Clinical benefit

As a result of such studies hypertension has been operationally defined as the blood pressure level above which therapeutic intervention has clinical benefit. As increasingly aggressive intervention has continued to demonstrate benefits, this level has gradually reduced over time and is commonly defined as systolic blood pressure>l40 mmHg and/or diastolic blood pressure >90 mmHg (Table 1). Isolated systolic hypertension is defined as systolic blood pressure >140 mmHg and diastolic blood pressure <90 mmHg. 

The PAR family represents a novel target for drug therapy. Therapeutic approaches with most clinical benefit may rely upon the development of both agonists and antagonists, either of which could be utilised dqiending upon the disease condition [3]. 

TK NK2r antagonists showed interesting activities in preclinical models of depression, anxiety, asthma, gastrointestinal dysmotility and hypersensitivity, and urinary incontinence [1,3]. In clinical, NK2r antagonists antagonize NKA-induced bronchoconstriction and NKA-induced intestinal dysmotility. However, a pilot trial in asthma failed to show any clinical benefit by... 

VEGF inhibitors have demonstrated a marked clinical benefit also in wet AMD. Blockade of all VEGF-A isoforms and bioactive fragmemts with ranibizumab not only slowed down vision loss, but unexpectedly appears to have the potential to enable many AMD patients to obtain a meaningful and sustained gain of vision. Further research is needed to determine whether the vision gain conferred by ranibizumab extends beyond 24 months and whether additional intraocular neovascular syndromes may benefit from this treatment. 

Muller H, Michoux N, Bandon D, Geissbuhler A. A review of content-based image retrieval systems in medical applications—clinical benefits and future directions. International Journal of Medical Informatics 2004 73 1-23. 

In addition, the approximately 1-2% risk of peristroke myocardial infarction was shghtly reduced, which increased the net clinical benefit of 9 per 1000 to about 10 favorable outcomes per 1000 treated. 

The first proper double blind trial of embryonic implants in 40 PD patients (20 undergoing just surgery without any implant), has shown no improvement in patients over 60 years but some clinical benefit (fewer symptoms between levodopa dosing) in those below that age. Unfortunately some of these responders eventually developed dyskinesias, a sign of too much dopamine, and further implants were halted until the technique has been re-evaluated, see Freed, CR et al. N EnglJ Med 2001, 344 710-719. 

Recommendations in this section may change based on the results from the recent EPO-3 trial (epoetin alfa versus placebo). A difference in red blood cell transfusion rates was not observed between groups. Epoetin alpha therapy improved survival in trauma patients. Epoetin alfa did not have a measurable clinical benefit in medical/surgical non-trauma patients. Epoetin alpha therapy was associated with an increased thrombotic event rate, particularly in patients not receiving pharmacological deep vein thrombosis prophylaxis. 

Treatment should begin as early as possible in patients with a diagnosis of AD.30 Figure 32-2 provides a recommended treatment algorithm for AD.31 Patients should be switched to another ChE inhibitor from their initial ChE inhibitor if they show an initial lack of efficacy initially respond to treatment, but lose clinical benefit or experience safety/tolerability issues. This switch should not be attempted until the patient has been on a maximally tolerated dose for a period of 3 to 6 months. The switch should also be based on realistic expectations of the patient and/or caregiver.32 ChE inhibitor therapy should be discontinued in patients who experience poor tolerance or compliance, who show a lack of clinical improvement after 3 to 6 months at optimal dosing, who continue to deteriorate at the pretreatment rate, or who demonstrate dramatic clinical deterioration following initiation of treatment.33... 

Galantamine is a ChE inhibitor, which elevates acetylcholine in the cerebral cortex by slowing the degradation of acetylcholine.37 It also modulates the nicotinic acetylcholine receptors to increase acetylcholine from surviving presynaptic nerve terminals. In addition, it may increase glutamate and serotonin levels. The clinical benefit of action of these additional neurotransmitters is unknown. 

While the exact mechanism of action remains unclear, dacarbazine appears to inhibit DNA, RNA, and protein synthesis. Dacarbazine disappears rapidly from the plasma, with a terminal half-life of about 40 minutes. Dacarbazine has shown clinical benefit in the treatment of melanoma, Hodgkin s lymphoma, and soft tissue sarcomas. Side effects include myelosuppression, severe nausea and vomiting, and a flulike syndrome that starts about 7 days after treatment and lasts 1 to 3 weeks. 

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