Enteroviral infection in patients treated with rituximab for non-Hodgkin lymphoma: a case series and review of the literature.

In recent years, anti-CD20 antibodies have been increasingly used to treat lymphoproliferative and immune disorders. Chronic viral infections are infrequently reported in patients receiving these therapies. Enteroviral infection can cause life-threatening meningoencephalitis and other systemic chronic syndromes in immune deficient patients. We describe the clinical courses and outcomes of 6 patients from 2 tertiary care institutions who developed chronic enteroviral infection with neurological manifestations, after combined chemoimmunotherapy with rituximab for B-cell lymphoma. We review the literature that includes 10 sporadic reported cases of chronic enteroviral meningoencephalitis attributed to rituximab therapy. It is a rare disease, and its diagnosis is often elusive. We propose that low immunoglobulin G levels are the main risk factor for developing chronic enteroviral infection and emphasize the need for a high index of suspicion, early diagnosis, and intervention in this iatrogenic and potentially fatal complication.

Live birth sex ratios and father's geographic origins in Jerusalem, 1964-1976.

OBJECTIVE: To examine whether ancestry influenced sex ratios of offspring in a birth cohort before parental antenatal sex selection influenced offspring sex. METHODS: We measured the sex ratio as the percent of males according to countries of birth of paternal and maternal grandfathers in 91,459 live births from 1964 to 1976 in the Jerusalem Perinatal Study. Confidence limits (CI) were computed based on an expected sex ratio of 1.05, which is 51.4% male. RESULTS: Of all live births recorded, 51.4% were male. Relative to Jewish ancestry (51.4% males), significantly more males (1,761) were born to Muslim ancestry (54.5, 95% CI = 52.1-56.8, P = 0.01). Among the former, sex ratios were not significantly associated with paternal or maternal age, education, or offspring's birth order. Consistent with a preference for male offspring, the sex ratio decreased despite increasing numbers of births over the 13-year period. Sex ratios were not affected by maternal or paternal origins in North Africa or Europe. However, the offspring whose paternal grandfathers were born in Western Asia included fewer males than expected (50.7, 50.1-51.3, P = 0.02), whether the father was born abroad (50.7) or in Israel (50.8). This was observed for descendents of paternal grandfathers born in Lebanon (47.6), Turkey (49.9), Yemen & Aden (50.2), Iraq (50.5), Afghanistan (50.5), Syria (50.6), and Cyprus (50.7); but not for those from India (51.5) or Iran (51.9). The West Asian group showed the strongest decline in sex ratios with increasing paternal family size. CONCLUSIONS: A decreased sex ratio associated with ancestry in Western Asia is consistent with reduced ability to bear sons by a subset of Jewish men in the Jerusalem cohort. Lower sex ratios may be because of pregnancy stress, which may be higher in this subgroup. Alternatively, a degrading Y chromosome haplogroup or other genetic or epigenetic differences on male germ lines could affect birth ratios, such as differential exposure to an environmental agent, dietary differences, or stress. Differential stopping behaviors that favor additional pregnancies following the birth of a daughter might exacerbate these lower sex ratios.

Long-term efficacy of Paula method as compared with pelvic floor muscle training for stress urinary incontinence in women: a 6-month follow-up.

PURPOSE: The purpose of this study was to examine the long-term efficacy of an exercise regimen based on circular muscle strengthening (Paula method) as opposed to pelvic floor muscle training (PFMT) on stress urinary incontinence symptoms at 6 months postintervention. SUBJECTS AND SETTING: Of 240 women who had initially participated in a randomized clinical trial, 143 women suffering from stress urinary incontinence participated in this follow-up study. METHODS: Subjects participated in a randomized controlled clinical trial comparing 2 exercise programs (12 private Paula lessons vs 6 group PFMT lessons) over a 12-week period. Of these, 143 women took part in the follow-up study: 64 from the Paula group and 79 from the PFMT group. Six-month follow-up data were gathered via telephone interviews. RESULTS: No significant deterioration in stress urinary incontinence symptoms occurred 6 months after completion of the interventions in either group. We found a statistically significant difference between the groups with regard to reported frequency of urinary leakage; 25 of subjects (39.7%) allocated to the Paula method reported a low frequency rate of incontinence episodes upon completion of the study as compared to 18 (22.8%) in the PFMT group (P = .03). Forty-nine of the 64 women in the Paula group (76.6%) and 62 of the 79 women in the PFMT group (78.5%) reported that they continued exercising 6 months after completion of the trial (P = .8). CONCLUSIONS: Both intervention methods reduced frequency of urinary incontinence over a 6-month period. Long-term adherence was similar in both groups. Pelvic floor muscle training was associated with fewer sessions and decreased cost and fewer lessons needed as compared with the Paula method. Nevertheless, results also suggest that the Paula method achieves a lower frequency of urinary leakage than PFMT.

Cancer risk after exposure to treatments for ovulation induction.

Uncertainty continues as to whether treatments for ovulation induction are associated with increased risk of cancer. The authors conducted a long-term population-based historical cohort study of parous women. A total of 15,030 women in the Jerusalem Perinatal Study who gave birth in 1974-1976 participated in a postpartum survey. Cancer incidence through 2004 was analyzed using Cox's proportional hazards models, controlling for age and other covariates. Women who used drugs to induce ovulation (n = 567) had increased risks of cancer at any site (multivariate hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.06, 1.74). An increased risk of uterine cancer was found among women treated with ovulation-inducing agents (HR = 3.39, 95% CI: 1.28, 8.97), specifically clomiphene (HR = 4.56, 95% CI: 1.56, 13.34). No association was noted between use of ovulation-inducing agents and ovarian cancer (age-adjusted HR = 0.61, 95% CI: 0.08, 4.42). Ovulation induction was associated with a borderline-significant increased risk of breast cancer (multivariate HR = 1.42, 95% CI: 0.99, 2.05). Increased risks were also observed for malignant melanoma and non-Hodgkin lymphoma. These associations appeared stronger among women who waited more than 1 year to conceive. Additional follow-up studies assessing these associations by drug type, dosage, and duration are needed.

Consanguinity and birth defects in the jerusalem perinatal study cohort.

BACKGROUND: While parental consanguinity is known to increase the risk of birth defects in offspring, it is hard to quantify this risk in populations where consanguinity is prevalent. METHODS: To support ongoing studies of cancer and of psychiatric disease, we studied relationships of consanguinity to 1,053 major birth defects in 29,815 offspring, born in 1964-1976. To adjust for confounding variables (geographic origin, social class and hospital), we constructed logistic regression models, using GEE to take into account correlations between sibs. Odds ratios (ORs) and 95% confidence limits were estimated in comparison to a reference group of offspring with grandfathers born in different countries. RESULTS: With 10.1% of offspring having consanguineous parents, the adjusted OR for major birth defect was 1.41 (1.12-1.74). Offspring of marriages between uncles-nieces, first cousins and more distant relatives showed adjusted ORs of 2.36 (0.98-5.68), 1.59 (1.22-2.07) and 1.20 (0.89-1.59) respectively. For descendents of grandfathers born in the same country, but not known to be related, the OR was 1.05 (0.91-1.21); these showed increased risk associated with ancestries in Western Asia (1.27, 1.04-1.55, p < 0.02) or Europe (1.13, 0.79-1.80). CONCLUSIONS: A strong association of consanguinity with poverty and low education points to the need to avoid exposure to environmental hazards in these families.

Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study.

BACKGROUND: Diabetes is known to be associated with cancer of the pancreas, though there is some debate as to whether it is a cause or a consequence of the disease. We investigated the incidence of pancreatic cancer in a cohort of 37926 Israeli women followed for 28-40 years for whom information on diabetes had been collected at the time they gave birth, in 1964-1976, in Jerusalem. There were 54 cases of pancreatic cancer ascertained from the Israel Cancer Registry during follow-up. METHODS: We used Cox proportional hazards models to adjust for age at baseline and explore effects of other risk factors, including ethnic groups, preeclampsia, birth order and birth weight of offspring. RESULTS: We observed no cases of pancreatic cancer in the women with insulin dependent diabetes; however, there were five cases in the women with gestational diabetes. The interval between the record of diabetes in pregnancy and the diagnosis of pancreatic cancer ranged from 14-35 years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1 (95% confidence interval, 2.8-18.0). CONCLUSION: We conclude that gestational diabetes is strongly related to the risk of cancer of the pancreas in women in this population, and that gestational diabetes can precede cancer diagnosis by many years.

Paternal age and spontaneous abortion.

OBJECTIVE: To evaluate the influence of paternal age upon spontaneous abortion. METHODS: This case-control study of 13,865 women draws on data from women's antenatal or postpartum interviews in the Jerusalem Perinatal Study, a population-based cohort derived from 92,408 births in 1964-1976. Case women (n=1,506) reported spontaneous abortion in the pregnancy preceding the interview; they were compared with women reporting live births in their previous pregnancy (n=12,359). Logistic regression was used to adjust for maternal age, maternal diabetes, maternal smoking, history of spontaneous abortions before the index pregnancy, parity at interview, and interval between the index pregnancy and the interview. RESULTS: The adjusted odds ratio for spontaneous abortion was 0.59 (95% confidence interval 0.45-0.76, P< .0001) for pregnancies conceived from fathers aged younger than 25 years compared with those from fathers aged 25-29 years. For fathers age 40 years or older the odds ratio for spontaneous abortion was 1.6 (95% confidence interval 1.2-2.0, P=.0003) when compared with the same reference group. CONCLUSION: Increasing paternal age is significantly associated with spontaneous abortion, independent of maternal age and multiple other factors.

Determinants of the use of complementary therapies by patients with cancer.

PURPOSE: We performed a survey of Israeli oncology patients to examine the extent of their use of complementary therapies (CT) and to compare sociodemographic, psychologic, and medical characteristics, attitudes, and quality of life of users and nonusers of CT. PATIENTS AND METHODS: Questionnaires were administered to 1,027 patients attending ambulatory and inpatient hematology or oncology facilities at three hospitals. Medical information was extracted from charts. Univariate and multivariate comparisons of users and nonusers of CT were performed. RESULTS: A total of 526 participants (51.2%) had used CT since their diagnosis, and 357 patients (34.9%) had used CT recently (in the past 3 months). Factors that multivariate analysis found to be significantly associated (P <.05) with recent CT use were as follows: female sex; age 35 to 59 years; more education; coming to the hospital by private car; advanced disease status; having a close friend or a relative with cancer; and attending support groups or individual counseling. After controlling for these factors, individually examined psychosocial variables associated with recent CT use included the following (odds ratios [OR] with 95% confidence intervals [CI]): needs unmet by conventional medicine (OR, 2.76; 95% CI, 1.95 to 3.89); helplessness (OR, 1.39; 95% CI, 1.0 to 1.91); incomplete trust in the doctor (OR, 1.49; 95% CI, 1.08 to 2.06); and changed outlook or beliefs since the diagnosis of cancer (OR, 1.47; 95% CI, 1.07 to 2.02). Functional quality of life (including physical, emotional, social, and role function) and symptom (fatigue and diarrhea) scores were significantly worse for recent CT users compared with nonusers, controlling for age, sex, and current disease status. CONCLUSION: Characteristics associated with CT use include age, sex, education, and advanced disease. Significant associations between CT use and attending supportive psychotherapy, unmet needs, helplessness, and worse emotional and social function indicate considerable distress, suggesting that increased attention to psychosocial needs within oncologic settings is warranted.

Management of severe hypokalemia in hospitalized patients: a study of quality of care based on computerized databases.

BACKGROUND: While administrative databases are used to assess general indicators of quality of care, a detailed audit of the process of clinical care usually requires review of hospital medical records. OBJECTIVE: To evaluate the feasibility of assessing the management of severe hypokalemia using computerized administrative and laboratory databases. METHODS: The study included all patients hospitalized in 1997 who experienced serum potassium levels of less than 3.0 mmol/L at Hadassah University Hospital, Jerusalem, Israel, a tertiary care center. Using the computerized databases, we measured the following: (1) whether a subsequent serum potassium test was performed, (2) time to the subsequent test and to normalization of the serum potassium level, (3) achievement of normokalemia, and (4) in-hospital mortality. In a random subsample of 100 patients, these measures were compared with the blinded assessment of the quality of medical management of hypokalemia, as determined from medical records, using predetermined criteria for adequate management. RESULTS: The computerized databases revealed that severe hypokalemia occurred in 866 patients (2.6% of the yearly hospitalizations): 55 patients (6.4%) had no subsequent serum potassium levels measured, and 260 (30.0%) were discharged from the hospital with a subnormal potassium level. The mean time to a subsequent test was 20 hours, and to normokalemia, 50 hours; both intervals varied by department. In-hospital mortality was 20.4%, or 10-fold that of the entire hospitalized population. A review of hospital medical records revealed inadequate clinical management of hypokalemia in 24%, which was associated with nonperformance of a subsequent test (likelihood ratio, 8.4), failure to normalize the serum potassium level (likelihood ratio, 4.2), discharge from the hospital with a subnormal potassium level (likelihood ratio, 2.1), and in-hospital death (likelihood ratio, 2.5), all of which could be determined by the computerized databases. CONCLUSIONS: The computerized laboratory database is useful in ascertaining the prevalence of severe hypokalemia and in assessing shortcomings in its management. Databases can be used to derive valid and efficient measures of the quality of the clinical management of electrolyte disorders.

Age-associated risks of prophylactic anticoagulation in the setting of hip fracture.

PURPOSE: Controversy exists as to whether patient age, either independently or as a marker of concomitant illness or medication use, is associated with the dose or complication rate of warfarin prophylaxis. The aim of this study was to assess this relationship in patients receiving warfarin prophylaxis after hip fracture repair. PATIENTS AND METHODS: We undertook a retrospective cohort study of 215 patients 55 years of age or greater who underwent surgery for a fractured hip between January 1, 1990, and December 31, 1991, and received warfarin prophylaxis. The mean age was 78.9 (SD 9.5) years. The average daily warfarin dose, the decrease in hemoglobin in the postoperative period, and the rate of bleeding complications were assessed. RESULTS: Elderly patients required a significantly lower average daily warfarin dose than younger patients. This effect persisted even after controlling for the number of medical conditions, number of medications on admission, proportion of time the international normalized ration (INR) was in therapeutic range, and gender. Postoperative hemoglobin decrease was associated with patient age as well as with the use of antibiotics postoperatively. Factors associated with bleeding complications included a history of alcohol abuse and a smaller proportion of time spent in the targeted anticoagulant range. CONCLUSIONS: Older age itself and not as a marker for polypharmacy or increased number of medical conditions is associated with lower requirements for warfarin and a greater hemoglobin decrease postoperatively even when the proportion of time the INR fell within the therapeutic range is controlled. Advanced patient age, in this study, was not associated with an increased incidence of bleeding complications.

Two-way referral bias: evidence from a clinical audit of lymphoma in a teaching hospital.

The objective of this study was to evaluate the effect of referral bias in a clinical audit of lymphoma in a university hospital. We compared demographic and clinical characteristics as well as survival for Jerusalem residents (local) and referred (distant) patients diagnosed from 1987 to 1992 and treated in our institution. Referred patients were younger (p < 0.0001), and less likely to be immigrants (p < 0.0001), than local patients. Aggressive non-Hodgkin's lymphomas (NHL) were more common in the referred population (p = 0.015). Survival for Hodgkin's disease was consistently better for local patients, but for patients with NHL the findings were reversed. In this study referred patients differed in their clinical and sociodemographic characteristics but did not consistently exhibit a worse outcome than that of local patients. The unpredictable nature of referral bias may be due to better functional status or resources among referred patients, or to selective referral for procedures such as bone marrow transplantation. While reports on the natural history of disease from tertiary institutions may be biased by referral patterns, the direction of the bias is not uniform.

Chlamydia pneumoniae and acute myocardial infarction in Jerusalem.

BACKGROUND: A number of studies in European and North American populations have reported associations between Chlamydia pneumoniae seropositivity and coronary heart disease (CHD). Our objective was to assess the association of IgG and IgA antibodies to C. pneumoniae with acute myocardial infarction (MI) in a population-based case-control study in a Middle Eastern country. METHODS: Eligible cases aged 25-64 with a first acute MI were ascertained through an active surveillance system in Jerusalem hospitals between 1987 and 1989 (85% response). Controls were Jerusalem residents aged 25-64 sampled from the national population registry (83% response). Data on sociodemographic variables, CHD history and risk factors were collected by interview. Chlamydia serology, available for 93% of eligible participants, was performed by microimmunofluorescence on frozen stored samples using the TWAR antigen. Altogether, 251 male and 51 female cases, and 324 male and 162 female controls were analysed. RESULTS: Overall, high IgG titres (> or = 128) were not associated with increased risk of acute MI (Odds ratio [OR] = 0.74 for men [95% confidence interval (CI): 0.47-1.17] and 0.91 for women [95% CI: 0.43-1.94]); neither were high IgA titres (> or = 80) (OR = 1.11 for men [95% CI: 0.71-1.73] and 1.15 for women [95% CI: 0.33-4.0]). At IgG and IgA titres of > 32 and > 20 respectively there was also no relation. CONCLUSIONS: An association of C. pneumoniae seropositivity with acute MI was not confirmed in this population with a very high IgG seropositivity prevalence of 84% in males and 69% in females. However, we cannot exclude the possibility that a postulated recent outbreak obscured an association with chronic C. pneumoniae infection.

A comparison of clinical criteria for the diagnosis of veno-occlusive disease of the liver after bone marrow transplantation.

Two major studies have established clinical criteria for the diagnosis of veno-occlusive disease of the liver (VOD) after bone marrow transplantation (BMT). McDonald and co-workers defined VOD as the onset of two of the following occurring before day 30 post-BMT: (a) jaundice (bilirubin > 27 mmol/l), (b) tender hepatomegaly, and (c) ascites or weight gain. In contrast, Jones and co-workers defined VOD as the onset, before day 21 post-BMT, of hyperbilirubinemia (bilirubin > 34 mmol/l) as well as two of the following: (a) hepatomegaly, (b) ascites, and (c) weight gain. We retrospectively reviewed the occurrence of VOD in 101 patients transplanted primarily for hematologic malignancies between 1979 and 1990, applying both sets of criteria. Of the 101 patients, eight (7.9%) fulfilled the Jones criteria whereas 32 (31.7%) had VOD according to the McDonald criteria (p < 0.001). Early mortality (prior to 50 days post-BMT) was 75% (6/8) in patients who fulfilled the Jones criteria but only 28.1% (9/32) in the McDonald group (p < 0.005). Overall, mortality in each group was 75% (6/8) and 65.6% (21/32), respectively. All of the six patients with VOD according to the Jones criteria who died had evidence of hepatic failure. Of the 32 patients who fulfilled the McDonald criteria, eight have also fulfilled the Jones criteria and are described above. Of the remaining 24 patients, 22 had complete resolution of VOD as defined by these criteria within 50 days of BMT, none developed hepatic failure, and 15 died.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors associated with survival in patients with progressive disease following autologous transplant for lymphoma.

Our objectives were to assess survival and predictors for survival among lymphoma patients whose disease had progressed after autologous bone marrow (ABMT) or stem cell transplantation (ASCT). Patients transplanted at Hadassah University Hospital between October 1983 and February 1999 were included. We compared survival of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) after relapse or progression. Predictors for survival were assessed in a multivariate model. Of 88 transplanted patients with HD and 152 with NHL, relapse/progression occurred in 27 (31%) and 75 (49%), respectively. Median survival postrelapse was 25 months for HD and 7.5 months for NHL (P=0.12). Seven relapsed patients with HD (26%) and 10 (13%) with NHL survived >4 years. In NHL, longer postrelapse survival was associated with indolent histologies (P=0.007). On multivariate analysis, factors associated with survival included attainment of remission postrelapse (for both diseases), use of prophylactic immunotherapy (for HD), LDH level and time from transplant to relapse (for NHL). The short-term prognosis for patients with disease progression postautologous transplant may be somewhat better for HD compared to NHL. Long-term survival is poor in both diseases. However, the survival times in the current study are twice as long as those previously reported. Treatment regimens with the potential for achieving remission may have an impact on survival.

Unusual cytomegalovirus complications after autologous stem cell transplantation for large B cell lymphoma: massive gastrointestinal hemorrhage followed by a communicating hydrocephalus.

Unusual cytomegalovirus (CMV)-related complications were seen after autologous stem cell transplantation (SCT) in a 50-year-old patient with diffuse large B cell lymphoma. One month after SCT, the patient developed life-threatening upper gastrointestinal tract (GIT) bleeding with several episodes of hemorrhagic shock. Endoscopy and subsequent explorative laparotomy revealed deep-seated bleeding ulcers containing intracellular CMV inclusion bodies distributed extensively in the GIT, from the lower esophagus to the small bowel. Later, she developed gradual loss of consciousness with communicating hydrocephalus which was possibly secondary to CMV-induced ventriculitis. She recovered completely after insertion of a ventriculostomy and subsequent V-P shunt.

Probabilistic reasoning and clinical decision-making: do doctors overestimate diagnostic probabilities?

BACKGROUND: The "threshold approach" is based on a physician's assessment of the likelihood of a disease expressed as a probability. The use of Bayes' theorem to calculate disease probability in patients with and without a particular characteristic, may be hampered by the presence of subadditivity (i.e. the sum of probabilities concerning a single case scenario exceeding 100%). AIM: To assess the presence of subadditivity in physicians' estimations of probabilities and the degree of concordance among doctors in their probability assessments. DESIGN: Prospective questionnaire. METHODS: Residents and trained physicians in Family Medicine, Internal Medicine and Cardiology (n = 84) were asked to estimate the probability of each component of the differential diagnosis in a case scenario describing a patient with chest pain. RESULTS: Subadditivity was exhibited in 65% of the participants. The total sum of probabilities given by each participant ranged from 44% to 290% (mean 137%). There was wide variability in the assignment of probabilities for each diagnostic possibility (SD 16-21%). DISCUSSION: The finding of substantial subadditivity, coupled with the marked discordance in probability estimates, questions the applicability of the threshold approach. Physicians need guidance, explicit tools and formal training in probability estimation to optimize the use of this approach in clinical practice.

Likelihood ratios: getting diagnostic testing into perspective.

In modern medicine, sophisticated laboratory tests and imaging studies are often emphasized at the expense of history and physical examination, rather than complementing clinical assessment. Ancillary testing often fails to advance the diagnostic process, and increases patient risk and the expense of medical care. The relative value of clinical evaluation and technological methods is rarely considered, and the power of the clinical evaluation is therefore underestimated. The likelihood ratio (LR) is a semiquantitative measure of the performance of diagnostic tests which indicates how much a diagnostic procedure modifies the probability of disease, and is calculated from the sensitivity and specificity of the test (or directly from the change in probability associated with the test result). We review the performance of frequently-used tests by their LRs, and compare them to the power of clinical assessment, with clinical cases to illustrate the application of LRs in the diagnostic process. The discriminative power of clinical assessment and ancillary tests is often similar, and the combination of the two greatly increases accuracy in the diagnostic process. Clinical assessment is indeed frequently more informative than current technical modalities. LRs assist in putting the value of testing in proper perspective. Practice in evaluating pre-test probabilities of disease and in the application of LRs should be enhanced in medical training.

Salvage chemotherapy using a combination of fludarabine and cyclophosphamide for refractory or relapsing indolent and aggressive non-Hodgkin's lymphomas.

The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) after primary therapy is poor and multi-drug salvage treatments are associated with less than 60% response rates, usually of short duration. Here we report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP-Cy) combination as a salvage failure regimen in refractory and relapsing low-grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had received up to 4 regimens prior to therapy with FAMP-Cy were treated with fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving complete responses (CR) and 7 partial responses (PR). All patients with low-grade NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR lasting for a median of 5 months. The main toxicity encountered was moderate myelosuppression. Three patients had febrile neutropenia, one had drug-induced fever and a single patient developed severe neurotoxicity. Opportunistic infections due to lymphopenia were not seen. The combination of fludarabine and cyclophosphamide used as a salvage regimen showed an impressive response in a small group of heavily pretreated low-grade NHL patients who had previously received a large number of prior regimens. FAMP-Cy had limited effect in a similar group of intermediate-grade NHL patients. Results with this "failure" regimen are encouraging, however further studies are needed in order to confirm these observations in a larger series of patients.

Human menopausal gonadotropin and the risk of epithelial ovarian cancer.

OBJECTIVE: To determine whether women with epithelial ovarian cancer are more likely to have been exposed to fertility drugs, and in particular hMG, than healthy population controls. DESIGN: A nationwide case-control study. PATIENTS: Two hundred living women 36 to 64 years of age, with a histologically confirmed diagnosis of primary invasive or borderline epithelial ovarian cancer that was first diagnosed and reported to the Israel Cancer Registry between January 1, 1990 and September 1, 1993 were enrolled. There were 164 (82%) invasive and 36 (18%) borderline epithelial ovarian tumors among the 200 cases. The controls were 408 women from the same dialing areas selected by random digit dialing. Cases and controls were interviewed using a standard questionnaire. A multivariate logistic model was used to assess the association of fertility drug use and ovarian cancer, controlling for variables found to be statistically associated with this outcome on univariate analysis. RESULTS: Twenty-four women with epithelial ovarian cancer (12%) and 29 healthy controls (7.1%) reported that they had used any fertility drug (adjusted odds ratio [OR] 1.31; 95% confidence interval [CI] 0.63 to 2.74). Among cases and controls, respectively, 22 and 24 reported that they had used hMG alone or in combination with clomiphene citrate (adjusted OR 1.42, 95% CI 0.65 to 3.12), and 11 and 6 reported that they had used hMG alone (adjusted OR 3.19, (95% CI 0.86 to 11.82). The risk was increased particularly in the subgroup of women with borderline ovarian tumors who had used hMG (adjusted OR 9.38, 95% CI 1.66 to 52.08). CONCLUSIONS: We conclude that the use of ovulation induction agents, in particular hMG, may increase the risk of epithelial ovarian tumors.

Analysis and impact of infectious disease consultations in a general hospital.

During an 18-month period, data from all patients in whose care our infectious diseases (ID) service was involved, were recorded in a computerized database. A total of 4184 new consultations was recorded. The consultations were solicited by the patients' physicians in 3326 cases (80%) and initiated by the ID service in the remainder. The purpose of the consultations was diagnosis (14%), therapy (39%), both diagnosis and therapy (40%), and prophylaxis (6%). Two thousand and ninety-four consultations (50%) were performed at the bedside, and the others by personal or telephone discussion. ID consultation was given in more than 10% of admitted patients in six departments, 46% of the admissions in the ICU, and 6.9/100 hospitalized patients. Recommendations included: antibiotic manipulation (i.e., initiation, change or discontinuation of antibiotic treatment) (51%); performance of tests (13%); performance of diagnostic or therapeutic procedures (5%); prophylaxis (4%) or no change in management (26%). Analysis of the solicited vs unsolicited consultations and of the bedside vs telephone consultations revealed that sub-groups of consultations differ significantly from each other in many aspects. Recording of consultations enables the ID service to evaluate its activity and to direct efforts to departments with high rates of infectious diseases and/or antimicrobial usage.