Resident work hours and working environment in otolaryngology. Analysis of daily activity and resident perception

OBJECTIVE.--To analyze the working environment and work hours of a cohort of otolaryngology--head and neck surgery residents. DESIGN.--Environmental analysis questionnaire and a log of daily activities. SETTING.--Residents were on a clinical rotation system. PARTICIPANTS.--Fifty-nine residents from six programs, including three public and three private institutions, from geographically diverse regions of the country were involved in the study. Residents were equally distributed from their second year through their fifth year of postgraduate work. All eligible residents participated in and completed the study. INTERVENTION.--The environmental analysis survey was designed to elicit resident perception of different aspects of their working environment. The daily activity log required the resident to report on activities for each half-hour period for 7 consecutive days. RESULTS.--Residents were on call an average of 52.8 hours (2.2 days) and worked 79.4 hours per week. Seventy-five percent believed that the level of faculty supervision and the degree of resident responsibility was about right. Two major inefficiencies were the time involved in completion of paperwork and the lack of nonmedical support services. Thirty-one percent of the residents responded that fatigue resulted in substandard patient care 10% of the time. Forty-seven percent responded that their educational experience was substandard 25% of the time secondary to fatigue. Two thirds responded that the demands of residency training had a negative impact on their family and personal life. CONCLUSIONS.--Seventy percent of the otolaryngology--head and neck surgery residents surveyed at six institutions believe that an 80-hour workweek, including being on call every third night with no more than 24 hours of continuous work without sleep, approximates a reasonable, maximum work schedule. Residents working the longest hours expressed concern about rendering substandard care and developing negative attitudes toward patients. Noneducational inefficiencies were identified and solutions were proposed. Demands of residency training, even within guidelines established as reasonable, can have detrimental effects on residents' educational activities and personal life.     

Description and validation of a method for simultaneous estimation of effective population size and mutation rate from human population data

A method is presented for utilizing population data on electrophoretic variants of proteins to estimate simultaneously the effective sizes (Ne values) of the populations in question and the rate of mutation resulting in electromorphs at the loci whose products were surveyed. The method is applied to data from 12 relatively unacculturated Amerindian tribes for whom census data and independent estimates of the number of different electrophoretic variants at 27 loci are available. Because of tribal demographic structure, Ne should be less than the current number of reproductive-aged adults. In fact, it is substantially greater for 7 tribes, most likely due to intertribal migration and a recent decrease in tribal size. Estimates of locus mutation rates for the 27 loci vary by more than a factor of 20, with an average of 1.1 x 10(-5) per locus per generation. This latter estimate is in satisfactory agreement with the results of other indirect approaches to the estimation of mutation rates in these tribes but about two times higher than the results of direct estimates based on these same loci in studies on civilized populations. This discrepancy could be due to the above-hypothesized migration and to decreases in tribal size.     

Plasma lipids in juvenile chronic granulocytic leukaemia

Plasma lipid parameters (triglycerides, total cholesterol and high density lipoprotein cholesterol) were measured in 7 children with juvenile chronic granulocytic leukaemia, of whom 3 were with and 4 without xanthomas. In all cases, whatever the stage of the disease, these parameters were extremely altered. Plasma triglycerides were generally increased, total and HDL cholesterols were very low. No relationship seems to exist between these values and the occurrence of xanthomas.     

Migraineurs' perceptions of and interactions with pharmacists: a qualitative study

Aims and objectives Migraine is an underdiagnosed and undertreated condition. Diagnosed and undiagnosed migraineurs come into frequent contact with pharmacists, who are in a unique position to intervene and potentially improve the therapeutic outcomes of migraineurs; however, little is known about migraineurs' attitudes towards pharmacists' roles and the experiences they have shared with pharmacists. The purpose of this study was to evaluate migraineurs' perceptions of the roles that pharmacists may play in helping them manage their disease. Setting Duquesne University, Pittsburgh, Pennsylvania, USA. Method The study employed the use of two focus groups of migraineurs from a university population, approached from a phenomenologic perspective. Focus‐group sessions were conducted using a flexible interview guide. Focus‐group content was digitally recorded, then transcribed, verified for accuracy and content analysed according to established criteria, employing the use of a formal coding procedure. Inductive analysis was performed to establish patterns, themes and categories in the data. Key findings Six principal themes emerged. Among the most important findings were that (1) migraineurs were concerned about managing their headaches and the impact migraine has on their lives and their families' lives, (2) migraineurs did not discuss their headaches or migraine therapy with pharmacists and (3) migraineurs believe that many communication barriers exist in their pharmacistpatient relationship. Conclusion Community pharmacists have an opportunity to impact the level of care provided to migraine sufferers. As such, community pharmacists should strive to remove communication barriers and be more proactive during interactions with these patients. Further study may examine how pharmacists can elicit more social support for migraineurs and to help migraineurs cope with their condition.     

Anatomical evidence for the interaction of sympathetic and parasympathetic neurons in the cardiac ganglion of Necturus

Evidence of a direct interaction between sympathetic and parasympathetic elements in a cardiac parasympathetic ganglion is presented in this study. Experiments were done using acutely dissected or organ cultured parasympathetic cardiac ganglion preparations from Necturus maculosus (mudpuppy). The glyoxylic acid-induced fluorescence technique was used to visualize catecholamine-containing cells and fibers. Numerous long brightly fluorescent varicose fibers form a complex network over clusters of parasympathetic ganglion cells and strands of cardiac muscle. In addition to these fibers, there are numerous small brightly fluorescent interneurons (SIF cells) interspersed between individual parasympathetic ganglion cells. Long fibers and processes from the interneurons join to form bundles which arborize over groups of parasympathetic cells. In peripherally located smaller groups of ganglion cells there are no interneurons, but some of these parasympathetic cells appear to receive innervation from the long continuous fluorescent axons. Two experimental procedures were applied to support the conclusion that these long fibers were indeed sympathetic postganglionic axons: explants of cardiac ganglia were maintained for varying times to produce degeneration of any severed axons: chemical sympathectomy was produced by injection of 6-hydroxydopamine. The intrinsic SIF cells were apparently unaffected by both procedures. After 8 days in culture or after 6-OH dopamine treatment, all of the long continuous brightly fluorescent fibers, which normally intermingle with clusters of ganglion cells or innervate cardiac muscle, were absent. This indicates their extra-ganglionic origin. All of the isolated groups of parasympathetic ganglion cells not containing SIF cells were totally devoid of any catecholamine-containing fibers.     

The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia–reperfusion injury

Objective: Ischemia–reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H₂S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H₂S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.     

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

Ovarian cancer is the eighth most common cancer and cancer death in women worldwide (1). High-grade serous tubo-ovarian cancer (HGSC) constitutes ∼70% of all ovarian malignancies and has the worst prognosis (2). Current treatment of most patients with HGSC consists of cytoreductive surgery and combination chemotherapy with platinum-containing DNA–cross-linking drugs and taxane-based microtubule-stabilizing agents (2). Although treatment significantly improves survival, most women relapse with chemotherapy-refractory disease and eventually succumb (3). Multiple mechanisms of chemoresistance have been documented (4, 5), including reduced intracellular drug accumulation (6), detoxification by increased levels of glutathione (7), altered DNA damage repair (8, 9), dysfunctional apoptotic pathways (10, 11), and hyperactivation of various cell signaling pathways (12–14). These mechanistic studies are consistent with recent genomic analyses that reveal marked clonal evolution of HGSC during therapy (15). Other evidence, however, supports a hierarchical organization of HGSC, featuring intrinsically chemoresistant “cancer stem cells” (CSCs) that can escape initial treatment and seed recurrence (16–18).Although there is uniform agreement that HGSC patients should receive surgery and chemotherapy, the optimal order and timing of these modalities remain controversial. Two main options exist: primary debulking surgery with adjuvant chemotherapy (PDS), or neoadjuvant chemotherapy, followed by interval debulking surgery (NACT) (19–24). In either case, the surgical standard of care is to seek maximal cytoreduction, with the objective being to leave no visible residual disease. However, the precise definition of such “optimal debulking” can vary among different centers, surgeons, and reports (19, 21, 24, 25).Several studies have found similar outcomes after PDS or NACT, including two highly influential randomized trials (EORTC and CHORUS) carried out across multiple countries (22, 23, 26–28). In both trials, however, the question of potential bias in patient recruitment has been raised, favoring potentially those with more extensive disease, who are less likely benefit from “upfront” surgery (23, 28). Consistent with this interpretation, overall survival in these trials was significantly shorter than that seen in other HGSC cohorts (19, 24, 29, 30). Closer examination of these reports reveals additional factors that might have influenced their conclusions. The EORTC study had inconsistencies in optimal debulking rates between participating centers, with the PDS-associated complete debulking data highly influenced by the results from a single institution (23). The CHORUS study involved 76 clinical sites, and there were substantial differences in surgery execution and chemotherapy drug selection/dosage between them (28).At Princess Margaret Cancer Center, retrospective data showed that PDS patients with no visible disease postresection survived substantially longer (7-y survival, >60%) than those receiving NACT (7-y survival, ∼10%). Furthermore, although residual tumor postresection is a critical determinant of survival, its influence on the PDS group was far more dramatic than on NACT group (24). Of course, this report suffers from deficiencies common to all retrospective analyses, including lack of randomization to account for tumor burden at diagnosis and other factors; indeed, the NACT group in this study did have more extensive disease.Another controversy in HGSC management focuses on the potential benefit of earlier diagnosis. Earlier diagnosis of primary HGSC is generally assumed to enhance patient survival and quality of life (3). Intuitively, one might predict that the same reasoning would apply to recurrent disease; however, survival is similar in relapsed patients treated earlier, based on increasing serum CA125 levels, than in those treated only when physical symptoms of recurrence appear (31). Conceivably, the lead time between CA125 rise and clinical recurrence is too short for earlier chemotherapy to be beneficial; if so, then patient survival might be extended by more sensitive methods, such as testing for circulating tumor DNA (ctDNA) (32, 33).To address these issues, we developed a mathematical framework that models the dynamics of HGSC progression, response to surgery and chemotherapy, and recurrence. Our results, generated over a wide range of parameters and accounting for hierarchical and stochastic models of tumor initiation, argue that PDS is superior to NACT when complete debulking is feasible and suggest that, with currently available therapies, the benefits of earlier detection are intrinsically restricted to primary HGSC.     

Traumatic hemoperitoneum of splenopancreatic origin. Apropos of 155 cases. Can a non-surgical treatment be proposed?]

From 1985 to 1990, we treated 155 patients presenting with a hemoperitoneum secondary to a splenic or hepatic injury (diagnosis established by sonography, puncture and washout and/or laparotomy). These were 39 children and 116 young adults (average age 33 years). Fifty-eight of them (37%) suffered from multiple injuries (11 children, 47 adults). Splenic lesions were observed in 110 cases and hepatic lesions in 45. Ninety-one patients were operated, 55 in emergency and 36 later, while a watch-and-wait policy was applied to 64 (42%), with repeated clinical and complementary (ultrasound and/or CT) examinations. The indication for surgery was based on the clinical findings and the necessity of blood transfusion (more than 40 ml/kg/24 h in children, more than 2 to 5 U/24 h in adults, according to the context). This attitude allowed us to avoid operating two-thirds of the children and one third of the adults. We assess the limitations of this method.