An audit of consent refusals in clinical research at a tertiary care center in India

Background and Rationale:

Ensuring research participants’ autonomy is one of the core ethical obligations of researchers. This fundamental principle confers on every participant the right to refuse to take part in clinical research, and the measure of the number of consent refusals could be an important metric to evaluate the quality of the informed consent process. This audit examined consent refusals among Indian participants in clinical studies done at our center.

Materials and Methods:

The number of consent refusals and their reasons in 10 studies done at our center over a 5-year period were assessed. The studies were classified by the authors according to the type of participant (healthy vs patients), type of sponsor (investigator-initiated vs pharmaceutical industry), type of study (observational vs interventional), level of risk [based on the Indian Council of Medical Research (ICMR) “Ethical Guidelines for Biomedical Research on Human Participants”], available knowledge of the intervention being studied, and each patient''s disease condition.

Results:

The overall consent refusal rate was 21%. This rate was higher among patient participants [23.8% vs. healthy people (14.9%); P = 0.002], in interventional studies [33.6% vs observational studies (7.5%); P < 0.0001], in pharmaceutical industry-sponsored studies [34.7% vs investigator-initiated studies (7.2%); P < 0.0001], and in studies with greater risk (P < 0.0001). The most common reasons for consent refusals were multiple blood collections (28%), inability to comply with the study protocol (20%), and the risks involved (20%).

Conclusion:

Our audit suggests the adequacy and reasonable quality of the informed consent process using consent refusals as a metric.KEY WORDS: Autonomy, consent, India, reason, refusal, risk     

Bacteremia in patients with cirrhosis of the liver.

Infections are frequent in patients with liver cirrhosis, as their defenses against infectious agents are altered. But bacteremia occurring in cirrhotic patients has seldom been reported in the literature. From 1981 to 1986, we collected 197 cases with 228 episodes of bacteremia for this retrospective study. The incidence of bacteremia in cirrhotic patients was 8.8%; no significant difference was noted between cirrhotic patients with variant etiologies of HBV(+), HBV(-) and alcohol. But the incidence increased with the severity of the disease (1%, 4.8%, 17.1% in Child's A, B, C groups, respectively). Gram-negative bacteria were the predominant microorganisms of bacteremia (75.6%). Among them, Escherichia coli, Klebsiella pneumoniae and Aeromonas hydrophilia were the three most commonly detected microorganisms. Gram-positive bacterias were detected in 21.2% of patients with bacteremia, with predominance of the Streptococcus group and Staphylococcus aureus. In about 26.3% of cases the infectious sources were the same by bacteria cultures as from blood. The most common sources were spontaneous bacterial peritonitis, urinary tract infection, pneumonia and biliary tree infection. In cirrhotic patients with and without bacteremia, the mortality rate increased significantly in the bacteremia group (54.8% vs 23.2%, P less than 0.05). By Child's classification, the mortality of patients with classes B and C increased significantly after onset of bacteremia. There was no significant difference in mortality between bacteremic patients in the HBV(+), HBV(-) and alcohol groups. In conclusion, bacteremia is a severe complication of liver cirrhosis and a sign of a poor prognosis.     

Rotary endodontics in primary teeth – A review

Endodontic treatment in primary teeth can be challenging and time consuming, especially during canal preparation, which is considered one of the most important steps in root canal therapy. The conventional instrumentation technique for primary teeth remains the “gold-standard” over hand instrumentation, which makes procedures much more time consuming and adversely affects both clinicians and patients. Recently nickel–titanium (Ni–Ti) rotary files have been developed for use in pediatric endodontics. Using rotary instruments for primary tooth pulpectomies is cost effective and results in fills that are consistently uniform and predictable. This article reviews the use of nickel–titanium rotary files as root canal instrumentation in primary teeth. The pulpectomy technique is described here according to different authors and the advantages and disadvantages of using rotary files are discussed.     

Non-O1 Vibrio cholerae Bacteremia in Patients with Cirrhosis: 5-yr Experience from a Single Medical Center

Objectives: To assess the clinical features and susceptibility of cirrhotic patients to non-01 Vibrio cholerae bacteremia and to provide our therapeutic experiences in this rare and highly lethal infection. Methods: Twenty-eight blood culture isolates of non-01 V. cholerae were identified by our clinical microbiology laboratory between July 1989 and June 1994. Patients with underlying cirrhosis and the aforementioned bacteremia were retrospectively reviewed. Results: Twenty-one cirrhotic patients (16 male, five female; mean age, 50.9 yr; range 28–67 yr) were identified and classified as Child B (6 cases) and Child C (15 cases). Bacteremic episodes occurred most often from March to September. Seafood ingestion (seven cases) and seawater exposure (two cases) were risk factors, but nosocomial infections were also noted in six cases. Presenting symptoms and signs included ascites (95.2%), fever (81%), abdominal pain (52.4%), diarrhea (33.3%), and cellulitis with bullae Formation (19%). Concurrent spontaneous bacterial peritonitis was determined in 10 cases, seven with positive ascites cultures. Antibiotic therapy (either cephalothin with gentamicin or ceftriaxone alone) cured most of the bacteremic episodes. The overall case-fatality rate was 23.8%, hut 75% of the deaths were observed in patients with skin manifestation. Conclusions: Patients with decompensated cirrhosis are susceptible to non-01 V. cholerae bacteremia and should not ingest raw sea food or expose skin wounds to salt water. A high index of suspicion and early administration of antibiotics may lower the mortality rate.     

The friction of explanted hip prostheses

Charnley prostheses, retrieved at revision surgery, were studied to assess the effects of friction on the total hip replacement procedure. Frictional resistance was measured using the Durham hip function simulator under both dry and lubricated conditions. The friction factor values (f) for the explanted prostheses were found to have a non- Gaussian distribution with medians of 0.13 [inter-quartile range (IQR) 0.10-0.16] and 0.06 (IQR 0.005-0.08) for dry and lubricated (n = 0.01 Pa s) regimes, respectively. New Charnley prostheses had values of f equal to 0.11 +/- 0.025 and 0.04 +/- 0.01 under the same conditions, and showed no large deviation from a Gaussian distribution. There was found to be a statistically significant difference in the medians of the friction factors for new and retrieved prostheses in the lubricated regime. Ingression of cement into the worn region of the cup was found to increase the friction factor significantly under dry conditions. There was no evidence of an increase in the friction factor or torque for those joints that had a loose socket with respect to those that were fixed at revision. A decrease in the frictional torque against number of cycles undergone by the joint in vivo may indicate that a fatigue-type process may have a role in the loosening of the socket. However, this relationship was found not to be significant for friction measured under lubricated conditions and it seems unlikely that the frictional torque generated in this type of prosthesis will contribute significantly to the long-term loosening of the socket.      

Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Hepatolithiasis in East Asia retrospective study

Hepatolithiasis is a major disease in Asia but differences in operative incidence between countries have not been examined. A retrospective study was conducted in Taiwan, Hong Kong, and Singapore, and the results were compared with those in Japan with the aim of defining factors involved in the etiology of the condition. In order to ensure uniformity of the data collected, the same form was used throughout the study and was completed by the same personnel after reviewing the patient's record and radiographs in each case. The years 1976–1980 were chosen for the study, since the newer methods of diagnosis such as ultrasound, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography became available during that period. The most significant finding was the difference in the relative prevalence of hepatolithiasis as a proportion of all gallstone cases in Taiwan, Hong Kong, and Singapore, where the majority of the population consisted of patients of Chinese descent. The highest prevalence, 53.5%, was found in Taiwan, while in Hong Kong it was 3.1% and in Singapore 1.7%. Environmental rather than ethnic factors are implicated in the cause of hepatolithiasis.Supported by Research Grant 504152 and 56043046 from the Ministry of Education, Japanese Government.