glomerular filtration and active tubular secretion. Clinical Uses Clinical Uses Fomivirsen is used to treat CMV retinitis in patients with AIDS who have not responded to other treatments Penciclovir is approved as a topical formulation for the or in whom other treatments are contraindicated. In immunocompetent indi- pears to be at least as effective as other treatments and viduals, penciclovir shortens the duration of lesion pres- produces fewer side effects. Because CMV retinitis is ence and pain by approximately half a day when it is ini- often associated with CMV infection elsewhere in the tiated within an hour of lesion development and applied body, patients undergoing treatment with fomivirsen every 2 hours during waking hours for 4 days. Famciclovir is indicated for the treatment of acute herpes zoster (shingles); it is at least as effective in re- Adverse Effects, Contraindications, ducing pain and healing time.

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There are several other different applications for Licorice mint see Agastache light therapy cheap terramycin 250 mg amex virus 09, including: GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 1217 The patient sits in front of the box for a prescribed period of time (anywhere from 15 minutes to several hours) order terramycin 250mg online 3m antimicrobial filter. For patients just starting on the therapy, initial sessions are usually only 10–15 minutes in length. Some patients with SAD undergo light therapy session two or three times a day, others only once. The time of day and number of times treatment is administered depends on the physical needs and lifestyle of the individual patient. If light therapy has been prescribed for the treatment of SAD, it typically begins in the fall months as the days begin to shorten, and continues throughout the winter and possibly the early spring. Patients with a long-stand- ing history of SAD are usually able to establish a time- table or pattern to their depressive symptoms, and can initiate treatment accordingly before symptoms begin. The light from a slanted light box is designed to focus on the table it sits upon, so patients may look down to read or do other sedentary activities during therapy. Patients using an upright light box must face the light source, and should glance toward the light source occa- sionally without staring directly into the light. The light sources in these light boxes typically range from • Full-spectrum/UV light therapy for disorders of the 2,500–10,000 lux (in contrast, average indoor lighting is skin. A subtype of light therapy that is often prescribed 300–500 lux; a sunny summer day is about 100,000 lux). Some healthcare providers and healthcare supply very low-intensity beams of laser light on the skin, and companies also rent the fixtures. This gives a patient the is used in laser acupuncture to treat a myriad of symp- opportunity to have a trial run of the therapy before mak- toms and illnesses, including pain, stress, and tendinitis. Dawn simula- colored filters are applied over a light source to achieve tors are lighting devices or fixtures that are programmed specific therapeutic effects. The colored light is then to turn on gradually, from dim to bright light, to simulate focused on the patient, either with a floodlight which the sunrise. They are sometimes prescribed for individu- covers the patient with the colored light, or with a beam als who have difficulty getting up in the morning due to of light that is focused on the area of the illness. A 1998 report published in the designed to give an individual more mobility during treat- journal Science reported that the area behind the human ment. The visor is a lighting apparatus that is worn like a knee known as the popliteal region contains photoreceptors sun visor around the crown of the head. The history of eye problems should consult their healthcare authors of the study found that they could manipulate cir- professional before attempting to use a light visor. Further studies are needed to determine the efficacy Preparations of this treatment on disorders such as SAD and jet lag. Full-spectrum light boxes do emit UV rays, so patients with sun-sensitive skin should apply a sun screen before sit- Description ting in front of the box for an extended period of time. The most commonly used light therapy equipment is a portable lighting device known as a light box. The light box may be a Precautions full-spectrum box, in which the lighting element contains all Patients with eye problems should see an ophthal- wavelengths of light found in natural light (including UV mologist regularly both before and during light therapy. The box may be mount- taking photosensitizing medications should consult with ed upright to a wall, or slanted downwards towards a table. Depending on the condition, the colored light can be projected as a beam on a specific area or as a floodlight that covers the whole body. Cold laser Very low-intensity laser beams are directed at Used in laser acupunture to treat the body. A recent British study suggests that dawn simulation, a form of light therapy in Patients beginning light therapy for SAD may need which the patient is exposed to white light of gradually in- to adjust the length, frequency, and timing of their pho- creasing brightness (peaking at 250 lux after 90 min) may totherapy sessions in order to achieve the maximum ben- be even more effective in treating depression than exposure efits. However, such other light-related treatments as cold laser therapy and colored Side effects light therapy are not generally accepted, since few or no Some patients undergoing light therapy treatments scientific studies exist on the techniques. Most of these ef- Training & certification fects can be managed by adjusting the timing and dura- Psychiatrists, psychologists, and other mental tion of the light therapy sessions.

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