תוצאת חיפוש

Information Provided for Informed Consent in Clinical Trials

Avishay Sella

Genitourinary Medical Oncology Unit, Dept. of Oncology, Rabin Medical Center (Beilinson Campus), Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University

The Helsinki Declaration contains recommendations guiding physicians who conduct clinical trials. One is that the requirement for informed consent is essential for approval of a trial. An important component of the informed consent doctrine is that all data required for the participant's decision must be provided. We analyze data of a therapeutic trial, and define 12 data components outlined in, or directly derived from the Helsinki Declaration.

61 instances of informed consent for therapeutic clinical trials from various fields of medicine, from 1994 to 1997, were analyzed. In each the presence of the 12 components was evaluated.

The data demonstrated that there were only 5 components cited in most cases of informed consent: trial objectives, methods, treatment plan, risks, and the option of withdrawing. Benefit to the participant was mentioned in half the cases, while only limited information was provided about other components such as life-threatening and unpredictable risks, and alternative treatment.

Examples of informed consent from 1997 showed statistical improvement since 1994 in the data concerning trial objectives, methods, risks and alternative therapy. Informed consent documents of international multicenter trials compared with local trials showed statistical improvement in the data components of the trial objectives, methods, and risks, including those of potentially life-threatening and unpredictable risks, and alternative therapy. Analysis of informed consent showed that not all components required for a comprehensive decision regarding participation in a clinical trial are included. These data emphasize the need to design a structured informed consent protocol in which all the required data components are specifically outlined for potential participants.

1000 Cardiac Catheterizations in Congenital Heart Disease

Benjamin Zeevi, Galit Bar-Mor, Michael Berant

Cardiac Catheterization Unit, Schneider Children's Medical Center, and Sackler School of Medicine, Tel Aviv University

Over the past 15 years, percutaneous therapeutic cardiac catheterization has become increasingly important in the treatment of congenital heart disease. We describe our experience in 1000 such catheterizations between 1993-1997. 55% were in 1-12-year-olds; only 20% were in patients younger than 1 year old and 11.3% were in adults with congenital heart defects. In about 50% it was at least a second cardiac catheterization. Overall, there were 425 therapeutic cardiac catheterizations, increasing from 33% in the first 200 procedures, to 63% in the last 200.

We performed 30 different types of therapeutic catheterizations: 23.3% were valvular dilations, 21.4% vessel angioplasties, 36.9% closure procedures, 9.2% electrophysiological procedures, and 9.2% miscellaneous. In 31.3% of therapeutic catheterizations we used 12 new procedures. Minor complications occurred in 8.5% and major in 0.6%; most complications were successfully treated or were self-limited and there was no residual damage.

In this report the current role of each type of major catheterization is discussed on the basis of our experience. Further development of technology for lesions not amenable to currently available transcatheter methods, and longer follow-up for current techniques will consolidate the role of therapeutic cardiac catheterization in congenital heart disease.

Laparoscopy for Common Bile Duct Stones

Ibrahim Matter, Moshe Wald, Shmuel Eldar

Depts. of Surgery and Urology, B'nai-Zion Medical Center, Haifa

We performed 75 laparoscopic cholecystectomies during July and September 1996. In 3 men and 4 women, aged 32-87 years, there was obstructive jaundice caused by choledocholithiasis. During laparoscopy in the jaundiced patients, calculi were identified by cholangioscopy and intra-operative cholangiography. They were washed into the duodenum (confirmed cholangiographically) after intravenous glucagon injections and dilation of the papilla of Vater.

Serum bilirubin and liver enzyme levels returned to normal within a few days. There was no operative or postoperative morbidity, nor any biliary-related systemic complications. Average postoperative hospitalization was 3 days.

Balloon Angioplasty of Native Coarctation of the Aorta

Benjamin Zeevi, Galit Bar-Mor, Michael Berant

Cardiac Catheterization Unit, Schneider Children's Medical Center, Petah Tikva, and Sackler School of Medicine, Tel Aviv University

The use of balloon dilatation to treat native coarctation of the aorta is gaining acceptance among interventional pediatric cardiologists, but is still controversial. We describe our experience with this procedure in 21 children, mean age 5.6 years and mean weight 21.1 kg. Most had an additional congenital heart defect, most commonly a bicuspid aortic valve. 17 were asymptomatic, 3 had tachypnea and 1 infant had severe congestive heart failure and was ventilated. The mean systolic blood pressure was 129.7 mm Hg.

Balloon dilatation was successful in 90% (19), decreasing the mean maximal systolic gradient from 35.3 to 9 mm Hg (p<0.001), and increasing the narrowest area from 3.9 to 8.2 mm (p<0.001), with a mean balloon-to-coarctation width-ratio of 2.8. There were no complications. Of 15 who underwent repeat cardiac catheterization at a mean interval of 10.6 months, 2 had a maximal systolic gradient of more than 20 mm Hg. 1 of these underwent successful repeat angioplasty and the other, who also had a small aneurysm, underwent surgical repair successfully. 2 others had small aneurysms and they are being followed clinically.

All patients were seen again after a mean interval of 31 months. The mean systolic blood pressure was 104 mm Hg, significantly lower than before intervention (p<0.002). 1 had an increased pressure gradient between right arm and leg of 35 mm Hg at later follow-up, and repeat cardiac catheterization demonstrated a good result 13 months after the initial procedure. She is awaiting a third catheterization. Overall, 90% had good mid-term results.

Based on our experience and recent reports, balloon angioplasty is safe and effective in most children older than 7 months and should be considered a viable alternative to operation for discrete aortic coarctation. Further long-term evaluation is needed.

Exhaustion of Motor Cortex after Head Injury Revealed by Trans-Cranial Magnetic Stimulation

M. Elron, G. Levi, M. Trovnick, J.F. Soustiel, H. Hafner, A. Chistyakov, M. Feinsod

Center for Treatment and Applied Research in Head Injury, Dept. of Neurosurgery, Rambam Medical Center and Rappaport Faculty of Medicine, The Technion, Haifa

We evaluated the pattern of motor evoked potentials elicited by single-pulse and slow-rate (1 Hz) repetitive, transcranial, magnetic stimulation (RTMS) in minor head injuries. The motor response to a single magnetic stimulus in patients with minor head injury was characterized by a significantly higher threshold than in healthy subjects. However, central and peripheral motor conduction was normal in all patients. A stable pattern of MEP throughout the RTMS session was the most prominent feature in the control group. A progressive decrease in MEP amplitude and irregular alternation of large and very small MEPs over the course of RTMS was observed in minor head injury. The higher threshold of the motor response and the abnormal patterns of MEP behavior revealed by RTMS may reflect impaired excitability and enhanced exhaustion of the motor cortex in patients with minor head injuries, which improve with time.

D-Lactic Acidosis in Short Bowel Syndrome

Ben-Ami Sela, Joseph Zlotnik, Tamar Masos, Joseph Danieli, Sarah Mazia-Beni, Anita Jonas

Institute of Chemical Pathology and Pediatric Intensive Care and Gastroenterology Units, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University

A boy of 20 months and a girl of 27 months who had previously undergone massive bowel resection due to congenital intestinal obstruction are described. During grad-ual reduction of total parenteral nutrition and initiation of oral feeding, both developed severe, acute metabolic acidosis, accompanied by encephalopathy and ataxia. After the laboratory identification of massive amounts of the d-Disomer of lactic acid in urine and blood, both were successfully treated with IV bicarbonate, and metronidazole to suppress the overgrowth of colonic lactobacilli responsible for the metabolic crisis.

Muir-Torre Syndrome: Importance of Clinical Diagnosis and Genetic Investigation

Hana Strul, Paul Rozen, Tova Naiman, Ruth Shomrat

Gastroenterology Dept. and Genetics Institute, Tel Aviv Medical Center and Tel Aviv University

Muir-Torre syndrome is a relatively rare cutaneous manifestation of hereditary nonpolypous colorectal cancer (HNPCC). This autosomal dominant syndrome is characterized by a combination of sebaceous gland and malignant visceral tumors. The common sites of internal malignancies are the gastrointestinal tract and urinary system. It appears in early adult life and its clinical course is relatively slow.

In some families genetic diagnosis can identify asymptomatic carriers of the mutation. All first-degree relatives, especially mutation carriers, should be referred from the age of 20 years for routine follow-up and early treatment, as it has been proven to decrease morbidity and mortality.

We present a 51-year-old man with Muir-Torre syndrome diagnosed by the presence of multiple adenomas of sebaceous glands, colonic adenoma and adenocarcinoma of the duodenum. The family history was typical for HNPCC. A mutation in the hMSH2 gene on chromosome 2p was found in the patient and in several asymptomatic family members. The aim of this report is to increase awareness of this syndrome and emphasize the importance of referring patients and their families for clinical and genetic counseling and diagnosis.

Combination Chemotherapy in Metastatic Urothelial Cancer

A. Sella, D. Flex, D. Gafni, O. Rabinovitz, A. Sulkes, J. Baniel

Genitourinary Medical Oncology Unit, Depts. of Oncology and Urology, Rabin Medical Center, Beilinson Campus, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv

The treatment of metastatic urothelial cancer is based on the combination of cisplatin, methotrexate, vinblastine and adriamycin (M-VAC). From November 1994 to May 1997 we treated 25 patients (51 men, 3 women, aged 50-77) with M-VAC. The tumor originated from the urinary bladder in 14 (56%) and the upper urinary tract in 11 (44%). Disease sites included: primary - 5 (25%), lymph nodes - 17 (68%), lungs - 10 (40%), bones - 8 (32%), pelvic mass and liver each - 4 (16%), with an overall median of 2 (1-5) sites per patient.

9 patients (38%) had complete responses and 8 (32%) had partial responses, for an overall response rate of 68% (95% CI 48.5%-85%). The median duration of response was 15.3 (1.6-29.6+) months. Median survival of responders was 19.1 (4.8-35.7+) months compared to 6.2 (0.7-11.2) for the non-responders (p<0.05). 13 (52%) of patients are alive, of whom 8 (32%) are free of disease and 5 with a single metastatic site on presentation at follow-up.

In the 118 treatment cycles we observed grade III-IV toxicity: myelosuppression 53 (45%), thrombocytopenia 4 (3%), stomatitis 8 (6.7%), diarrhea 3 (2.5%). There were 22 infectious episodes and 1 patient died of sepsis.

We achieved a high response rate with the combination M-VAC. However, only a third had long-term disease-free states and treatment was associated with excessive toxicity. Thera-peutic approaches with new agents are required to improve the response rate and toxicity.

Percutaneous Closure of Patent Arterial Ducts with Occluding Spring Coils

Benjamin Zeevi, Galit Bar-Mor, Michael Berant

Cardiac Catheterization Unit, Schneider Children's Medical Center, Petah Tikva and Sackler School of Medicine, Tel Aviv University

In recent years percutaneous closure of small and medium- sized patent arterial ducts has been achieved using occluding spring coils. We describe our experience in 93 patients with this tec, using a snare to facilitate the procedure in most. All patients had a clinically apparenpatent arterial duct and had undergone attempts at transcatheter closure at a mean age of 6.8 years. In 1, the duct was a residual lesion following surgical ligation, and in 5 it was a residual following attempted closure with the Rashkind double-umbrella. The mean narrowest diameter of the ducts was 2.1 mm.

In our 93 patients implantation was successful in 92 (99%), using 1 coil (82 patients), or 2 (10 patients), and in 1 by a combination of a double-umbrella device and an occluding spring coil.

The mean fluoroscopic screening time for the whole group was 22.8 minutes, which decreased to 16.8 minutes in the last 50 patients. The coil embolized in 7 patients, but was retrieved in 6 and the ducts were subsequently occluded with another coil. In 1 patient the coil was left in a distal small branch of the left pulmonary artery and the duct was successfully occluded with a double-umbrella.

Color-Doppler echocardiogram performed the morning after placement of the coils showed residual leaks in 18%. At mean follow-up of 24.6 months repeat imaging showed residual leaks in only 3 of these patients (3%).

We conclude that occlusion of small to medium-sized ducts using coils appears to be effective and is the treatment of choice. The use of a snare to hold and manipulate the coil as it is delivered improves control of the coil, the accuracy of its placement, as well as giving complete occlusion of the ducts.

Ambulatory Oral Procedures on Low-Dose Aspirin

Ronen Gaspar, Leon Ardekian, Benyamin Brenner, Micha Peled, Dov Laufer

Dept. of Oral and Maxillofacial Surgery, and Thrombosis and Hemostasis Unit, Rambam Medical Center, Haifa

Discontinuation of long-term, low-dose aspirin prior to ambulatory oral surgical procedures was assessed in a blind, controlled prospective study. 50 patients on low-dose aspirin who needed dental extractions, periodontal surgery, or other ambulatory oral surgery were randomly divided into test and control groups. The control patients stopped taking aspirin a week before operation, but in the test group aspirin was continued. Before, during and after surgery bleeding time was tested. Although bleeding time was significantly longer when aspirin was continued, in both groups it was within normal limits. Intraoperative hemorrhage was more frequent in those taking aspirin. Hemostasis control posed no problem and there were no postoperative complications in either group. It is concluded that discontinuing low-dose aspirin prior to elective oral surgery is not justified.

The Fate of Gallstones "Dropped" during Laparoscopy

Menashe Barzilai, Arie Bitterman, Dorit Schlag-Eisenberg, Nathan Peled

Depts. of Radiology and Surgery B, Carmel Medical Center, Haifa

Laparoscopic cholecystectomy is considered the procedure of choice for removing symptomatic, stone-containing gallbladders. It is estimated that in 30-40% of these operations stone(s) spill into the peritoneal cavity. It was assumed that these "dropped stones" are harmless and are dissolved and absorbed spontaneously. We present a 70-year-old woman in whom such a stone, dropped during laparoscopy, led to formation of an intraperitoneal abscess.

Comparison between Every-Day and Every-3-Days Fluoxetine in Young, Moderately Depressed Out-Patients

A. Shiber, H. Reuveni, A. Elhayany, I.Z. Ben-Zion

Psychiatric Dept., Psychiatric Division, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba; and Medical Division for Drug Utilization, Kupat Holim Klalit (Sick Fund)

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half- life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day.

To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months.

Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Radiologic Appearance of "Falling Gallstones" during Laparoscopic Cholecystectomy

E. Alkalay, D. Yaffe, Z. Spindel

Eyn Vered Clinic and Depts. of Radiology and Surgery, Sapir Medical Center, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University

Laparoscopic cholecystectomy is the "gold standard" in treating cholelithiasis. Stones are frequently lost in the peritoneal cavity during the procedure, but "missing stones" have been regarded as insignificant. However, there is accumulating evidence that untreated "lost" stones may cause complications even years after operation.

We present a 65-year-old woman who presented with vague complaints, anemia and an elevated ESR. CT scan showed an infiltrating process in extra-abdominal muscles compatible with sarcoma. At operation, 2.5 years after previous laparoscopic cholecystectomy, an abscess was found which contained biliary stones. Because of their small size they were not visible on CT scan. We discuss the possible ways of handling "falling stones."

Autonomic Dysregulation in Post-Traumatic Stress Disorder: Power Spectral Analysis of Heart Rate Variability

Hagit Cohen, Uri Loewenthal, Mike A. Matar, Hanoch Miodownik, Zeev Kaplan, Yair Cassuto, Moshe Kotler

Mental Health Center, Israel Ministry of Health; Anxiety and Stress Research Unit, Faculty of Health Sciences; Dept. of Life-Sciences, Ben-Gurion University of the Negev, Beer Sheba

Spectral analysis of heart rate variability (HRV) has been shown to be a reliable noninvasive test for quantitative assessment of cardiovascular autonomic regulatory response, providing a dynamic map of sympathetic and parasympathetic interaction. In a prior study exploring the state of hyperarousal that characterizes the post traumatic stress disorder (PTSD) syndrome, we presented standardized heart rate analyses in 9 patients at rest, which demonstrated clear-cut evidence of a baseline autonomic hyperarousal state.

To examine the dynamics of this hyperarousal state, standardized heart rate analysis was carried out in 9 PTSD patients, compared to a matched control group of 9 normal volunteers. 20-minute ECG recordings in response to a trauma-related cue, as opposed to the resting state, were analyzed. The patients were asked to recount the presumed triggering traumatic event, and the control subjects recounted a significant stressful negative life event.

Whereas the control subjects demonstrated significant autonomic responses to the stressogenic stimulus of recounting major stressful experiences, the patients demonstrated almost no autonomic response to the recounting of the triggering stressful event. The patients demonstrated a degree of autonomic dysregulation at rest comparable to that seen in the control subjects' reaction to the stress model.

The lack of response to the stress model applied in the study appears to imply that PTSD patients experience so great a degree of autonomic hyperactivation at rest, that they are unable to marshal a further stress response to the recounting of the triggering trauma, as compared to control subjects. A subsequent study of the effect of medication on these parameters showed that they are normalized by use of selective serotonin re-uptake inhibitors (SSRI's).

Neither the clinical implications of these findings, nor their physiological mechanisms are clear at present. We presume that they reflect a central effect, as the peripheral automatic effects of SSRI's are relatively negligible.

Extensive Liver Resection: a Series of 72 Cases

Moshe Hashmonai, Doron Kopelman, Ahmed Assalia, Yoram Klein, Hani Bahus, Alex Beny, Yaakov Baruch

Depts. of Surgery B, Oncology and Unit for Liver Diseases, Rambam Medical Center and Technion Faculty of Medicine, Haifa

Partial liver resection is the treatment of choice for various liver diseases, including primary and secondary (metastatic) malignancies, benign tumors, cysts, abscesses, trauma, etc. Improved knowledge of hepatic anatomy and physiology, improved diagnostic techniques and more developed peri-operative treatment have reduced postoperative morbidity and mortality to acceptable levels.

We present a series of 72 liver resections, the majority of which were liver lobectomies or more extensive procedures performed during 1982-1997. The percentage of postoperative complications, which ranged from 1.3% to 19.4%, and mortality (8.3%; 6/72) are comparable to those of other large series in the world literature. We believe that better appreciation of the surgical potential of Israel by our medical community will improve our therapeutic approach to various liver diseases.