High-Cost Cancer Treatment Across Borders in Conflict Zones: Experience of Iraqi Patients in Lebanon.

PURPOSE: Conflict-induced cross-border travel for medical treatment is commonly observed in the Middle East. There has been little research conducted on the financial impact this has on patients with cancer or on how cancer centers can adapt their services to meet the needs of this population. This study examines the experience of Iraqi patients seeking care in Lebanon, aiming to understand the social and financial contexts of conflict-related cross-border travel for cancer diagnosis and treatment. PATIENTS AND METHODS: After institutional review board approval, 60 Iraqi patients and caregivers seeking cancer care at a major tertiary referral center in Lebanon were interviewed. RESULTS: Fifty-four respondents (90%) reported high levels of financial distress. Patients relied on the sale of possessions (48%), the sale of homes (30%), and vast networks to raise funds for treatment. Thematic analysis revealed several key drivers for undergoing cross-border treatment, including the conflict-driven exodus of Iraqi oncology specialists; the destruction of hospitals or road blockages; referrals by Iraqi physicians to Lebanese hospitals; the geographic proximity of Lebanon; and the lack of diagnostic equipment, radiotherapy machines, and reliable provision of chemotherapy in Iraqi hospitals. CONCLUSION: As a phenomenon distinct from medical tourism, conflict-related deficiencies in health care at home force patients with limited financial resources to undergo cancer treatment in neighboring countries. We highlight the importance of shared decision making and consider the unique socioeconomic status of this population of patients when planning treatment.

Dose-effect relationship of the beta-agonists fenoterol and salbutamol in patients with asthma.

QUESTION: What is the relative per microgram potency and side effect profile of the beta-agonists salbutamol and fenoterol? METHOD: The relative bronchodilator (delta FEV1, V25, V50) potency and side effect profile (delta tremor, heart rate, breathlessness, BP) of nebulized salbutamol and fenoterol were evaluated by means of a randomized, double-blind, crossover, cumulative (50 to 2,500 micrograms) dose-response study. Both beta-agonists were administered to 12 patients with stable asthma over age 18 years with baseline FEV1 between 35 to 70 percent predicted. RESULTS: (1) Salbutamol and fenoterol both provided significant bronchodilatation compared with baseline. (2) There was no dose-effect difference between the two beta-agonists with respect to bronchodilator response. (3) Overall there was no significant difference between the side effect profiles of the two beta-agonists, although at the highest dose of fenoterol, there was marginally greater tremor when measured by accelerometry. (4) There was no difference in the vital signs or subjective patient evaluations of tremor, palpitations, or breathlessness as estimated by a visual analogue scale. (5) No significant adverse reactions occurred. SUMMARY AND CONCLUSION: Equivalent bronchodilatation and similar side effect profiles were measured in a group of patients with stable asthma after treatment with nebulized salbutamol or fenoterol in the dose range 50 to 1,250 micrograms (cumulative, 2,500 micrograms). This indicates that both beta-agonists have similar per microgram potency and side effect profiles. Observed clinical differences in response or side effects associated with fenoterol metered-dose inhaler administration may be a result of its higher dose per puff metered-dose inhaler formulation.

Definition and measurement of restenosis after successful coronary angioplasty: implications for clinical trials.

Angiographic restenosis represents the most established measure of long-term outcome in most prospective clinical trials of coronary angioplasty (PTCA). The accuracy of assessing this endpoint is of utmost importance. The purpose of this article is to propose guidelines for the use of coronary angiography in this setting. First, the cineangiograms must be of high technical quality and performed in a high proportion of consecutive patients in follow-up under controlled study conditions that are reproducible. Second, computer-assisted quantitative coronary angiographic analysis is essential to minimize interobserver and intraobserver variability in stenosis measurement between successive studies. The following recommendations are presented for quantitative coronary angiographic analysis. Because biplane orthogonal views cannot always be performed both at baseline and at follow-up, stenosis measurement in the single-plane, most severe view often constitutes the most consistent and practical approach. The edge-detection method is still much more reproducible and accurate than densitometry and should be the preferred method of analysis. Measurement of reference diameter by the interpolated method is more objective than measurement by the user-defined approach and should be used whenever possible. Finally, measurements of absolute minimum diameter and percent diameter stenosis are both important in the assessment of outcome in clinical trials. Absolute minimum diameters are independent of variations in reference diameter, and the extent of reduction in minimum diameter between the immediate postangioplasty and follow-up angiograms, when expressed in dichotomous or continuous fashion, accurately defines the extent of vessel wall hyperplasia as an endpoint. On the other hand, vessel size corresponds in general to the size of myocardium subserved, and absolute changes do not take into account this physiologic fact. Therefore defining restenosis in terms of significant reduction in percent diameter stenosis is also a useful approach because of its clinical relevance. Thus clinical restenosis requires that a successfully dilated segment (< 50% diameter stenosis) show a > or = 50% diameter stenosis at follow-up angiography with, in addition, a meaningful degree of change, that is, exceeding 2 SDs of observer variability in quantitative measurements which, in our experience, translates into > or = 15% difference between early postangioplasty and follow-up angiography measurements.

Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty.

In a recent prospective double-blind placebo-controlled trial, a combination of aspirin and dipyridamole was not associated with a reduction in the rate of restenosis within the 1st 6 months after coronary angioplasty. The purpose of this study was to determine whether clinical, anatomic or procedural factors were predictive of the observed restenosis rates in that prospective trial. A total of 247 patients and 280 segments underwent follow-up angiography and quantitative coronary angiographic analysis between 4 and 7 months after coronary angioplasty. Two baseline clinical characteristics--angina class and duration of angina in months--were related to the rate of restenosis by univariate analysis. Patient-related stepwise logistic regression analysis identified severity of angina as the only clinical predictor of restenosis. Three univariate baseline anatomic characteristics--percent diameter stenosis before angioplasty, stenosis greater than 10 mm in length and calcific stenosis--and two early postangioplasty characteristics--residual percent diameter stenosis and residual mean pressure gradient--were predictive of restenosis. Of these, only two--length of stenosis and residual percent diameter stenosis--were independently related to restenosis by multivariate analysis and only the former is identifiable before the procedure. It is concluded that in prospective studies in contrast to retrospective studies, few clinical and anatomic factors appear to be predictive of restenosis after coronary angioplasty.

The role of antiplatelet agents in modifying the extent of restenosis following percutaneous transluminal coronary angioplasty.

We previously reported that a combination of aspirin and dipyridamole given before, during, and for 6 months following percutaneous transluminal coronary angioplasty (PTCA) did not reduce the incidence of restenosis. In that trial, a total of 272 successfully dilated segments in 243 patients reached final quantitative angiography and of these, 86 segments (31.6%) had restenosed (46 of 130 segments in the group of patients given placebo and 40 of 142 segments in the aspirin-dipyridamole group). A secondary analysis of these 86 segments revealed that at follow-up angiography the severity of restenosis was greater in the 46 segments in the placebo group than in the 40 segments in the active treatment group (mean minimal luminal diameter at the stenosis = 0.76 +/- 0.52 and 1.03 +/- 0.45 mm, respectively, p = 0.01). The frequency of total or subtotal occlusions was higher in the placebo group (17.4%) than in the active treatment group (5.0%), but this observation did not reach statistical significance (p = 0.07). Although long-term treatment with aspirin and dipyridamole after successful PTCA does not reduce the incidence of recurrence, this secondary analysis suggests that it is associated with a decreased likelihood of severe restenosis.

Prevention of acute complications after percutaneous transluminal coronary angioplasty.

The prevention of major complications occurring during or early after percutaneous transluminal coronary angioplasty was evaluated in 376 patients in a randomized, double-blind, placebo-controlled multicenter trial. Starting 24 hours before angioplasty, 187 patients received an aspirin-dipyridamole combination and 189 were given placebo. There were no periprocedural deaths. Periprocedural non-fatal myocardial infarction was diagnosed in 34 patients (9.0%). Q wave myocardial infarction occurred in 16 patients: 3 (1.6%) in the aspirin-dipyridamole group and 13 (6.9%) in the placebo group (p = 0.0113). Non-Q wave myocardial infarction occurred in 18 patients: 6 (3.2%) in the active drug group and 12 (6.3%) in the placebo group (p = 0.1538). Emergency myocardial revascularization was performed in 9 patients in each treatment arm. Q wave myocardial infarction occurred following revascularization in 5 patients (55.5%) in the placebo group and in only 2 (22.2%, p = 0.1670) in the aspirin-dipyridamole group. Thus the incidence of periprocedural Q and non-Q wave myocardial infarction is high in patients not on antiplatelet therapy (13.2%) and is markedly lower in those on the aspirin-dipyridamole combination (4.8%, p = 0.0044). Short-term antiplatelet therapy before and after angioplasty can be recommended for patients who do not have contraindications to this medication.

Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty.

To examine the role of antiplatelet therapy in the prevention of arterial restenosis after percutaneous transluminal coronary angioplasty (PTCA), we conducted a randomized, double-blind, placebo-controlled study in 376 patients. The active treatment consisted of an oral aspirin-dipyridamole combination (330 mg-75 mg) given three times daily, beginning 24 hours before PTCA. Eight hours before PTCA, the oral dipyridamole was replaced with intravenous dipyridamole at a dosage of 10 mg per hour for 24 hours, and oral aspirin was continued. Sixteen hours after PTCA, the initial combination was reinstituted. Treatment was continued in patients with a successfully dilated vessel until follow-up angiography four to seven months after PTCA--or earlier, if symptoms dictated. Of 249 patients who underwent follow-up angiography, 37.7 percent of patients receiving the active drug had restenosis in at least one segment, as compared with 38.6 percent of patients taking placebo (P not significant). The number of stenotic segments was virtually the same in the two groups. Among the 376 randomized patients, there were 16 periprocedural Q-wave myocardial infarctions--13 in the placebo group and 3 in the active-drug group (6.9 percent vs. 1.6 percent, P = 0.0113). Although the use of this antiplatelet regimen before and after PTCA did not reduce the six-month rate of restenosis after successful coronary angioplasty, it markedly reduced the incidence of transmural myocardial infarction during or soon after PTCA. Thus, the short-term use of antiplatelet agents in relation to PTCA can be recommended.

Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children.

A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma. A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide. Twenty-five children ranging in age from 5 to 15 years were enrolled in the study. Children with FEV1 less than or equal to 55% predicted were eligible to participate in the study. Subjects were randomized in a double-blind fashion into one of two treatment groups. Both groups received an initial dose of salbutamol by nebulizer of 150 micrograms/kg (0.03 cc/kg), followed by six consecutive doses of 50 micrograms/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 micrograms (1.0 ml) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation, and at 40 and 80 minutes, whereas the remaining subjects received a placebo with salbutamol at those times. Formal one-way statistical ANOVA with change in percent predicted FEV1 as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period. There was no significant difference in side effects reported in the two groups. Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group.

A controlled trial of ambroxol in chronic bronchitis.

Ambroxol is a mucolytic agent which is widely used in chronic bronchitis in Europe. We conducted a double-blind randomized controlled trial of ambroxol vs matched placebo in 90 patients with chronic bronchitis and difficulty clearing secretions. It was concluded that there was no advantage to taking ambroxol.

Control of the hypersecretion of vasomotor rhinitis by topical ipratropium bromide.

A randomized, double-blind, placebo-controlled trial of ipratropium bromide nasal spray was performed with 25 patients with vasomotor rhinitis. Criteria for selection of patients were (1) clear watery nasal discharge more than 1 hour each day, (2) absent or mild nasal obstruction, (3) no known allergic cause, and (4) no satisfactory response to previous alternative medications. Ipratropium bromide, two sprays (20 micrograms per spray) in each nasal cavity four times daily, for 3 weeks, produced a major reduction in nasal discharge severity and duration (p less than 0.00005 for daytime reduction in both). There was a decreased daily use of nasal tissues (p = 0.0017). At the end of the trial, 21 patients preferred the drug, two preferred placebo, one had no preference, and one patient dropped out for a reason unrelated to symptoms or treatment. This drug preference in favor of active medication was statistically significant at the 0.01 level. Local mild side effects were reported in 21/25 (84%) with ipratropium bromide and 8/25 (32%) with placebo (p = 0.0004). Pulse and blood pressure were not affected. In an ensuing 1-year open trial in which the frequency of use of ipratropium bromide nasal spray was selected by the subjects, the dosage chosen was considerably lower than that used in the controlled trial. There were seven dropouts caused by insufficient benefit or local side effects. Seventeen subjects continued the use of ipratropium bromide for 1 year and reported good results and no side effects. Topical nasal ipratropium bromide is highly effective in the control of the rhinorrhea of vasomotor rhinitis. Drug dosage is a major determinant of local nasal side effects.

Preservation of platelets and blood products by intravenously administered dipyridamole in patients who undergo coronary artery bypass grafting.

The combination of dipyridamole and acetylsalicylic acid has been proven effective in preventing coronary artery bypass graft occlusion, but the benefits of dipyridamole alone have not yet been evaluated. In order to assess the value of dipyridamole alone, the authors randomized 24 patients (age range from 47 to 76 years) who underwent coronary artery bypass grafting to treatment with either dipyridamole (120 mg/d) by constant intravenous infusion or isotonic dextrose solution. They recorded platelet counts and aggregates, hemoglobin levels, total blood loss, blood products and intravenous fluids given and dipyridamole plasma levels, starting 8 hours before operation and continuing for 3 days after. The two groups were similar with respect to pump time, cross-clamp time and baseline demographic factors. Platelet counts during cross-clamping and 1 hour postoperatively were similar, but those on days 1, 2 and 3 postoperatively were significantly (p = 0.01 to 0.02) higher in the dipyridamole group. Mean blood losses in this group were 22% to 30% lower, but the difference was not significant. However, administration of erythrocytes and plasma was 49% to 58% less in the dipyridamole group (p = 0.005 to 0.048) over the same period. Dipyridamole plasma concentrations varied from 0.37 micrograms/ml before and during bypass to 1.5 micrograms/ml in the 3 days after. The authors conclude that dipyridamole administered intravenously to patients who undergo coronary artery bypass grafting may preserve hemostatically effective platelets so that fewer blood products are required.

A trial of intranasal Atrovent versus placebo in the treatment of vasomotor rhinitis.

Twenty-six patients with perennial rhinorrhea were treated by Atrovent, the anticholinergic agent, or placebo in a randomized double-blind crossover trial. The severity and duration of rhinorrhea were significantly reduced by Atrovent. Local side effects were more frequent with the active drug. These were reduced in a later open trial by a reduction in dosage.

Dose-response characteristics of nebulized fenoterol in asthmatic children.

Fenoterol hydrobromide, a beta 2-selective bronchodilator, was administered by aqueous nebulization to 31 children with stable asthma. An initial comparison of 0, 100, 300, and 1000 micrograms drug in 20 of these patients showed a significant change in forced expiratory volume in 1 second for all three doses compared with change after placebo (P less than 0.0001). However, the differences in peak pulmonary response from 100 to 1000 micrograms were not large (P greater than 0.2). Assessment of spirometric responses of 11 children to 3, 10, 30, or 100 micrograms nebulized fenoterol clearly revealed the dose-response effect (P less than 0.01). When all the FEV1 data were plotted over the entire range of 3 to 1000 micrograms, the resultant log dose vs response curve could be characterized by the ED50, the amount of drug producing half-maximal response. At 15, 30, or 60 minutes, the ED50 was in the range 8 to 10 micrograms. With increasing time there was a parallel shift of the entire dose response curve to the right, manifested by ED50 of 47 and 150 micrograms at two and three hours, respectively, after administration. This decreasing potency of a sympathomimetic drug with time shows that duration of effect and dosage are interdependent variables and must be evaluated simultaneously. Such considerations cannot be derived from cumulative dose-response studies. In our patients, 100 to 300 micrograms fenoterol delivered by aqueous nebulization achieved optimal bronchodilation with no detectable cardiovascular side effects.

Prognostic factors in T3 glottic cancer.

A detailed statistical analysis of prognostic factors influencing the local control rate by irradiation in T3 glottic cancer is presented. This has been done to identify favorable and unfavorable prognostic factors in order to precisely identify areas where new treatment strategies are needed. Between 1963 and 1977, 110 patients with T3NOMO glottic cancer were treated with radical radiotherapy with surgery for salvage. Only one of 12 women recurred following irradiation compared with 50 recurrences so far among the 98 men (P = 0.006). The recurrence rate among men using an NSD of less than 1700 rets was significantly higher than when an NSD of greater than 1700 rets was used (P = 0.022). This difference remained significant even after correction for other possible confounding variables. The recurrence rate among men over the age of 60 years was significantly lower than in men under 60 (P = 0.022). This difference in local control is due to a high proportion of patients with residual disease following irradiation. Factors not found to be of significance included radiation field size, superficial extent of disease, and tracheostomy before or during treatment. No difference in surgical salvage between the residual and recurrent disease cases has been seen. The cause of failure to respond to irradiation is discussed and possible ways to improve the local control by irradiation, particularly in young males, are suggested.