Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.

An Experimental Slope Method for a More Accurate Measurement of Relative Radiation Doses using Radiographic and Radiochromic Films and Its Application to Megavoltage Small-Field Dosimetry.

PURPOSE: An experimental method using the linear portion of the relative film dose-response curve for radiographic and radiochromic films is presented, which can be used to determine the relative depth doses in a variety of very small, medium, and large radiation fields and relative output factors (ROFs) for small fields. MATERIALS AND METHODS: The film slope (FS) method was successfully applied to obtain the percentage depth doses (PDDs) for external beams of photon and electrons from a Synergy linear accelerator (Elekta AB, Stockholm, Sweden) under reference conditions of 10 cm × 10 cm for photon beam and nominal 10 cm × 10 cm size applicator for electron beam. For small-field dosimetry, the FS method was applied to EDR2 films (Carestream Health, Rochester, NY) for 6 MV photon beam from a linac (Elekta AB, Stockholm, Sweden) and small, circular radiosurgery cones (Elekta AB, Stockholm, Sweden) with diameters of 5, 7.5, 10, 12.5, and 15 mm. The ROFs for all these cones and central axis PDDs for 5, 10, and 15 mm diameter cones were determined at source-to-surface distance of 100 cm. The ROFs for small fields of CyberKnife system were determined using this technique with Gafchromic EBT3 film (Ashland, NJ, USA). The PDDs and ROFs were compared with ion chamber (IC) and Monte Carlo (MC) simulated values. RESULTS: The maximum percentage deviation of PDDFS with PDDIC for 4, 6, and 15 MV photon beams was within 1.9%, 2.5%, and 1.4%, respectively, up to 20-cm depth. The maximum percentage deviation of PDDFS with PDDIC for electron beams was within 3% for energy range studied of 8-15 MeV. The gamma passing rates of PDDFS with PDDIC were above 96.5% with maximum gamma value of >2, occurring at the zero depths for 4, 6, and 15 MV photons. For electron beams, the gamma passing rates between PDDFS with PDDIC were above 97.7% with a maximum gamma value of 0.9, 1.3, and 0.7 occurring at the zero depth for 8, 12, and 15 MeV. For small field of 5-mm cone, the ROFFS was 0.665 ± 0.021 as compared to 0.674 by MC method. The maximum percentage deviation between PDDFS and PDDMC was 3% for 5 mm and 10 mm and 2% for 15 mm cones with 1D gamma passing rates, respectively, of 95.5%, 96%, and 98%. For CyberKnife system, the ROFFS using EBT3 film and MC published values agrees within 0.2% for for 5 mm cone. CONCLUSIONS: The authors have developed a novel and more accurate method for the relative dosimetry of photon and electron beams. This offers a unique method to determine PDD and ROF with a high spatial resolution in fields of steep dose gradient, especially in small fields.

Investigation of Internal Target Volumes Using Device and Deviceless Four-dimensional Respiratory Monitoring Systems for Moving Targets in Four-dimensional Computed Tomography Acquisition.

AIMS AND OBJECTIVES: The influence of target motion on the reconstructed internal target volume (ITV) for device-based (DB) external surrogate system and Smart deviceless (DL) 4-dimensional (4D) system were compared in a controlled phantom experiment. The volumetric changes in reconstructed ITVs from the average intensity projection (AveIP) images using DB method (Anzai Respiratory Gating System, ANZAI MEDICAL CO., LTD, Japan) and DL method (Smart deviceless 4D system by GE Medical Systems (Chicago, USA)) with the theoretical true volume (ITVth) for moving target with the increasing target motion in anterior-posterior (A-P), lateral (left-right [L-R]) and inferior-superior (S-I) directions were assessed. MATERIALS AND METHODS: 4D computed tomography (4DCT) of CIRS dynamic phantom (Computerized Imaging Reference Systems Inc., Norfolk, VA, USA) with 2.5 cm diameter spherical target of volume 8.2 cc programmed to move in a cos4(x) motion pattern placed in the lung volume were acquired for various target motion pattern using DB and DL method of gating. AveIP images of 10 phase binned image sets were generated and ITVs were delineated. RESULTS: The maximum absolute percent differences between ITVave and ITVth for DL and DB methods were 15.91% and 4.94 % respectively for target motion of 5 mm in AP with 15 mm S-I direction. When the S-I motion was decreased to 10 mm, the observed % difference of the ITVs were also decreased to 12.5% and 0.3% for DL and DB method. When the lateral [L-R] motion was varied from 0 mm to 5 mm for S-I motion of 5 mm to 15 mm, the differences in the ITVs were significant (P = 0.004) with the maximum absolute percent difference of 18.61% and 4.94 % for DL and DB gating. With the simultaneous motion of the target in all the 3 directions, the difference in the reconstructed ITVs were statistically significant for DL method (P = 0.0002) and insignificant for DB method (P = 0.06) with an average increase of 10% in ITVDL against 2% in the ITVDB. The difference in ITVDL was significant for the target motion above 3 mm in A-P and L-R directions for S-I movement of above 10 mm (P = 0.0002). However, for low excursions of the target movement, no significant difference in the ITVs were observed (P > 0.06). In general, ITVDBs were closer to the ITVth (within 7.8%) than ITVDL (18.61%). CONCLUSION: The results showed that the DL method is an effective way of image sorting in 4D acquisition for smaller target excursion. When the target motion exceeds 3 mm in A-P and L-R directions with S-I more than 10 mm, DB method is the choice due to its accuracy in reproducing the absolute target volume.

A prospective, randomized, comparison study on effect of perioperative use of chloride liberal intravenous fluids versus chloride restricted intravenous fluids on postoperative acute kidney injury in patients undergoing off-pump coronary artery bypass grafting surgeries.

CONTEXT AND AIMS: Off-pump coronary artery bypass graft (OPCABG) is a form of CABG surgery. It is performed without the use of cardiopulmonary bypass machine as a surgical treatment for coronary heart disease. Acute kidney injury (AKI) is one of the common postoperative complications of OPCABG. Previous studies suggest important differences related to intravenous fluid (IVF) chloride content and renal function. We hypothesize that perioperative use of chloride restricted IVFs may decrease incidence and severity of postoperative AKI in patients undergoing OPCABG. METHODS: Six hundred patients were randomly divided into two groups of 300 each. In Group A (n = 300), chloride liberal IVFs, namely, hydroxyethyl starch (130/0.4) in 0.9% normal saline (Voluven), 0.9% normal saline, and Ringer's lactate were used for perioperative fluid management. In Group B (n = 300), chloride-restricted IVFs, namely, hydroxyethyl starch (130/0.4) in balanced colloid solution (Volulyte) and balanced salt crystalloid solution (PlasmaLyte A), were used for perioperative fluid management. Serum creatinine values were taken preoperatively, postoperatively at 24 h and at 48 h. Postoperative AKI was determined by AKI network (AKIN) criteria. RESULTS: In Group A, 9.2% patients and in Group B 4.6% patients developed Stage-I AKI determined by AKIN criteria which was statistically significant (P < 0.05). CONCLUSION: Perioperative use of chloride restricted IVF was found to decrease incidence of postoperative AKI. The use of chloride liberal IVF was associated with hyperchloremic metabolic acidosis.

A prospective observational study of the use of desflurane anesthesia in Indian adult inpatients undergoing surgery: The Registry in India on Suprane Emergence registry.

BACKGROUND AND AIMS: Limited registry studies are available on the use of anesthetic agents. This registry was conducted to evaluate emergence outcomes in Indian adult patients undergoing surgery with desflurane anesthesia. MATERIAL AND METHODS: This multicenter, prospective, non-interventional, observational study (Registry in India on Suprane Emergence [RISE] registry) included adult inpatients who received desflurane as general anesthetic for surgical procedure of ≥2 h. Patients were stratified by age into three groups: ≥18-40 years, ≥41-65 years, and >65 years. Data on patients' demographics, practice, and usage pattern of medications were collected. The primary efficacy outcomes were time to extubation, time to response to verbal command, and time to orientation. RESULTS: Of 236 patients screened, 201 (≥18-40 years, n = 70; ≥41-65 years, n = 65; >65 years, n = 66) were enrolled in the study. Mean time to extubation observed in ≥18-40 years group was 7.2 ± 4.1 min, ≥41-65 years was 11.6 ± 8.99 min, and >65 years was 12.0 ± 10.5 min. Mean time to response to verbal command was 7.4 ± 4.3 min for ≥18-40 years, 10.9 ± 8.5 min for ≥41-65 years, and 10.0 ± 5.4 min for >65 years. Mean time to orientation was 13.0 ± 7.0 min for ≥18-40 years, 16.1 ± 12.0 min for ≥41-65 years, and 17.0 ± 8.6 min for >65 years. Incidence of nausea and retching/vomiting was observed in 8% of patients each in the postoperative period, and these complications were seen more in the >65 years age group. Overall, desflurane treatment maintained hemodynamic stability and no major airway events were reported. CONCLUSIONS: The RISE registry data suggest that desflurane-based anesthesia provides early recovery with stable hemodynamics without any airway adverse events, in a wide variety of surgical procedures.

Breast cancer recurrence after reoperation for surgical bleeding.

BACKGROUND: Bleeding activates platelets that can bind tumour cells, potentially promoting metastatic growth in patients with cancer. This study investigated whether reoperation for postoperative bleeding is associated with breast cancer recurrence. METHODS: Using the Danish Breast Cancer Group database and the Danish National Patient Register (DNPR), a cohort of women with incident stage I-III breast cancer, who underwent breast-conserving surgery or mastectomy during 1996-2008 was identified. Information on reoperation for bleeding within 14 days of the primary surgery was retrieved from the DNPR. Follow-up began 14 days after primary surgery and continued until breast cancer recurrence, death, emigration, 10 years of follow-up, or 1 January 2013. Incidence rates of breast cancer recurrence were calculated and Cox regression models were used to quantify the association between reoperation and recurrence, adjusting for potential confounders. Crude and adjusted hazard ratios according to site of recurrence were calculated. RESULTS: Among 30 711 patients (205 926 person-years of follow-up), 767 patients had at least one reoperation within 14 days of primary surgery, and 4769 patients developed breast cancer recurrence. Median follow-up was 7·0 years. The incidence of recurrence was 24·0 (95 per cent c.i. 20·2 to 28·6) per 1000 person-years for reoperated patients and 23·1 (22·5 to 23·8) per 1000 person-years for non-reoperated patients. The overall adjusted hazard ratio was 1·06 (95 per cent c.i. 0·89 to 1·26). The estimates did not vary by site of breast cancer recurrence. CONCLUSION: In this large cohort study, there was no evidence of an association between reoperation for bleeding and breast cancer recurrence.

Do pre-diagnosis primary care consultation patterns explain deprivation-specific differences in net survival among women with breast cancer? An examination of individually-linked data from the UK West Midlands cancer registry, national screening programme and Clinical Practice Research Datalink.

BACKGROUND: In England and Wales breast cancer survival is higher among more affluent women. Our aim was to investigate the potential of pre-diagnostic factors for explaining deprivation-related differences in survival. METHODS: Individually-linked data from women aged 50-70 in the West Midlands region of England, diagnosed with breast cancer 1989-2006 and continuously eligible for screening, was retrieved from the cancer registry, screening service and Clinical Practice Research Datalink. Follow-up was to the end of July 2012. Deprivation was measured at small area level, based on the quintiles of the income domain of the English indices of deprivation. Consultation rates per woman per week, time from last breast-related GP consultation to diagnosis, and from diagnosis to first surgery were calculated. We estimated net survival using the non-parametric Pohar-Perme estimator. RESULTS: The rate of primary care consultations was similar during the 18 months prior to diagnosis in each deprivation group for breast and non-breast symptoms. Survival was lower for more deprived women from 4 years after diagnosis. Lower net survival was associated with more advanced extent of disease and being non-screen-detected. There was a persistent trend of lower net survival for more deprived women, irrespective of the woman's obesity, alcohol, smoking or comorbidity status. There was no significant variation in time from last breast symptom to diagnosis by deprivation. However, women in more deprived categories experienced significantly longer periods between cancer diagnosis and first surgery (mean = 21.5 vs. 28.4 days, p = 0.03). Those whose surgery occurred more than 12 weeks following their cancer diagnosis had substantially lower net survival. CONCLUSIONS: Our data suggest that although more deprived women with breast cancer display lifestyle factors associated with poorer outcomes, their consultation frequency, comorbidities and the breast cancer symptoms they present with are similar. We found weak evidence of extended times to surgical treatment among most deprived women who were not screen-detected but who presented with symptoms in primary care, which suggests that treatment delay may play a role. Further investigation of interrelationships between these variables within a larger dataset is warranted.

Statin use and the risk of herpes zoster: a nested case-control study using primary care data from the U.K. Clinical Research Practice Datalink.

BACKGROUND: Statins are commonly prescribed worldwide and recent evidence suggests that they may increase the risk of herpes zoster (HZ). OBJECTIVES: To quantify the effect of statin exposure on the risk of HZ in the U.K. METHODS: A matched case-control study was conducted using data from U.K. primary care and hospital records. Patients > 18 years with an incident diagnosis of HZ were matched to up to four controls for age, sex and general practice. Patients were included in the statin exposure group if they had ever used a statin, and the daily dosage of the most recent statin prescription and the time since the most recent statin prescription were also recorded. The primary outcome was an incident diagnosis of HZ. Odds ratios (ORs) were estimated from conditional logistic regression and adjusted for potential confounders. RESULTS: A total of 144 959 incident cases of HZ were matched to 549 336 controls. Adjusted analysis suggested strong evidence for an increase in the risk of HZ related to statin exposure (OR 1·13, 95% confidence interval 1·11-1·15). There was also an increased risk when dosages were increased for patients who were currently or had recently been receiving statin treatment (Ptrend < 0·001), and we found an attenuation of the increased risk of HZ in previous statin users as the time since last statin exposure increased (Ptrend < 0·001). CONCLUSIONS: These findings are consistent with the hypothesis that statin therapy leads to an increase in the risk of HZ.

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom.

BACKGROUND/OBJECTIVES: The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the 'real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom. SUBJECTS/METHODS: A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed. RESULTS: Patients prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34-1.32). CONCLUSIONS: Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records.

OBJECTIVES: To investigate whether the use and timing of prescription of ß blockers in patients with chronic obstructive pulmonary disease (COPD) having a first myocardial infarction was associated with survival and to identify factors related to their use. DESIGN: Population based cohort study in England. SETTING: UK national registry of myocardial infarction (Myocardial Ischaemia National Audit Project (MINAP)) linked to the General Practice Research Database (GPRD), 2003-11. PARTICIPANTS: Patients with COPD with a first myocardial infarction in 1 January 2003 to 31 December 2008 as recorded in MINAP, who had no previous evidence of myocardial infarction in their GPRD or MINAP record. Data were provided by the Cardiovascular Disease Research using Linked Bespoke studies and Electronic Health Records (CALIBER) group at University College London. MAIN OUTCOME MEASURE: Cox proportional hazards ratio for mortality after myocardial infarction in patients with COPD in those prescribed ß blockers or not, corrected for covariates including age, sex, smoking status, drugs, comorbidities, type of myocardial infarction, and severity of infarct. RESULTS: Among 1063 patients with COPD, treatment with ß blockers started during the hospital admission for myocardial infarction was associated with substantial survival benefits (fully adjusted hazard ratio 0.50, 95% confidence interval 0.36 to 0.69; P<0.001; median follow-up time 2.9 years). Patients already taking a ß blocker before their myocardial infarction also had a survival benefit (0.59, 0.44 to 0.79; P<0.001). Similar results were obtained with propensity scores as an alternative method to adjust for differences between those prescribed and not prescribed ß blockers. With follow-up started from date of discharge from hospital, the effect size was slightly attenuated but there was a similar protective effect of treatment with ß blockers started during hospital admission for myocardial infarction (0.64, 0.44 to 0.94; P=0.02). CONCLUSIONS: The use of ß blockers started either at the time of hospital admission for myocardial infarction or before a myocardial infarction is associated with improved survival after myocardial infarction in patients with COPD. REGISTRATION: NCT01335672.

Validation of the Scale for the Assessment of Illness Behavior (SAIB) in a community sample of elderly people.

The aim of this study was to evaluate the construct validity of the SAIB in a community sample of elderly people. The SAIB was administered to a large community sample representative of the German population aged 60-85 years (n=1593). The original model was assessed and then refined through confirmatory and exploratory factor analyses. Criterion validity was evaluated by comparing SAIB scores with external criteria in 3 categories: subjective health, chronic illness and health care utilization. The originally suggested five factor structure of the SAIB yielded a comparative fit index (CFI) of 0.70 and the weighted root mean square residual (WRMR) was 3.68. A shortened questionnaire with 13 items and four factors resulted in better model fit (CFI 0.97 and WRMR 1.3). Correlations between subjective health and the new scales ranged from 0.06 to 0.33. Effect sizes (Cohens d) of mean differences in factor scores between those with and without healthcare system contact varied by healthcare type, ranging from 0.05 to 0.94; effect sizes were largest in relation to contact with psychotherapy and alternative medicine practitioners. We propose a shortened version of the SAIB with a different scale structure, which resulted in better model fit with our data. Neither the original nor revised SAIB appeared to discriminate well in terms of health care use, suggesting that the illness behavior as currently conceptualized may not fully explain the increased use of healthcare in the elderly.

Effects of air pollution on the incidence of myocardial infarction.

CONTEXT: Short-term fluctuations in air pollution have been associated with changes in both overall and cardiovascular mortality. OBJECTIVE: To consider the effects of air pollution on myocardial infarction (MI) risk by systematically reviewing studies looking at this specific outcome. DATA SOURCES: Medline, Embase and TOXNET publication databases, as well as reference lists and the websites of relevant public organisations. STUDY SELECTION: Studies presenting original data with MI as a specific outcome and one or more of the following as an exposure of interest were included: particulate matter (PM), black carbon/black smoke, ozone, carbon monoxide, nitrogen oxides, sulphur dioxide and traffic exposure. DATA EXTRACTION: The effects of each pollutant on risk of MI, including effect sizes and confidence intervals, were recorded where possible. Methodological details were also extracted including study population, location and setting, ascertainment of MI events, adjustment for potential confounders and consideration of lagged effects. RESULTS: 26 studies were identified: 19 looked at the short-term effects of pollution on a daily timescale; the remaining 7 at longer-term effects. A proportion of studies reported statistically significant detrimental effects of PM with diameter <2.5 microm (3/5 studies, risk increase estimates ranging from 5 to 17% per 10 microg/m(3) increase), PM <10 microm (3/10, 0.7-11% per 10 microg/m(3)), CO (6/14, 2-4% per ppm), SO(2) (6/13, effect estimates on varied scales) and NO(2 )(6/13, 1-9% per 10 ppb). Increasing ozone levels were associated with a reduction in MI risk in 3/12 studies. A number of differences in location, population and demographics and study methodology between studies were identified that might have affected results. CONCLUSION: There is some evidence that short-term fluctuations in air pollution affect the risk of MI. However, further studies are needed to clarify the nature of these effects and identify vulnerable populations and individuals.

Effects of ambient temperature on the incidence of myocardial infarction.

CONTEXT: While the effects of weather and, in particular, ambient temperature on overall mortality are well documented, the strength of the evidence base for the effects on acute myocardial infarction (MI) are less clear. OBJECTIVE: To systematically review studies specifically focusing on the effects of temperature on MI. DATA SOURCES: Medline, Embase, and GeoBase publication databases, as well as reference lists, and the websites of a number of relevant public organisations. STUDY SELECTION: Studies of original data in which ambient temperature was an exposure of interest and MI a specific outcome were selected. DATA EXTRACTION: The reported effects of ambient temperature on the risk of MI, including effect sizes and confidence intervals, where possible, were recorded. Methodological details were also extracted, including study population, location and setting, ascertainment of MI events, adjustment for potential confounders and consideration of lagged effects. RESULTS: 19 studies were identified, of which 14 considered the short-term effects of temperature on a daily timescale, the remainder looking at longer-term effects. Overall, 8 of the 12 studies which included relevant data from the winter season reported a statistically significant short-term increased risk of MI at lower temperatures, while increases in risk at higher temperatures were reported in 7 of the 13 studies with relevant data. A number of differences were identified between studies in the population included demographics, location, local climate, study design and statistical methodology. CONCLUSION: A number of studies, including some that were large and relatively well controlled, suggested that both hot and cold weather had detrimental effects on the short-term risk of MI. However, further research with consistent methodology is needed to clarify the magnitude of these effects and to show which populations and individuals are vulnerable.

Meditation from a mental health prospective.

The term "Meditation" is defined and the aims of meditation-practice are outlined. The physiological and psychological correlates of meditation, as found in different studies, are described. The need for an integrated approach to the study of consciousness is emphasized. The clinical applications of meditation practice are spelt out. Areas of further research are indicated.

Quadrivalvular rheumatic heart disease.

Three cases of chronic rheumatic heart disease with involvement of all four valves are presented. The involvement of tricuspid and pulmonary valves was suspected clinically and was confirmed by two-dimensional echo, Doppler, hemodynamic and angiographic findings. These findings were also verified surgically and histopathologically in 2 cases. One of the cases died after cardiac catheterization; the other 2 cases were treated surgically with success.