A theoretical approach to choosing the minimum number of multiple tumors required for assessing treatment response

BACKGROUND AND OBJECTIVE: Most advanced cancer patients have multiple tumors. Because the multiple tumors are from the same patient, the tumor sizes are expected to be correlated and the information contained in each additional tumor might not always have significant 'added value' toward the response assessment. Needing to measure only a subset of tumors would reduce workload for the study radiologist but is expected to increase the variability in response outcome. We compute this increment in variability and find a procedure for choosing the minimum number (m) of tumors among some fixed maximum number (M) of correlated tumors that must be considered to ensure precision of at least as high as a specified proportion of the precision obtained if one were to measure all M tumors. METHOD: The ratio V(m)(R)/V(M)(R) = M2[m + (m2 - m)rho(ICC)]/m2[M + (M2 - M)rho(ICC)] quantifies the percentage increment in variance of the response R, where rho(ICC) is the intra-class between tumors within patient correlation coefficient. The procedure for choosing the minimum number of tumors is demonstrated using data for 42 cancer patients with 10 or more tumors. RESULTS: Using the criterion that >20% increase in variability due to selection of a subset out of M of 10 tumors is unacceptable, we find that m of 9, 6, 5, 3, and 2 tumors are needed when rho(ICC)=0.0 (no correlation), 0.2, 0.4, 0.6, and 0.8, respectively. If the criterion is made stricter to >10%, the number of tumors needed rise to 10, 8, 6, 4, and 3, respectively. For the example, 6 tumors out of 10 are found to provide sufficiently stable response categorization confirming the theoretical result. CONCLUSION: If cancer research community can agree on a percentage of variability in response outcome that is unacceptable, it is mathematically possible to recommend a minimum number of tumors that should be used for response assessment.     

The impact of 'statutory duties' on mental health social workers in the UK

In the UK, applications for involuntary admission to psychiatric units are made mainly by specially trained approved social workers (ASWs). Proposed changes in the legislation will permit other professionals to undertake these statutory duties. This study aimed to examine how ASW status impacts upon work pattern and workload stresses by comparing ASWs with other mental health social workers who did not carry statutory responsibilities. A multimethod design was adopted that included a cross-sectional national survey of mental health social workers (n=237, including 162 ASWs), and a telephone survey of mental health service managers (n=60). Data were collected using a semistructured questionnaire and diary, the content of which was derived from focus-group work and standard measures. Features of job content, working patterns and conditions were described and their association with stress, burnout and job satisfaction examined. ASWs were older and had been qualified longer than non-ASWs. The working patterns and conditions of the two groups did not differ, although ASWs did more hours on duty. ASWs received less support at work, particularly from supervisors and their role afforded less decision latitude than that of non-ASWs. ASW status was related to an elevated GHQ score, particularly among males. Emotional exhaustion was very high (over two-thirds in both groups) but ASWs and non-ASWs did not differ in this or any other feature of burnout, only 8% of the sample were actually 'burnt-out', being more common among ASWs. ASWs were more dissatisfied and were more likely than non-ASWs to want to leave their job. Given that ASW status increased stress and job dissatisfaction, especially for men, and was related to a desire to leave one's current job, it seems likely that extending statutory duties to other professionals will increase levels of stress, burnout and dissatisfaction in these groups also. In turn, this might have consequences for staff recruitment and retention.     

Naloxone distribution and cardiopulmonary resuscitation training for injection drug users to prevent heroin overdose death: A pilot intervention study

Fatal heroin overdose has become a leading cause of death among injection drug users (IDUs). Several recent feasibility studies have concluded that naloxone distribution programs for heroin injectors should be implemented to decrease heroin overdose deaths, but there have been no prospective trials of such programs in North America. This pilot study was undertaken to investigate the safety and feasibility of training injection drug using partners to perform cardiopulmonary resuscitation (CPR) and administer naloxone in the event of heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection partners) were recruited from street settings in San Francisco. Participants took part in 8-hour training in heroin overdose prevention, CPR, and the use of naloxone. Following the intervention, participants were prospectively followed for 6 months to determine the number and outcomes of witnessed heroin overdoses, outcomes of participant interventions, and changes in participants’ knowledge of overdose and drug use behavior. Study participants witnessed 20 heroin overdose events during 6 months follow-up. They performed CPR in 16 (80%) events, administered naloxone in 15 (75%) and did one or the other in 19 (95%). All overdose victims survived. Knowledge about heroin overdose management increased, whereas heroin use decreased. IDUs can be trained to respond to heroin overdose emergencies by performing CPR and administering naloxone. Future research is needed to evaluate the effectiveness of this peer intervention to prevent fatal heroin overdose.     

Sternal wound dehiscence after internal mammary artery harvesting. Logical management. Part 2

Wound breakdown is a serious complication of median sternotomy. This is generally met with a further attempt at surgical apposition using sutures of monofilament surgical steel, following wound debridement. This often fails. The aim of this article is to demonstrate one surgeon's experience in his revised management of sternal wound dehiscence, following internal mammary artery (IMA) harvest, over a 7-year period. Treatment consisted of sternal and soft tissue debridement, and closed irrigation. Wound closure was performed using multiple interrupted deep tension sutures (DTS) only. We believe this article demonstrates that the use of DTS is a safe and effective method of closure, for patients suffering from sternal wound dehiscence following IMA harvest.     

High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart

Particular intestinal bacteria are capable of metabolizing the soya isoflavone daidzein to equol and/or O-desmethylangolensin (O-DMA), and the presence of these metabolites in urine after soya consumption are markers of particular intestinal bacteria profiles. Prevalences of equol producers and O-DMA producers are approximately 30-50 % and 80-90 %, respectively, and limited observations have suggested that these daidzein-metabolizing phenotypes are stable within individuals over time. Characterizing stability of these phenotypes is important to understand their potential as markers of long-term exposure to particular intestinal bacteria and their associations with disease risk. We evaluated concordance within an individual for the equol-producer and O-DMA-producer phenotypes measured at two time points (T1, T2), 1-3 years apart. Phenotypes were ascertained by analysing equol and O-DMA using GC-MS in a spot urine sample collected after 3 d soya (source of daidzein) supplementation. In ninety-two individuals without recent (within 3 months before phenotyping) or current antibiotics use, 41 % were equol producers at T1 and 45 % were equol producers at T2, and 90 % were O-DMA producers at T1 and 95 % were O-DMA producers at T2. The percentage agreement for the equol-producer phenotype was 82 and for the O-DMA-producer phenotype was 89. These results indicate that these phenotypes are stable in most individuals over time, suggesting that they provide a useful biomarker for evaluating disease risk associated with harbouring particular intestinal bacteria responsible for, or associated with, the metabolism of the soya isoflavone daidzein.     

A comparison of median effective doses of intrathecal levobupivacaine and ropivacaine for labor analgesia

BACKGROUND: The study was designed to determine and compare the median effective doses (MEDs) of intrathecal ropivacaine with levobupivacaine for labor analgesia. METHODS: In this double-blind study, 100 parturients in early labor were randomized to receive either intrathecal ropivacaine or levobupivacaine. For each drug, the patients were assigned to receive one of the five doses studied, namely 1, 1.5, 2, 2.5, or 3 mg. Effective analgesia was defined as a pain score (0-100 visual analog scale) of less than 10 within 15 min of injection, lasting for 45 min or more after the induction of analgesia. MEDs were derived from probit analysis. The duration of analgesia rendered by the two drugs at 2.5 and 3 mg was also compared. RESULTS: The MED for levobupivacaine was 1.07 mg (95% confidence interval, 0.88-1.25 mg), and the MED for ropivacaine was 1.40 mg (95% confidence interval, 1.20-1.61 mg). Levobupivacaine was found to be 1.31 (95% confidence interval, 1.04-2.01) times more potent than ropivacaine. At doses of 2.5 mg or greater, there was no significant difference in duration of analgesia between levobupivacaine (median, 63.5 min; range, 46-123 min) and ropivacaine (median, 59.0 min; range, 47-93 min; P = 0.18). We detected no difference in the incidence of hypotension, nausea and vomiting, motor block, or abnormal fetal heart tracing between the two drugs. CONCLUSIONS: The MED of intrathecal ropivacaine for labor analgesia was significantly greater than levobupivacaine experimentally, but this significance was reduced when the comparison was based on molar potency. There was no difference in the duration of analgesia or adverse effects between the two drugs at higher doses (2.5 mg or greater).     

Node-positive transcranial recurrent melanoma: is an aggressive resection warranted?

Locally advanced, node-positive recurrence of malignant melanoma is a harbinger of distant metastases and signifies poor prognosis. However, the clinical course may vary due to the unpredictable biology of malignant melanoma. The presented patient developed a recurrent melanoma of the scalp that eroded through the skull and involved regional lymph nodes with extracapsular extension. He was treated with wide local excision of the recurrence, bilateral posterolateral neck dissection, and immediate microvascular reconstruction followed by adjuvant radiation therapy. The patient remains free of disease at 12 years. This case illustrates that an aggressive resection should be considered for the operable patients with locally advanced recurrent melanoma to render them disease free surgically.