The Therapeutic Effect of Pancreatic Kininogenase on Treatment of Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes.

Background: To determine the therapeutic efficacy and cost-effective of pancreatic kininogenase (PKase) on treatment of diabetic peripheral neuropathy (DPN) compared with Prostaglandin E1 (PGE1) in patients with type 2 diabetes. Methods: 104 patients with DPN receiving standard glucose control therapy were randomly assigned into 3 groups: Group-A received PKase treatment, Group-B received PGE1 treatment, and Group-C received only standard glucose control therapy. Michigan neuropathy screening instrument (MNSI) score, neurophysiology examination, and nerve conduction velocity were measured. Results: Standard glucose control therapy significantly reduced hyperglycemia to a similar level in all groups. Questionnaire grading and neurophysiology examination both indicated that no significant difference was found at the end of treatment between Groups -A and -B. Except for the ulnar nerve sensory conduction velocity that was significantly improved in Group-B, the remaining nerve conduction velocity (regardless of sensory or motor nerve conduction velocities) was improved to a similar level in Groups -A and -B. Group-A had significantly reduced questionnaire grading and better improvement in motor nerve conduction velocity of the common peroneal nerve, ulnar nerve, and sensory nerve conduction velocity of the sural nerve as compared with Group-C. However, the medical cost of PKase was only 18.9% of that of PGE1 during one course of treatment. Conclusions: PKase has the similar therapeutic efficacy as PGE1 on treatment of DPN in patients with type 2 diabetes. However, the medical cost of PKase is one fifth of that of PGE1. Thus, PKase is a cost-effective drug for treatment of DPN.

Lubiprostone for chronic constipation in adults.

Lubiprostone (Amitiza-Sucampo Pharma Europe), a chloride-channel activator is licensed for the treatment of chronic idiopathic constipation in adults. It received a marketing authorisation in the UK in September 2012. In this article, we consider the evidence for lubiprostone in the management of constipation and how the treatment fits with current management strategies for constipation.

[Comparative pharmacoeconomic analysis of prostanoids for peripheral arterial occlusive].

Peripheral arteries occlusive disease (PAOD) is a prevalent illness that needs improved pharmacological management, especially for patients not eligible for surgical revascularization. Prostanoids (alprostadil or iloprost) were shown to be effective in PAOD and critical limb ischemia (CLI) but are rather costly. The results of our pharmacoeconomic study (cost estimation based on randomized control trial results) showed that iloprost does not increase cost of treatment when only direct medical costs are taken into account. If indirect costs are included into the analysis iloprost saves up to 27 thousand rubles per patient. Clinical efficacy is still high. Thus iloprost is a better alternative than alprostadil for CLI.

Cost-effectiveness of Liple (LipoPGE1) for arteriosclerosis obliterans patients in Japan: an economic evaluation using the EQ-5D instrument.

AIM: This study was conducted to evaluate the health-related quality of life (HRQOL) and cost-effectiveness of LipoPGE(1) when added to the conventional treatment of arteriosclerosis obliterans (ASO) patients. The research design consisted of a before and after-treatment study without comparison groups. We collected data from May 1999 through July 2001 at 473 institutions located throughout Japan. The subjects were ASO patients who experienced pain at rest or had ulcers of the extremities. METHODS: The observation period was a 2-month period that commenced with the start of administration of LipoPGE1. The HRQOL score (utility value) was obtained from the EQ-5D instrument, and the incremental cost-effectiveness ratio was calculated on the basis of quality-adjusted life years (QALYs). RESULTS: The mean utility value for the 2 months after the start of the administration of LipoPGE(1) was 0.672, and it was a significantly higher (P<0.0001) than the 0.616 before administration of LipoPGE(1). The incremental cost-effectiveness ratio was 18,807 US dollar/QALY assuming that drug efficacy persisted for 1 year after the end of LipoPGE1 therapy, and 75,227 dollar/QALY assuming a duration of just 3 months. CONCLUSIONS: We concluded that when LipoPGE1 is added to the conventional treatment of ASO patients, the HRQOL of the patient improves, and it is highly cost-effective.

Erectile dysfunction in spinal cord injury: a cost-utility analysis.

BACKGROUND: There is a high incidence of erectile dysfunction after spinal cord injury. This can have a profound effect on quality of life. Treatment options for erectile dysfunction include sildenafil, intracavernous injections of papaverine/alprostadil (Caverject), alprostadil/papaverine/phentolamine ("Triple Mix"), transurethral suppository (MUSE), surgically implanted prosthetic device and vacuum erection devices. However, physical impairments and accessibility may preclude patient self-utilization of non-oral treatments. METHODS: The costs and utilities of oral and non-oral erectile dysfunction treatments in a spinal cord injury population were examined in a cost-utility analysis conducted from a government payer perspective. Subjects with spinal cord injury (n=59) reported health preferences using the standard gamble technique. RESULTS: There was a higher health preference for oral therapy. The cost-effectiveness results indicated that sildenafil was the dominant economic strategy when compared with surgically implanted prosthetic devices, MUSE(R) and Caverject. The incremental cost-utility ratios comparing sildenafil with triple mix and vacuum erection devices favoured sildenafil, with ratios less than CAN$20,000 per quality adjusted life year gained. CONCLUSION: Based on this study, we conclude that sildenafil is a cost-effective treatment for erectile dysfunction in the spinal cord injury population.

[Vasaprostan in everyday practice of vascular surgery department]. / Vazaprostan v povsednevnoi praktike otdeleniia sosudistoi khirurgii.

The paper analyses vazaprostan administration to 88 patients with lower limb arteriosclerosis obliterans. Effectiveness of the drug is assessed in concordance with initial grade of ischemia.

[Treatment of severe intermittent claudication: ORACLE-PGE1 short term study. A randomised 40-week study. Evaluation of efficacy and costs]. / Trattamento della claudicatio intermittens severa: studio ORACLE-PGE1 short term. Registry e studio randomizzato a 40 settimane, valutazione di efficacia e costi.

BACKGROUND: The efficacy and cost of prostaglandin E1 (PGE1) in severe intermittent claudication was studied comparing a long-term protocol (LTP) with a short-term protocol (STP) in a randomised 40-week study. METHODS: Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. Treatment was performed with 2-hour infusions (60 micro g PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period), PGE1 was administered twice a week (same dosage). In phase 4 (40 weeks), no PGE1 were used. In STP, phase 2 treatment was performed in two days by a 2-hour infusion (60 micro g PGE1 twice a day in 2 days). The same cycle was repeated every 4 weeks. A treadmill test was performed at inclusion, at the beginning of each phase and at the end of weeks 12, 16, 20 32 and 40. A progressive training plan (walking) and reduction in risk factors plan was used in both groups. RESULTS: Out of the 1276 included patients 1165 completed the study (606 in LTP group; 559 in the STP). Drop-outs were 111. The two groups were comparable in distribution, risk factors and smoking. Intention-to-treat analysis indicated an increase in pain free walking distance (PFWD). The absolute and percent increase in pain-free walking distance (PFWD) was comparable in both LTP and STP groups with a significative increase in TWD at 4 weeks. At 20 and 40 weeks increase was up to 219% in the LTP and 460% in the STP group (p<0.02). Comparable results concerning PFWD were obtained in the two groups. Both treatments were well tolerated. No side effect was observed. Local effects were observed in 8.5% of the treated subjects in the LTP and 4% in the STP. The average cost of the LTP protocol was 8786 Euro. For STP the costs was 946 (10.8% of LTP). For both protocols the cost of the infusion was 24% of the total for the LTP and 35% in the STP. Therefore 75% of the cost is not drug-related. CONCLUSIONS: In conclusion between-group-analysis favours STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment particularly STP.

[Economic assessment of efficacy of vasaprostan treatment of critical lower limbs ischemia]. / Ekonomicheskaia otsenka éffektivnosti primeneniia vazaprostana pri kriticheskoi ishemii nizhnikh konechnostei.

AIM: To estimate cost-effect efficacy of vasaprostan treatment of inpatients with arterial chronic obliteration (ACO) with critical ischemia of the lower limbs (Fonten stage III-IV). MATERIAL AND METHODS: Case histories of 105 ACO patients with critical ischemia of the lower limbs (mean age 65 +/- 11.8 years) were analysed to compare efficacy and cost of the "typical practice" of hospital treatment of such patients with prognostic cost of basaprostan treatment using drug-cost modeling. RESULTS: The cost-effect analysis comparing efficacy of "typical practice" and vasaprostan treatment showed that in "typical practice" amputations of the limb are inevitable in 41% while vasaprostan treatment reduces the percentage of the operations to 8.6-12% (according to the literature); overall cost of the "typical" treatment for 105 patients reached 3,909,222 roubles while relevant prognostic cost of vasaprostan treatment made up 4,407,162-4,570,653 roubles. Thus, vasaprostan treatment is characterized by less expense per 1 case of the limb amputation prevention vs "typical practice". CONCLUSION: The models used demonstrated that vasaprostan treatment is more cost-effective than "typical practice".

Prostaglandin E1 versus sex therapy in the management of psychogenic erectile dysfunction.

The treatment for psychogenic erectile dysfunction has been previously managed by non-medical methods consisting of counseling with a psychiatrist, psychologist or sex therapist. The success rate for treatment with counseling has not been uniformly successful. This paper compares the treatment of psychogenic erectile dysfunction using standard sex therapy and self-injection therapy using low-dose PGE1. Fifty men with psychogenic impotence were divided into two groups: standard sex therapy for twelve weeks or treatment using low-dose (2.5 - 5.0 microg) of PGE1. The results showed that men treated with low-dose PGE1 had a 47% improvement of obtaining an unaided erection compared to 58% improvement rate with sex therapy. 69% of patients in the PGE1 group were satisfied with their treatment compared to 75% receiving sex therapy. The frequency of intercourse reported in patient diaries for the two groups was similar (20.5 per month for PGE1 vs 20.0 per month for sex therapy. The reported duration of erection by patients receiving PGE1 therapy was longer than that reported by those receiving sex therapy (35 min vs 10 min). The comparison of the cost of treatment of the two treatment groups reveals that the sex therapy is approximately 25% more expensive than the PGE1 treatment. This pilot study demonstrates that the efficacy of PGE1 was numerically, though not statistically, less than sex therapy in the treatment of psychogenic impotence. The cost per positive outcome with PGE1 treatment is lower than that of sex therapy treatment making PGE1 more cost-effective.

Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study.

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.

PGE(1) treatment of severe intermittent claudication (short-term versus long-term, associated with exercise)--efficacy and costs in a 20-week, randomized trial.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon 40 microg; second day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 microg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p<0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the STP group (147% difference; p<0.02). The increase in TWD was 368% in the LTP group and 529% in the STP group (161% difference; p<0.02). In both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks, but results obtained with STP are better considering both walking distances. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average cost of LTP was 6,664 Euro; for STP the average costs was approximately 1,820 E. The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the LTP and 8.5 E with the STP (18% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,989 E vs. 421 E with STP (p<0.02). Between-group analysis favors STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE, treatment. With STP less time is spent in infusion and more in the exercise program. STP reduces costs, speeds rehabilitation, and may be easily used in a larger number of nonspecialized units.

Treatment of severe intermittent claudication with PGE1--a short-term vs a long-term infusion plan--a 20 week, European randomized trial--analysis of efficacy and costs.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied by comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 109 patients (96 completed the study) with an average total walking distance of 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks). In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP, phase 2 treatment was performed in 2 days by a 2-hour infusion (1st day: morning 20 microg, afternoon 40 microg; 2nd day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate reduced tolerability or side effects. Full dosage (60 microg b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of the 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% STP vs 107.3% LTP), and at 20 weeks (351% STP vs 242% LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. Average cost of LTP was approximately 6,588 ECU; for STP the average cost was approximately 1,881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,937 ECU vs 550 ECU with STP (p<0.02). The cost of PGE1 (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). In summary, between-group-analysis favors STP, in terms of walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation, and may be used in a larger number of nonspecialized units available to follow the protocol.

Comparative study of intravaginal misoprostol with gemeprost as an abortifacient in second trimester missed abortion.

This prospective, randomized study compared the efficacy of intravaginal misoprostol (Cytotec) and gemeprost (Cervagem) as an abortifacient for intrauterine deaths in second trimester pregnancy. Side-effects, complications and the cost-effectiveness associated with each drug were assessed. 21 out of 25 patients (84%) in the misoprostol group aborted whereas only 17 out of 25 patients (68%) in the gemeprost group aborted within 24 hours after the initiation of therapy. In the misoprostol group, the abortion rate was influenced by the gestational age with 100% abortion rate for those > 17 weeks' gestation compared to 67% for those with a gestational age of 13-16 weeks. Side-effects were rare in either group and no major complications were reported in either group. Misoprostol was definitely more cost-effective compared to gemeprost as the mean cost of inducing an abortion using misoprostol was RM 1.08 whereas that of gemeprost was RM 105. We thus concluded that misoprostol was at least as effective as gemeprost as an abortifacient for intrauterine death in second trimester pregnancy. Moreover, it was less costly, with very few side-effects.

PIP: The efficacy of intravaginal misoprostol (Cytotec) and gemeprost (Cervagem) as abortifacients in second-trimester pregnancies was compared in a prospective study of 50 women admitted to Hospital Kuala Lumpur (Malaysia) with an intrauterine death at a gestational age of 13-26 weeks. 25 women were randomly assigned to receive 200 mcg of misoprostol inserted into the posterior fornix of the vagina every 3 hours until abortion occurred; the remaining 25 women received 1 mg of gemeprost every 3 hours until abortion. Within 24 hours of drug administration, 21 women (84%) in the misoprostol group and 17 (68%) in the gemeprost group had aborted. In the misoprostol group, the abortion rate was influenced by gestational age; this rate was 100% in women with pregnancies over 17 weeks' gestation compared with 67% in women in weeks 13-16. No major side effects or complications occurred in either group. The mean cost of abortion induction was RM 1.08 with misoprostol and RM 105 with gemeprost. Misoprostol seems to be the drug of choice for second-trimester pregnancy termination. Not only is intravaginal misoprostol at least as effective as gemeprost, it is less costly, does not require refrigeration for storage, and is associated with few side effects. Additional studies with larger sample sizes are recommended to determine the optimal misoprostol dosage and frequency of administration.

A cost analysis of alprostadil in liver transplantation.

Alprostadil (prostaglandin E1) administration to liver transplant recipients has been shown to result in a significant reduction in the duration of hospital admission for transplantation, and in the need for re-operations (other than re-transplants) and renal support. To study the economic impact of this finding, we examined data from a controlled trial for all single-transplant surviving patients (42 alprostadil, 49 controls) for whom complete billing records were available for transplant days -2 to +150. All costs were measured in 1992 US dollars. Patients given alprostadil had lower total charges [mean +/- standard deviation (SD) $US175 297 +/- $US70 652] than patients given placebo (mean +/- SD $US225 672 +/- $US187 208) [p = 0.043]. The data suggest that the use of alprostadil may have a significant favourable impact on the cost of liver transplantation.

Medical abortion in Britain.

PIP: Factors affecting method preference for induced abortion in Britain are cost and experience in clinical trials. Demand for abortion exists regardless of access to contraception; 1 in 5 pregnancies in Britain are aborted. Since July 1991, alternatives to vacuum aspiration have become available. RU486, or mifepristone, in combination with gemeprost, a prostaglandin, 48 hours later has shown a 95% successful complete abortion rate. The actual study involve 100 women at 9 weeks' gestation receiving 600 mg of mifepristone followed by 1 mg of gemeprost pessary. The complication rate was low and the pregnancy continuation rate was 0.3% which is similar to vacuum aspiration. Almost 50% of abortion seekers in France prefer medical (drug-induced) abortions. Studies in Aberdeen have shown that about 25% desired either medical or surgical abortion and 50% had no preference. Only about 10% of abortions performed in Britain are medical abortions. The reasons medical abortion is not more widely used, regardless of its availability, may involve the organization of services for abortion: the requirement for prompt referral before 9 weeks, the special licensing required for practice of medical abortion on the premises, and higher cost. Medical abortions cost 43 pounds for the mifepristone and 21 pounds for the gemeprost, but the cost could be reduced by reducing the amount of mifepristone to 200 or 400 mg in combination with 0.5 or 1 mg of gemeprost. World Health Organization studies have found little loss in efficacy and a significant reduction in diarrhea and vomiting, which, with the reduction in cost, ought to make medical abortion more attractive to women and institutions. Studies in France an the United Kingdom have found that a synthetic prostaglandin, misoprostol, could be substituted for gemeprost and reduce the side effects associated with gemeprost. Misoprostol also costs only 1 pound for a 400-600 mg dose. Medical abortion has the advantage of not requiring highly skilled staff or special facilities; the necessary room should have couches or beds. 2 trained nurses under medical supervision could serve 6 women per morning. Three visits are required. Most of the present use is in hospitals in the UK that have conducted clinical trials.^ieng

Experience with intracavernosal tri-mixture for the management of neurogenic erectile dysfunction.

Using papaverine, papaverine/phentolamine, or prostaglandin E1 (PGE1), intracavernosal pharmacotherapy has been successful in treating erectile dysfunction. The limiting factor of using these medicines is intracorporeal fibrosis with the first two and a high cost with PGE1. Our experience with intracavernosal therapy in patients with impotence secondary to neurogenic disease has included 35 men, 30 of whom are spinal cord injured, 3 after radical prostatectomy, 1 with multiple sclerosis, and 1 with lower extremity weakness after surgery. Patients ranged in age from 22 to 59 years, with an average of 36.3 years; mean follow-up was 13.8 months. Intracavernosal therapy has been performed with a tri-mixture of papaverine hydrochloride (smooth muscle relaxant), phentolamine mesylate (alpha-adrenergic blocking agent) and alprostadil (PGE1- a vasodilator and smooth muscle relaxant). Of the patient population, all 35 patients were able to have adequate erections for sexual relations with minimal complications. Acting synergistically, the ingredients promote erectile activity using small doses and without a significant incidence of priapism or fibrosis. Techniques of injection, dosing and followup are discussed.