A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions

A Randomized Comparison of Indwelling Pleural
Catheter and Doxycycline Pleurodesis in the
Management of Malignant Pleural Effusions

Joe B. Putnam, Jr.,
BACKGROUND. The purpose of this study was to compare the effectiveness and
Richard W. Light,
safety of a chronic indwelling pleural catheter with doxycycline pleurodesis via R. Michael Rodriguez,
tube thoracostomy in the treatment of patients with recurrent symptomatic ma- Ronald Ponn,
Jemi Olak,
METHODS. In this multi-institutional study conducted between March 1994 and
Jeffrey S. Pollak,
February 1997, 144 patients (61 men and 83 women) were randomized in a 2:1 Robert B. Lee,
distribution to either an indwelling pleural catheter or doxycycline pleurodesis.
D. Keith Payne,
Patients receiving the indwelling catheter drained their effusions via vacuum Geoff Graeber,
bottles every other day or as needed for relief of dyspnea.
Kevin L. Kovitz,
RESULTS. The median hospitalization time was 1.0 day for the catheter group and
6.5 days for the doxycycline group. The degree of symptomatic improvement in
1 Department of Thoracic and Cardiovascular Sur- dyspnea and the quality of life was comparable in each group. Six of 28 patients gery, the University of Texas M. D. Anderson Can-cer Center, Houston, Texas.
who received doxycycline (21%) had a late recurrence of pleural effusion, whereas 12 of 91 patients who had an indwelling catheter (13%) had a late recurrence of Department of Medicine, Saint Thomas Hospital and Vanderbilt University, Nashville, Tennessee.
their effusions or a blockage of their catheter after the initially successful treatment (P ϭ 0.446). Of the 91 patients sent home with the pleural catheter, 42 (46%) Department of Surgery, Hospital of Saint Raphael and Yale University, New Haven, Connecticut.
achieved spontaneous pleurodesis at a median of 26.5 days.
A chronic indwelling pleural catheter is an effective treatment for Department of Surgery, University of Chicago, the management of patients with symptomatic, recurrent, malignant pleural effu- sions. When compared with doxycycline pleurodesis via tube thoracostomy, the Department of Radiology, Yale University School of Medicine, New Haven, Connecticut.
pleural catheter requires a shorter hospitalization and can be placed and managed on an outpatient basis. Cancer 1999;86:1992–9.
Department of Surgery, Emory University, At- 7 Department of Medicine, Louisiana State Univer-sity Medical Center, Shreveport, Louisiana.
KEYWORDS: malignant pleural effusion, pleurodesis, indwelling catheter.
8 Department of Surgery, West Virginia University,Morgantown, West Virginia.
Management of the patient with a symptomatic malignant pleural
9 Department of Medicine, Tulane University, New effusion (MPE) remains problematic. The current management of MPE entails the production of a pleurodesis (fusion of the visceraland parietal pleura). This can be done by instilling a sclerosing agent Presented in part at the American College of Chest through a chest tube or via talc insufflation at thoracoscopy.1 These Physicians Annual Meeting, New Orleans, Louisi-ana, October 1997.
treatments require the insertion of a chest tube and several days ofhospitalization.
Supported by Denver Biomaterials, Denver, Colorado.
An alternative treatment is intermittent or continuous drainage of Drs. Richard Light, R. Michael Rodriguez, and Jo- the pleural fluid with a chronic indwelling pleural catheter. There seph Putnam own shares of stock in Surgimedics,which is a parent company of Denver Biomaterials.
have been several other reports with small numbers of patients thatdemonstrated the utility of an indwelling drainage catheter in pa- Address for reprints: Richard W. Light, M.D., Directorof Pulmonary Disease Program, Saint Thomas Hos- tients with MPE.2–7 Based on these preliminary reports, a pleural pital, P.O. Box 380, 4220 Harding Road, Nashville, TN catheter was developed that could be chronically implanted in the pleural space for the treatment of MPE.
Received June 7, 1999; accepted July 2, 1999.
The purpose of this randomized study was to compare the effec- Indwelling Catheter for Malignant Effusions/Putnam et al.
FIGURE 1. The Pleurx indwelling pleural catheter is shown. The valve on the distal end of the pleural catheter is closed except when the access tip of the drainage
tiveness of the indwelling pleural catheter with tube films, 3) blunting of the costophrenic angles, 4) mod- thoracostomy and doxycycline pleurodesis in the erate effusion fluid between the costophrenic angle management of patients with recurrent, symptomatic and hilar level, 5) large effusion fluid above hilar level MPE. We hypothesized that use of the newly devel- but not completely opacified, and 6) complete opaci- oped pleural catheter compared with doxycycline pleurodesis would decrease hospital stay and result ina comparable improvement in quality of life without Patient Selection
Patients were required to have a malignancy with atleast a moderate sized pleural effusion and dyspnea MATERIALS AND METHODS
relieved after therapeutic thoracentesis. Exclusion cri- A prospective, randomized, multicenter study was teria included chylothorax, previous lobectomy or conducted comparing the treatment of symptomatic, pneumonectomy on the affected side, previous at- recurrent MPE with an indwelling pleural silicone tempts at pleurodesis, autoimmunodeficiency syn- catheter (Pleurx; Surgimedics, Denver Biomaterials, drome, Karnofsky performance status score Ͻ 50,8 Denver, CO) to doxycycline pleurodesis via tube tho- bilateral moderate or larger pleural effusions, multiple loculations, mediastinal shift toward the side of theeffusion, pleural infection, or abnormal coagulation Description of Indwelling Pleural Catheter Apparatus
profile. Study participants were not allowed to receive The apparatus for the indwelling pleural catheter con- concurrent intrapleural chemotherapy or radiation sists of the catheter and a drainage line with an access therapy to the ipsilateral chest. Patients were allowed tip matched to the catheter (Fig. 1). The pleural cath- to receive systemic chemotherapy or mediastinal ra- eter is a 15.5 Fr. silicone rubber catheter, 66 cm in length, with fenestrations along the proximal 24 cm.
On the distal end is a valve designed to enhance thesafety of the product. The valve prevents fluid or air Study Design
from passing in either direction through the catheter After a written informed consent was obtained, pa- unless the catheter is accessed with the matched tients were randomized via consecutively numbered drainage line. The pleural fluid is drained by inserting envelopes to receive the indwelling catheter or the the access tip of the drainage line into the valve of the doxycycline pleurodesis. A 2:1 distribution was used catheter and then draining the fluid via an external with the greater number of patients receiving the in- dwelling catheter. Each center was provided a set ofconsecutively numbered envelopes containing the Radiologic Evaluation
treatment assignment that was generated from a table Pleural effusions were semiquantitated as follows: 1) no effusion, 2) effusions only detected on decubitus The patient’s disability was assessed by using the CANCER November 15, 1999 / Volume 86 / Number 10
modified Borg scale score for dyspnea (scale, 0 –10) at patient assessed the most severe and average levels of rest and after walking 100 feet on the level.9 A quality- pain during the previous 24 hours using a visual ana- of-life questionnaire, the dyspnea component of Guyatt Chronic Respiratory Questionnaire (CRQ), also The chest tube was removed when the 24-hour drainage fell below 100 mL. If the 24-hour drainagevolume did not fall below 100 mL within 4 days, then Protocol for Catheter Patients
doxycycline was readministered. If the drainage re- The Seldinger technique11 was used to insert the wire mained above 100 mL/24 hours for 4 days after the into the pleural effusion at approximately the anterior second injection, then the patient was considered to axillary line. A 1–2 cm incision was made over the wire.
have experienced treatment failure. All patients who A chest wall tunnel (5– 8 cm in length) was created were thought to be initial treatment successes had with a counter incision. The catheter was pulled chest radiographs within 8 hours of chest tube re- through the tunnel and out next to the wire. After moval and had their dyspnea reassessed.
dilation of the wire tract with a Teflon “peel-away”sheath, the indwelling catheter was inserted into thechest. The counter incision was closed primarily, and Follow-Up Procedures
the catheter was secured to the skin medially with a Follow-up clinic visits were scheduled at 4 weeks, 8 weeks, and 12 weeks. For the first 12 weeks, patients After catheter insertion, up to 1500 mL of pleural were called on a weekly interval if a clinic visit was not fluid initially were drained. If the effusion was not scheduled. After the initial 12 weeks, patients were drained completely, as evaluated with the chest radio- called on every other week. Chest radiographs, interval graphs, then another 1000 mL of fluid were drained history, and physical examination were obtained at every 8 hours until drainage was complete. If the pa- each clinic visit. The patient’s dyspnea was quanti- tient was found to have a trapped lung, then the tated with a Borg score, and their quality of life was catheter was left in place. The patient was considered assessed by the Guyatt CRQ. Pleural catheter patients for discharge after a chest radiograph demonstrated were followed until either death or catheter removal.
the absence of fluid. Prior to discharge, the patient’s Pleural catheter patients were advised to return for a dyspnea was rerated using the Borg scale. The patient follow-up visit sooner if there was no pleural fluid assessed the most severe and average levels of discom- drainage on 3 consecutive occasions. If pleurodesis fort during the 24 hours after catheter insertion using had occurred, then the catheter was removed. After discharge, the patients were said to have failed treat- Prior to discharge, the patients and/or their care ment if the effusion was large (Grade 5) or if the givers were provided with detailed oral and writteninstruction for draining the pleural fluid. Patients were effusion was moderate (Grade 4) and the patient was instructed to drain the pleural fluid completely every Protocol for Doxycycline Pleurodesis Patients
Statistical Analysis
After tube thoracostomy (chest tube size was at the The data are presented as the mean Ϯ standard devi- discretion of the investigator) was performed, the ation when the data are distributed normally and as pleural fluid was drained. If the underlying lung failed the median with the range when the data are not to expand by 72 hours, then the patient was assumed distributed normally. The characteristics of the pa- to have a trapped lung, and chemical pleurodesis was tients in the two groups (pleural catheter or doxycy- not attempted. If the lung expanded and the drainage cline pleurodesis) were compared by using unpaired t was Ͻ150 mL/24 hours, then doxycycline (500 mg in a tests. If the data failed the normality test, then the total volume of 50 mL) was injected into the pleural results were compared by using the nonparametric space. If the chest tube had been in place for 4 days Mann–Whitney rank-sum test (SigmaStat; Jandel Sci- and the drainage was Ͻ300 mL over the previous 24 entific, San Rafael, CA). The chi-square test was used hours, then doxycycline was injected. If the drainage for statistical analysis when proportions in the treat- exceeded 300 mL during Day 4, then chemical pleu- ment groups were compared. Differences in the treat- ment results were considered significant when P Ͻ After doxycycline injection, the chest tube was 0.05. When the treatment results were analyzed, only clamped for 4 hours, and the patient was rotated.
the patients who received the appropriate treatment Suction was then reapplied. The following day, the without protocol violation were included.
Indwelling Catheter for Malignant Effusions/Putnam et al.
Comparison of Demographics of the Patients in the Two Treatment
Treatment Results from the Two Treatment Groups
Pleural catheter
a P Ͻ 0.001 compared with pleural catheter group.
justified in the protocol. The initial treatment was unsuccessful in 13 of the remaining 41 patients (32%) for the following reasons: Ͼ300 mL of fluid/24 hours after 4 days of tube drainage (n ϭ 7 patients), incom- plete drainage (n ϭ 3 patients), trapped lung (n ϭ 1 patient), recurrent large effusion immediately afterchest tube removal (n ϭ 1 patient), and death 3 daysafter chest tube insertion (n ϭ 1 patient). The median chest tube size was 28 Fr (range, 14 –36 Fr).
One hundred forty-four patients were enrolled in thestudy at 11 institutions. Forty-five patients (31.2%) Indwelling Pleural Catheter Patients
were randomized to the doxycycline arm, and 99 pa- Three of the 99 patients who were randomized to the tients (68.8%) were randomized to the indwelling indwelling catheter group did not have the catheter inserted. In 2 patients, the radiographs were misinter- The demographics of the patients assigned to the preted. The third patient had a loculated effusion. Two two treatment groups were similar (Table 1). The most of 96 patients who received the indwelling catheter common primary malignancy in each group was lung, were withdrawn because of protocol violations: One and the second most common was breast (Table 1).
patient had a concomitant chest tube, and the other The mean initial size of the effusions in the indwelling had a chylothorax. In the remaining 94 patients, the catheter group was significantly larger (P ϭ 0.031) chest radiograph revealed at most a small effusion in than in the doxycycline pleurodesis group. The mean 91 patients (97%). A multiloculated effusion, a hemo- pleural fluid glucose and LDH levels and the percent- thorax, and a pleural infection each occurred in 1 age with positive cytology were similar in both groups.
Doxycycline Pleurodesis Patients
Hospitalization Times
Two of the 45 patients who were randomized to the The median hospitalization time necessary for the doxycycline pleurodesis group did not receive chest treatment of pleural effusions was significantly less in tubes. One patient was withdrawn from the study the pleural catheter group (median, 1.0 day) than in when his primary care physician elected to treat with the doxycycline pleurodesis group (median, 6.5 days; radiotherapy rather than a chest tube. A second pa- P Ͻ 0.001) (Table 2). This time was the interval from tient withdrew from the study after he learned that he randomization until the patients were eligible for dis- was randomized to receive a chest tube rather than an charge based on their response to treatment and its indwelling catheter. Of the remaining 43 patients, 2 complications. The study was designed to have all were withdrawn due to protocol violations. One pa- indwelling catheter patients discharged after being tient was mistakenly given talc rather than doxycy- observed for 16 –24 hours in the hospital after inser- cline intrapleurally, whereas a second patient received tion of the catheter. Forty of the indwelling catheter a second administration of doxycycline before it was patients were discharged within 24 hours. Hospitaliza- CANCER November 15, 1999 / Volume 86 / Number 10
Comparison of Initial Borg and Guyatt Scores and Mean Improvements from the Initial Score in the Two Treatment Groupsa

Borg score rest
Borg score exercise
Guyatt CRQ
Time group
CRQ: Chronic Respiratory Questionnaire.
a The numbers in parentheses refer to the number of patients evaluated at each time period. All numbers are the mean Ϯ standard deviation of differences from initial values.
b P ϭ 0.050.
tions were prolonged in the other patients for therapy mented recurrence at another medical center, and it was not clear whether the catheter was occluded.
Spontaneous Pleurodesis
Spontaneous pleurodesis occurred in 42 of the 91 pa-
Changes in Quality of Life
tients (46%) who were treated successfully with the The initial mean values for the resting and exercise pleural catheter. The median time to pleurodesis was Borg score and the dyspnea component of the Guyatt 29 days (range, 8 –223 days). The median amount of CRQ were similar among the two groups (Table 3).
fluid drained in the first week as an outpatient was When the Borg scores were re-evaluated after the ini- significantly less in the group that achieved pleurode- tial treatment was completed, the mean degree of sis than in the group that did not (460 mL vs. 1275 mL; improvement both at rest and after exercise were P Ͻ 0.05). Overall, the median amount of fluid drained nearly identical among the two treatment groups. The each week ranged from 500 mL to 1500 mL, with the Borg scores postexercise at 30 days, 60 days, and 90 maximum Ͻ 4000 mL/week. Patients who achieved a days after the initial treatment showed a trend toward pleurodesis tended to have a gradual diminution in greater improvement in the indwelling catheter group, which was statistically significant at 30 days (P ϭ 0.05)(Table 3). The improvements in the Guyatt CRQ scores Late Failures
were similar 30 days, 60 days, and 90 days posttreat- In the doxycycline group, late failure was defined as recurrence of the effusion after an initially successfulpleurodesis, whereas, in the pleural catheter group,late failure was defined as the recurrence of the effu- Concomitant Therapy
sion after its initial successful control. The late failure At the time that the patients were enrolled in the rate was comparable in the doxycycline group (6 of 28 study, 25 of the 135 evaluable patients were receiving patients; 21%) and in the indwelling catheter group chemotherapy. There was no significant relation be- (12 of 91 patients; 13%) (chi-square ϭ 0.23; P ϭ 0.631).
tween the results from the doxycycline group or the The 6 late failures in the doxycycline group were all indwelling catheter group and whether or not the pa- documented by X-ray and by thoracentesis in four. All tients were receiving chemotherapy (Table 4). At 30 6 recurrences occurred by 30 days. In the indwelling days postrandomization, an additional 3 patients in catheter group, the recurrence was due to loculations the doxycycline group and 13 patients in the indwell- resulting in incomplete drainage of the pleural space ing catheter group were receiving chemotherapy.
in 7 patients. The catheter was repositioned in 1 of Again, there was no relation between chemotherapy these patients, who subsequently developed a spon- and the results from the doxycycline group or the taneous pleurodesis. The recurrence occurred after a indwelling catheter group. There was no relation be- successful, spontaneous pleurodesis in 2 patients. In 2 tween the occurrence of a spontaneous pleurodesis patients, the catheter became occluded. It was re- and chemotherapy in the indwelling catheter group.
placed in 1 patient who subsequently developed a Only 1 patient in the entire group received radiother- spontaneous pleurodesis. One patient had a docu- apy to the mediastinum or chest wall.
Indwelling Catheter for Malignant Effusions/Putnam et al.
Relation between Chemotherapy at the Time of Initial Treatment and
The current study demonstrates that patients with Results of Treatment
symptomatic, recurrent MPEs can be managed effec- Doxycycline
tively with a chronic indwelling pleural catheter. The pleurodesis
primary advantage of this method is decreased hospi- chemotherapy
talization time compared with that necessary forchemical pleurodesis via tube thoracostomy. There were more complications during follow-up in the pleural catheter group, but these complications Because the life expectancy of patients with MPEs is short, efforts should be made to minimize the du-ration of their hospitalization. The median survival of90 days in the current study is similar to that reported Morbidity
in previous studies.12,13 Therefore, a reduction in the The degree of pain experienced in the two groups was median hospitalization time from 6.5 days to 1.0 day, similar. The maximum and average degree of pain which occurred in the current study with the indwell- experienced in the first 24 hours after the procedure ing catheter group, increases the time that the patients were 55.5 Ϯ 37.6 and 28.1 Ϯ 28.6, respectively, in the doxycycline pleurodesis group and 44.3 Ϯ 29.2 and One possible criticism of the current study is the 23.7 Ϯ 20.2, respectively, in the pleural catheter group.
manner in which the efficacy of the two procedures Almost all patients received opiates for analgesia dur- was compared. Our primary measure of efficacy was ing the first day, and there was no significant differ- the percentage of patients who had a late recurrence ence in the amount of analgesic received.
of the effusion and an initially successful procedure.
Early (in-hospital) morbidity occurred in 6 of 43 The incidence rate of late recurrence was 6 of 28 patients who received a chest tube: fever (n ϭ 2 pa- patients (21%) in the doxycycline group and 12 of 91 tients), severe pain requiring PCA (n ϭ 2 patients), patients (13%) in the indwelling catheter group. There hydropneumothorax (n ϭ 1 patient), and occluded are two different measures that can be used. The first chest tube requiring tube replacement (n ϭ 1). Early is the initial success rate, which compares the percent- (in-hospital) morbidity occurred in 10 of 96 patients age of initially successful pleurodesis in the doxycy- with the indwelling catheter: fever (n ϭ 3 patients), cline group with the percentage of initially complete pneumothorax (n ϭ 3 patients), misplacement of drainages in the indwelling catheter group. By using catheter (n ϭ 2 patients), re-expansion pulmonary this comparison, the indwelling catheter appears su- edema (n ϭ 1 patient), and hypercapnic respiratory perior, because, with this measure, the treatment was failure secondary to over-sedation (n ϭ 1 patient). No successful in 91 of 94 patients (97%) in the indwelling catheter group but in only 28 of 41 patients (68%) in In the 90-day follow-up period, there were several the doxycycline pleurodesis group. We chose not to complications in the pleural catheter group. Three use this analysis, because the design of the study ob- patients developed tumor seeding of the catheter tract viously was biased in favor of the indwelling catheter that did not require therapy. Six patients developed group. Patients in the doxycycline group who had a local cellulitis around the catheter tract that re- trapped lung or large amounts of fluid after the chest sponded to oral antibiotics and did not necessitate tube was placed would be considered to have experi- catheter removal. Pain during fluid drainage was re- enced failure in the doxycycline group but not in the ported by an additional 7 patients. The only compli- cation reported in the doxycycline pleurodesis group The second measure by which the two procedures was pain at the chest tube site in 1 individual.
can be compared is long term control of the effusionwithout the presence of the catheter. By using this Survival
comparison, doxycycline pleurodesis appears supe- The median survival was poor but similar for both rior, because it was effective in 22 of 41 patients (54%), groups. For the chest tube patients (n ϭ 35 patients), whereas the indwelling catheter was effective in only the median survival was 90 days, whereas, for the 30 of 91 patients (33%). This analysis is biased against pleural catheter group (n ϭ 87 patients), the median the indwelling catheter group, because a pleurodesis would have to occur for the treatment to be classified CANCER November 15, 1999 / Volume 86 / Number 10
as successful. We maintain that a treatment is success- the indwelling catheter also had to drain their pleural ful as long as there is no pleural fluid, whether or not fluid at home until they developed a spontaneous pleurodesis. After the patients and/or their care givers There are several methodological weaknesses to were provided detailed oral and written instruction for the current study. First, the study was not blinded for draining the pleural fluid, most patients had no diffi- obvious reasons. Accordingly, the investigators could culty in following the protocol. Although the study have been biased in assessing patient symptoms, ra- coordinators were available at all times for questions, diographs, or capability of being discharged. Second, they rarely were contacted except when the catheter the study was designed so that pleural catheter pa- tients could be discharged within 16 –24 hours, It is noteworthy that spontaneous pleurodesis oc- whereas the doxycycline pleurodesis patients had to curred in nearly 50% of the patients treated with the remain in the hospital for a minimum of 3 days. If the indwelling pleural catheter by unknown mechanisms.
sclerosing agent had been injected as soon as the lung When patients are treated with tube thoracostomy for re-expanded, and if the chest tube had been removed several days, pleurodesis will develop in a significant 24 hours after the injection of the sclerosing agent, as proportion of patients.20,21 In contrast, it is very uncom- proposed previously,14 then there may have been less mon for patients who are treated with serial therapeutic of a difference in days of hospitalization. However, thoracenteses to develop a spontaneous pleurodesis.22 other studies have shown that the median duration of We believe that two conditions are necessary to induce a hospitalization for pleurodesis with tube thoracos- spontaneous pleurodesis, namely, the pleural space must be completely drained, and there must be inflam- The results of the current study for doxycycline mation in the pleural space. Placement of a chest tube pleurodesis tend to be slightly worse than those re- ported previously with tetracycline pleurodesis. In a When a patient is seen with a symptomatic recur- review of pleurodesis for MPEs, treatment was suc- rent pleural effusion, available treatment options in- cessful in Ϸ70% of patients who were treated with clude serial thoracentesis, thoracoscopy with chemi- intrapleural tetracycline derivatives,18 whereas, in the cal pleurodesis, tube thoracostomy with chemical current study, the treatment was successful in only pleurodesis, insertion of a pleuroperitoneal shunt, or 54% of patients. However, in another study, treatment insertion of an indwelling pleural catheter. Factors was successful in only 33% of patients at 30 days.13 At that should be considered when making this choice the present time, talc slurry is one of the most popular include cost, hospitalization time, symptom relief, sclerosing agents, and it may be more effective than convenience, patient acceptance, complications, and the tetracycline derivatives.18 However, acute respira- tory failure has resulted from its administration,19 andthe duration of hospitalization required is comparable We believe that the indwelling pleural catheter is a to that for patients who are receiving tetracycline de- good option for most patients with MPE primarily rivatives.15–19 Doxycycline rather than talc slurry was because of the reduced hospitalization time and the chosen for the current study because of the concern potential for outpatient use. In this study, a hospital- about the acute respiratory distress syndrome with ization of less than 1 day was required for the majority talc slurry and the limited availability of sterile talc at of patients treated with the indwelling catheter. In contrast, median hospitalizations exceeding 5 days are The indwelling pleural catheter required less hos- reported commonly for patients who received pleu- pitalization time; however, what were the drawbacks rodesis with either tube thoracostomy15–17 or thora- to its use? Table 2 shows that 12 of the 91 patients coscopy.15 The initial success rate with the indwelling (13%) with the indwelling catheter experienced a com- catheter exceeds 90%, and only Ϸ10% of the catheters plication after discharge from the hospital compared fail when they have been successful initially. Patient with no complications in the doxycycline pleurodesis acceptance is good, symptoms are relieved, and com- patients. However, the patients with cellulitis were plications, for the most part, are minor. The major treated successfully with oral antibiotics, and the pa- disadvantage of the indwelling catheter is the neces- tients with tumor seeding of the catheter tract did not sity for the repeated drainage of the pleural space at require treatment. Only the patient with the pleural home should spontaneous pleurodesis not occur.
infection required hospitalization. These additional Additional research is indicated to determine complications in the indwelling catheter patients whether the injection of sclerosing agents through the seem minor compared with the extended hospital stay indwelling catheter can be performed safely on an associated with doxycycline pleurodesis. Patients with outpatient basis. Indwelling catheters have been used Indwelling Catheter for Malignant Effusions/Putnam et al.
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VOLUNTARY SECTOR Introduction Voluntarism is an integral part of Indian society and dates back to ancient times when it operated in the fields of education, medicine, cultural promotion, and in crises such as droughts and famines. Modern indigenous forms of voluntary organisations began to appear in the colonial period. According to the World Development Report (World Bank, 1993),"

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The Journal of International Medical Research 2004; 32: 132 – 140 Z ZAKAY-RONES1, E THOM2, T WOLLAN3 AND J WADSTEIN41Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel;2PAREXEL Norway AS, PO Box 210, N-2001 Lillestrøm, Norway; 3Jernbanealléen 30, N-3210Sandefjord, Norway; 4Østra Rønneholmsv 6B, 21147 Malmö, Sweden Elderberry has been used in folk

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