Increasing response rates from physicians in oncology research: a structured literature review and data from a recent physician survey.

Although the physician survey has become an important tool for oncology-focused health services research, such surveys often achieve low response rates. This mini-review reports the results of a structured review of the literature relating to increasing response rates for physician surveys, as well as our own experience from a survey of physicians as to their referral practices for suspected haematologic malignancy in the United States. PubMed and PsychINFO databases were used to identify methodological articles assessing factors that influence response rates for physician surveys; the results were tabulated and reviewed for trends. We also analysed the impact of a follow-up telephone call by a physician investigator to initial non-responders in our own mailed physician survey, comparing the characteristics of those who responded before vs after the call. The systematic review suggested that monetary incentives and paper (vs web or email) surveys increase response rates. In our own survey, follow-up telephone calls increased the response rate from 43.7% to 70.5%, with little discernible difference in the characteristics of early vs later responders. We conclude that in addition to monetary incentives and paper surveys, physician-to-physician follow-up telephone calls are an effective method to increase response rates in oncology-focused physician surveys.

Limits to research risks.

Risk-benefit assessment is a routine requirement for research ethics committees that review and oversee biomedical research with human subjects. Nevertheless, it remains unclear how to weigh and balance risks to research participants against the social benefits that flow from generating biomedical knowledge. In this article, we address the question of whether there are any reasonable criteria for defining the limit of permissible risks to individuals who provide informed consent for research participation. We argue against any a priori limit to permissible research risks. However, attention to the uncertainty of potential social benefit that can be derived from any particular study warrants caution in exposing prospective research participants to a substantial likelihood of serious harm.

Diagnosis of cystic fibrosis in the Republic of Ireland: epidemiology and costs.

There were four objectives in this study: (1) determine the incidence of cystic fibrosis (CF) in Ireland; (2) estimate the cost of diagnosing CF; (3) clarify the characteristics and outcomes of the nationwide diagnostic efforts and (4) identify disparities. Surveys were conducted to determine the number, methods, costs and outcomes for sweat tests in Ireland from 2001 through 2003. The results allowed us to determine that Ireland's CF incidence is the world's highest at 1:1353. The average cost for diagnosis was Euro 2663 per patient. Analyses of data in The Cystic Fibrosis Registry of Ireland revealed longer delays when diagnosis followed respiratory symptoms, rather than gastrointestinal signs, and also in girls compared to boys, particularly those presenting with respiratory symptoms. Although expenditures for diagnosing of CF in Ireland are relatively modest, the high incidence and age of diagnosis, as well as gender-related disparities, are sufficient to warrant investment in national newborn screening.

What do patients value in their hospital care? An empirical perspective on autonomy centred bioethics.

OBJECTIVE: Contemporary ethical accounts of the patient-provider relationship emphasise respect for patient autonomy and shared decision making. We sought to examine the relative influence of involvement in decisions, confidence and trust in providers, and treatment with respect and dignity on patients' evaluations of their hospital care. DESIGN: Cross-sectional survey. SETTING: Fifty one hospitals in Massachusetts. PARTICIPANTS: Stratified random sample of adults (N=27 414) discharged from a medical, surgical, or maternity hospitalisation between January and March, 1998. Twelve thousand six hundred and eighty survey recipients responded. MAIN OUTCOME MEASURE: Respondent would definitely be willing to recommend the hospital to family and friends. RESULTS: In a logistic regression analysis, treatment with respect and dignity (odds ratio (OR) 3.4, 99% confidence interval (CI) 2.8 to 4.2) and confidence and trust in providers (OR 2.5, CI 2.1 to 3.0) were more strongly associated with willingness to recommend than having enough involvement in decisions (OR 1.4, CI 1.1 to 1.6). Courtesy and availability of staff (OR 2.5, CI 2.1 to 3.1), continuity and transition (OR 1.9, CI 1.5 to 2.2), attention to physical comfort (OR 1.8, CI 1.5 to 2.2), and coordination of care (OR 1.5, CI 1.3 to 1.8) were also significantly associated with willingness to recommend. CONCLUSIONS: Confidence and trust in providers and treatment with respect and dignity are more closely associated with patients' overall evaluations of their hospitals than adequate involvement in decisions. These findings challenge a narrow emphasis on patient autonomy and shared decision making, while arguing for increased attention to trust and respect in ethical models of health care.

Quality of informed consent in cancer clinical trials: a cross-sectional survey.

BACKGROUND: Investigators have to obtain informed consent before enrolling participants in clinical trials. We wanted to measure the quality of understanding among participants in clinical trials of cancer therapies, to identify correlates of increased understanding, and to assess providers' beliefs about clinical research. We also sought evidence of therapeutic misconceptions in participants and providers. METHODS: We sent a standard questionnaire to 287 adult patients with cancer who had recently enrolled in a clinical trial at one of three affiliated institutions, and surveyed the provider who obtained each patient's consent. FINDINGS: 207 of 287 (72%) patients responded. 90% (186) of these respondents were satisfied with the informed consent process and most considered themselves to be well informed. Nevertheless, many did not recognise non-standard treatment (74%), the potential for incremental risk from participation (63%), the unproven nature of the treatment (70%), the uncertainty of benefits to self (29%), or that trials are done mainly to benefit future patients (25%). In multivariate analysis, increased knowledge was associated with college education, speaking only English at home, use of the US National Cancer Institute consent form template, not signing the consent form at initial discussion, presence of a nurse, and careful reading of the consent form. Only 28 of 61 providers (46%) recognised that the main reason for clinical trials is benefit to future patients. INTERPRETATION: Misconceptions about cancer clinical trials are frequent among trial participants, and physician/investigators might share some of these misconceptions. Efforts to educate providers and participants about the underlying goals of clinical trials are needed.

Inflammatory bowel disease associated with immune thrombocytopenic purpura in children.

OBJECTIVE: Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. METHODS: Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. RESULTS: The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/- 5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n = 6), intravenous immunoglobulin (n = 6), Rh o (D) intravenous immunoglobulin (n = 2), and splenectomy (n = 1). CONCLUSIONS: The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD.

Ambulatory estimates of maximal aerobic power from foot -ground contact times and heart rates in running humans.

Seeking to develop a simple ambulatory test of maximal aerobic power (VO(2 max)), we hypothesized that the ratio of inverse foot-ground contact time (1/t(c)) to heart rate (HR) during steady-speed running would accurately predict VO(2 max). Given the direct relationship between 1/t(c) and mass-specific O(2) uptake during running, the ratio 1/t(c). HR should reflect mass-specific O(2) pulse and, in turn, aerobic power. We divided 36 volunteers into matched experimental and validation groups. VO(2 max) was determined by a treadmill test to volitional fatigue. Ambulatory monitors on the shoe and chest recorded foot-ground contact time (t(c)) and steady-state HR, respectively, at a series of submaximal running speeds. In the experimental group, aerobic fitness index (1/t(c). HR) was nearly constant across running speed and correlated with VO(2 max) (r = 0.90). The regression equation derived from data from the experimental group predicted VO(2 max) from the 1/t(c). HR values in the validation group within 8.3% and 4.7 ml O(2) x kg(-1) x min(-1) (r = 0.84) of measured values. We conclude that simultaneous measurements of foot-ground constant times and heart rates during level running at a freely chosen constant speed can provide accurate estimates of maximal aerobic power.

Quality of informed consent: a new measure of understanding among research subjects.

BACKGROUND: The informed consent of participants is ethically and legally required for most research involving human subjects. However, standardized methods for assessing the adequacy of informed consent to research are lacking. METHODS AND RESULTS: We designed a brief questionnaire, the Quality of Informed Consent (QuIC), to measure subjects' actual (objective) and perceived (subjective) understanding of cancer clinical trials. The QuIC incorporates the basic elements of informed consent specified in federal regulations, assesses the therapeutic misconception (the belief that all aspects of a clinical trial are designed to directly benefit the subject), and employs the language and structure of the new National Cancer Institute template for informed consent documents. We modified the QuIC after receiving feedback from pilot tests with cancer research subjects, as well as validation from two independent expert panels. We then sent the QuIC to 287 adult cancer patients enrolled on phase I, II, or III clinical trials. Two hundred seven subjects (72%) completed the QuIC. To assess test-retest reliability, a random sample of 32 respondents was selected, of whom 17 (53%) completed the questionnaire a second time. The test-retest reliability was good with intraclass correlation coefficients of.66 for tests of objective understanding and.77 for tests of subjective understanding. The current version of the QuIC, which consists of 20 questions for objective understanding and 14 questions for subjective understanding, was tested for time and ease of administration in a sample of nine adult cancer patients. The QuIC required an average of 7.2 minutes to complete. CONCLUSIONS: The QuIC is a brief, reliable, and valid questionnaire that holds promise as a standardized way to assess the outcome of the informed consent process in cancer clinical trials.

Rehospitalization for respiratory syncytial virus among premature infants.

OBJECTIVES: New interventions to prevent respiratory syncytial virus (RSV) have recently become available. Clinical decisions about the use of these interventions require a better understanding of the incidence of and risk factors for RSV. We sought to characterize the epidemiology of severe RSV disease among premature infants and to identify high-risk subgroups. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California, July 1992 to April 1996. PARTICIPANTS: One thousand seven hundred twenty-one premature infants born at 23 to 36 weeks who were discharged from a neonatal intensive care nursery (NICU) within 12 months before the December to March RSV season. A secondary analysis included 769 infants discharged during the RSV season. OUTCOME MEASURES: Hospitalization for RSV. RESULTS: Of 1721 infants already home from the NICU at the start of the season, 3.2% were rehospitalized for RSV. In a multivariate model, risk factors for RSV hospitalization included gestation /=28 days of perinatal oxygen (OR, 3.7), and NICU discharge during September to November (OR, 2.7). Predicted risk of hospitalization varied by subgroup, ranging from 1.2% to 24.6%. Among 769 infants discharged from the NICU during the RSV season, 3.5% were rehospitalized for RSV during the same season; gestation and perinatal oxygen were not associated with admission. CONCLUSIONS: Most premature infants in this population were at less risk of severe RSV disease than previous studies in other populations have suggested. Preterm infants with a lower gestational age, a prolonged perinatal oxygen requirement, and NICU discharge within 3 months of the RSV season were most likely to require hospitalization for RSV disease. Cost-effectiveness analyses are needed to help define the role of available prophylactic interventions.

Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.

OBJECTIVES: To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. RESULTS: Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was /=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. CONCLUSION: In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.

Rehospitalization in the first two weeks after discharge from the neonatal intensive care unit.

BACKGROUND: High-risk newborns are known to have higher than average utilization of services after discharge from the neonatal intensive care unit (NICU). Most studies on this subject report aggregate data over periods ranging from 1 to 3 years postdischarge. Little is known about events that are temporally close to NICU discharge. OBJECTIVES: To characterize rehospitalizations within the first 2 weeks after discharge from six community NICUs. METHODS: We scanned electronic databases and reviewed the charts of rehospitalized infants from six NICUs in the Kaiser Permanente Medical Care Program. We subdivided infants into five groups based on gestational age (GA) and birth hospitalization length of stay (LOS): 1) >/=37 weeks' GA with <4 days LOS (n = 2593); 2) >/=37 weeks' GA with >/=4 days' LOS (n = 1133); 3) from 33 to 36 weeks' GA with <4 days' LOS (n = 545); 4) from 33 to 36 weeks' GA with >/=4 days' LOS (n = 1196); and 5) <33 weeks' GA (n = 587). We performed bivariate and multivariate analyses to identify predictors that might be useful for practitioners. RESULTS: There were 6054 newborns discharged alive from the six study NICUs between August 1, 1992 and December 31, 1995, and 99.5% of these infants remained in the health plan during the 2 weeks after NICU discharge. The overall rehospitalization rate was 2.72%, which is 20% higher than the rate among healthy term newborns in the Kaiser Permanente Medical Care Program (2.26%). The two most common reasons for rehospitalization were jaundice (62/165, 37.6%) and feeding difficulties (25/165, 15.2%). Infants with 33 to 36 weeks' GA and <4 days' LOS were rehospitalized at a significantly higher rate than were all other infants (5.69%); 71% of infants in this group were rehospitalized for jaundice. The following variables predicted rehospitalization in multivariate models: <33 weeks' GA (adjusted OR [AOR]: 1.88; 95% CI: 1.10-3.21), from 33 to 36 weeks' GA with <96 hours' LOS (AOR: 2.94; 95% CI: 1.87-4.62), and birth at facility B, which had the highest rehospitalization rate of the six facilities (AOR: 1.92; 95% CI: 1.39-2.65). CONCLUSIONS: The rate of rehospitalization among NICU graduates is higher than among healthy term infants. Most of the rehospitalizations among infants with from 33 to 36 weeks' GA and <4 days' LOS are for illnesses that are not life-threatening. Collaborative studies and new process and outcomes measures are needed to assess the effectiveness of follow-up strategies in high-risk newborns.

Spectrum of salivary gland disease in HIV-infected patients: characterization with Ga-67 citrate imaging.

The authors retrospectively reviewed 45 gallium-67 citrate scans of 28 patients infected with the human immunodeficiency virus (HIV). Abnormal salivary gland radiotracer activity was seen in 13 patients with diffuse infiltrative lymphocytosis syndrome (DILS), five patients with undifferentiated salivary gland disease (USD), and 10 patients with acquired immunodeficiency syndrome (AIDS). More DILS patients (54%) had intense gallium uptake than did the AIDS and USD patients combined (13%) (P less than .05). DILS patients had markedly elevated CD8 cell counts and moderately reduced CD4 cell counts, while AIDS patients had normal CD8 cell counts and markedly reduced CD4 cell counts. These differences were statistically significant (P less than .05). The authors recommend that DILS be considered in the differential diagnosis when abnormal, particularly intense, bilateral salivary gland gallium uptake occurs in HIV-infected patients. This disease is more likely to occur when circulating CD8 lymphocytosis is present, while AIDS is the more likely diagnosis when the patient has a normal CD8 cell count and a markedly depressed CD4 cell count.

Nd:YAG laser bipolar dissector--preliminary results.

We have developed a laser bipolar dissector (LBD) which uses the 1,064 nm Nd:YAG wavelength. The laser emits from the inner surface of the distal 7 mm of each probe made of synthetic sapphire. With low laser power (15-25 W), the bipolar provides hemostatic cutting of larger blood vessels. Animal experiments were carried out using New Zealand white rabbits. The LBD hemostatically cut through veins up to 5 mm and arteries up to 2 mm in diameter. Rebleeding did not occur. Transection of parenchymal organs such as liver and lung was easily performed with complete hemostasis. In chronic experiments a partial hepatectomy with splenectomy and left nephrectomy was performed using the LBD alone without any ligation. Up to 3 weeks postoperatively there were no direct complications related to using the LBD. In conclusion the LBD could perform a hemostatic transection of large vessels and might have clinical application in the dissection of vascular parenchymal organs.

Clinical application of the Nd:YAG laser bipolar dissector in intra-abdominal surgery.

A laser bipolar dissector (LBD) using a 1064 nm Nd:YAG laser energy source that provides hemostatic dissection using low-powered laser energy (15-25 W) has been developed. Clinical applications have included a partial hepatectomy (n = 5), a cholecystectomy (n = 4), an appendectomy, lymphnode dissection, and division of adhesions. The LBD was effective in resection of noncirrhotic liver and reduced the number of ligations required. There were no direct complications related to using the LBD. Operative time and blood loss were difficult to compare to conventional methods. The LBD may have applications for partial hepatectomies and other intra-abdominal operations.

Endoscopic contact Nd:YAG laser resectional vaporization (ECLRV) and esophageal dilatation (ED) in advanced malignant obstruction of the esophagus.

Malignant esophageal obstruction in patients with advanced and metastatic carcinoma is unsuitable for surgery. Palliative treatment must provide adequate swallowing with minimum complications in these often seriously ill patients. Twenty consecutive patients underwent endoscopic Nd:YAG contact laser resection and vaporization (ECLRV) and esophageal dilatation (ED) for advanced esophageal carcinoma since August, 1985. Average duration of the disease when first referred was 7.2 months. Tumor cell type was either squamous cell carcinoma (n = 11) or adenocarcinoma (n = 9). Tumor location was distal (n = 14), middle (n = 5), or upper (n = 2). Mean tumor length was 7.5 cm. Mean preoperative luminal diameter was 1 mm, with total obstruction in ten (50%) patients. The operative procedure in all patients was under general anesthesia with endotracheal tube intubation. Rigid and flexible endoscopes were both used as indicated. Mean postoperative luminal diameter was 15 mm. All but four were able to swallow fluids on the first postoperative day, followed by semisolids the next day without discomfort. Minor perforation was noted in three cases and managed in two conservatively. One more patient had difficulty in swallowing due to extra-esophageal compression, in spite of a technically successful laser therapy. Percutaneous endoscopic gastrostomy (PEG) was carried out in eight cases. Eleven patients were retreated successfully for recurrent obstruction and two were treated more than twice, at a mean of six-week intervals. Endoscopic contact laser resectional vaporization with esophageal dilatation was relatively safe and provided an improved quality of life in this preliminary study group, providing a mean survival of 18.5 weeks (range 2-50 weeks).

Laserthermia. A new method of interstitial local hyperthermia using the contact Nd:YAG laser.

Laserthermia is a new method of delivering interstitial local hyperthermia using a synthetic contact probe with a computer-controlled Nd:YAG laser to deliver both pulsed and continuous laser energy. The system allows an easily controllable increase in temperature (for example, from 42 to 43 degrees C) over a fixed period of time (for example, 20 minutes) to be delivered to tissue. A single or multiple channel system can be used depending on the volume of tissue to be treated. Tumor necrosis appears to be related to avascular infarction. Early clinical results support the beneficial therapeutic effects of Laserthermia in its oncologic applications.

Contact YAG laser system in abdominal surgery, in particular hepatic and pancreatic surgery.

The SLT contact Nd:YAG laser system offers a new method of obtaining a hemostatic incision through the anterior abdominal wall and a surgical tool for performing various intraabdominal resectional procedures. Advantages include reduction in intraoperative bleeding, reduced tissue damage, and tactile sensation with a reduction in laser power requirements. Sterile disposable laser scalpels, fibers, synthetic sapphire probes, and a user friendly laser system offer a new dimension in intraabdominal surgery, especially relating to liver and pancreatic surgery. Potentially, all general surgical procedures could use the SLT contact laser, which may, in the future, replace conventional electrocautery and the surgical steel scalpel. Cost containment and improved quality of care will probably be the driving forces for its acceptance.

Laser surgery in colonic and anorectal lesions.

Endoscopic laser therapy for diseases of gastrointestinal tract in general, and lesions of colon, rectum, and anus in particular, is in its infancy. Advances are expected to be made to define those lesions that are amenable to lasers and those that are not. In this process, it is hoped that the relative merits and demerits of the various modes of endoscopic therapy might be brought to light. With the advent of contact Nd:YAG laser technology, it is increasingly realized that such a mode of operation could be used to great advantage in both endoscopic and open surgery related to lower-gastrointestinal tract diseases. Furthermore, contact Nd:YAG laser therapy definitely appears to be efficient and safe and compares favorably with other therapies available. How such an effective modality should be sequenced in combination with other available therapies has yet to be worked out. There is more to be done in this arena, which holds high promises.