Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

What is the difference between squamous cell carcinoma and adenocarcinoma of the cervix? A matched case–control study

The objective of this study was to investigate the efficacy of treatment strategies in patients with adenocarcinoma (AC) of the cervix and compare it with those with squamous cell carcinoma (SCC) of the cervix. Women with FIGO (1994) stage IB1 AC, especially pathologic tumor size of 2-4 cm, treated with class III hysterectomy, were compared with those with SCC treated with comparable strategy in a case-controlled study. Eighty patients (20 cases, 60 controls) were analyzed. Lymphvascular space invasion (P = 0.01) and lymph node metastasis (P = 0.07) were more frequent in patients with SCC than in those with AC. However, there was no significant difference in depth of stromal invasion (P = 0.51) and invasion of the parametrium (P = 0.44) between two groups. And there was also no statistically significant difference in disease-free survival (P = 0.86) and overall survival (P = 0.89) between two groups. Primary radical surgery followed by adjuvant therapy, same as for SCC, would be acceptable for AC with pathologic tumor size of 2-4 cm. Although it was difficult to determine whether AC recurred more systemically, more effective treatment strategies than those currently available for AC should be considered to reduce the systemic recurrence.     

Tear of the distal biceps branchii tendon: A new method of ultrasound evaluation

Tear of the distal biceps brachii tendon is an uncommon injury. Ultrasound evaluation of the distal tendon using an anterior approach is often difficult because of technical factors. We describe a new method of ultrasound evaluation of the distal biceps tendon insertion. This involves a posterior approach with the forearm pronated. With pronation of the forearm, the radial tuberosity faces posteriorly, bringing the distal biceps tendon insertion into view. A surgically proven case of distal biceps tendon tear is presented to illustrate our technique.     

Achilles tendinopathy after treatment with fluoroquinolone

Fluoroquinolone antibiotic therapy is a recognized but poorly understood cause for Achilles tendinopathy. We report here a patient who developed bilateral partial Achilles tendon tears as a result of fluoroquinolone therapy. Ultrasound and MRI were both useful in identifying and distinguishing between Achilles tendinosis and tendon rupture. The current published literature on this problem was also reviewed.     

Physician‐related facilitators and barriers to patient involvement in treatment decision making in early stage breast cancer: perspectives of physicians and patients

Objective To identify patients’ and physicians’ perceptions of physician‐related verbal and nonverbal facilitators and barriers to patient involvement in treatment decision making (TDM) occurring during clinical encounters for women with early stage breast cancer (ESBC). Methods Eligible women were offered treatment options including surgery and adjuvant therapy. Eligible physicians provided care for women with ESBC in either a teaching hospital or an academic cancer centre. In Phase 1, women were interviewed 1–2 weeks after their initial consultation. In Phase 2, women and their physicians were interviewed separately while watching their own consultation on a digital video disk. All interviews were audiotaped, transcribed and analysed. Results Forty women with ESBC and six physicians participated. Patients and physicians identified thirteen categories of physician facilitators of women’s involvement. Of these, seven categories were frequently identified by women: conveyed a rationale for patient involvement in TDM; explained the risk of cancer recurrence; explained treatment options; enhanced patient understanding of information; gave time for TDM; offered a treatment recommendation; and made women feel comfortable. Physicians described similar information‐giving facilitators but less often mentioned other facilitators. Few physician barriers to women’s involvement in TDM were identified. Conclusions Women with ESBC and cancer physicians shared some views of how physicians involve patients in TDM, although there were important differences. Physicians may underestimate the importance that women’s place on understanding the rationale for their involvement in TDM and on feeling comfortable during the consultation.     

Endogenous protein phosphorylation by resting and activated human neutrophils

NADPH oxidase is an enzyme in the plasma membrane of the neutrophil that catalyzes the production of O2-, a species central to the oxygen- dependent killing mechanisms of this cell. The oxidase is dormant in resting cells and is activated upon the addition of a stimulus. Neutrophils of patients with chronic granulomatous disease (CGD) manifest no oxidase activity when stimulated. The possible role of protein phosphorylation in the activation of NADPH oxidase was examined in normal and CGD neutrophils by measuring the incorporation of 32Pi into proteins as determined by gel electrophoresis followed by autoradiography. Resting neutrophils from normal subjects exhibit at least 40 distinct phosphoprotein bands. The level of phosphorylation of these bands was examined after the addition of phorbol myristate acetate (PMA), opsonized zymosan, digitonin, N-formyl-methionyl- phenylalanine (FMLP), or NaF. PMA and opsonized zymosan increased the phosphorylation of a set of 6 protein bands. Digitonin and FMLP consistently caused the phosphorylation of 4 of these protein bands, while NaF failed to induce increased phosphorylation of any protein band. All activators tested caused the dephosphorylation of one specific protein band. The time course of phosphorylation (dephosphorylation) was examined using PMA as the activating agent. Increased phosphorylation of one protein band was evident by 12 sec after the addition of PMA. The most slowly phosphorylated protein band did not slow evidence of change until 5 min after the addition of PMA. Three of the phosphoproteins examined were phosphorylated either earlier than or concomitant with the activation of NADPH oxidase. CGD neutrophils were compared with normal cells for their ability to phosphorylate proteins in response to PMA. The phosphoprotein banding patterns of CGD neutrophils were identical with those of normal neutrophils in both the resting and activated states. The evidence presented shows that the phosphorylation of proteins is a prominent feature of neutrophil metabolism. The striking similarity of phosphorylation changes induced by the various activators tested suggests that protein phosphorylation may play a role in some aspects of neutrophil activation. Evidence was not obtained, however, regarding a link between protein phosphorylation and activation of NADPH oxidase.     

Beclomethasone dipropionate aerosol and oropharyngeal candidiasis.

In a survey of 400 consecutive patients with chronic asthma treated with beclomethasone dipropionate aerosol (up to 400 mug/day) the prevalence of oropharyngeal thrush was 4-5%. The prevalence of this complication was not significantly related to sex, age, duration of treatment with beclomethasone or concurrent treatment with prednisolone. Yeasts were isolated from throat swabs in about 60% of all patients and in 48% of normal controls. Thus, although a diagnosis of oropharyngeal thrush was recorded only when the presence of characteristic lesions in the pharynx was associated with a positive culture, there was a large number of patients and controls without thrush who harboured yeasts in the throat. One in 3 patients with thrush complained of sore throat or hoarseness, but 1 in 4 patients without thrush had similar symptoms. These findings suggest that, although treatment with beclomethasone dipoprionate aerosol undoubtedly can cause oropharyngeal thrush, this condition is not an inevitable result of colonization of the oropharynx by yeasts, nor is it necessarily associated with symptoms.     

Tricuspid annulus motion and mitral annulus motion: Anatomical intimacy causing a good correlation?

BACKGROUND:

Echocardiographic evaluation of the heart and its function, especially left ventricular systolic function, has great clinical importance. Systolic function can be measured using several methods, such as the amplitude of motion of the left atrioventricular plane (mitral annulus motion [MAM]) toward the apex during systole. Similarly, right ventricular systolic function can be measured using the motion of the right atrioventricular plane (tricuspid annulus motion [TAM]) toward the apex during systole.

OBJECTIVES:

Because the mitral and tricuspid annuli are situated close to each other in the fibrous skeleton between both ventricles and atria, one might think that a decrease in the amplitude of MAM would be followed by a decrease in the amplitude of TAM. The present study was developed to determinine if this anatomical intimacy causes a good correlation between the amplitudes of TAM and MAM.

METHODS:

Nineteen healthy subjects and 103 consecutive patients were included in the study and examined using echocardiography. The amplitudes of TAM and MAM were measured and the correlation between the amplitudes was calculated.

RESULTS:

In the 103 consecutive patients, a significant but relatively weak positive correlation was found between TAM and MAM amplitudes (Pearson’s correlation coefficient [r]=0.58; P<0.001). In the 19 healthy subjects, no significant correlation was found.

CONCLUSIONS:

Despite the anatomical intimacy of the annuli, the correlation between the amplitudes of TAM and MAM in consecutive patients was rather weak, and there was no correlation in healthy subjects. These findings could be due to anatomical and physiological differences between the right and left ventricles.     

Précising definitions as a way to combat overdiagnosis

Roughly, overdiagnosis (ODx) occurs when people are harmed by receiving diagnoses (often accompanied by interventions) that do not benefit them, usually because the diagnosed conditions do not pose a threat to their health. ODx is a theoretical as well as a practical problem as it relates to definitions of disease. Elsewhere, it has been argued that disease is a vague concept and that this vagueness may contribute to ODx. In response, we develop a stipulative or précising definition of disease, for the specific purpose of decreasing or preventing ODx. We call this disease_ODx, aimed at distinguishing cases where it would be beneficial to identify (and treat the condition) from those where diagnosis is more likely to harm than benefit. A preliminary definition of disease_ODx is that X is a disease_ODx iff there is dysfunction that has a significant risk of causing severe harm. This paper examines the 3 concepts in this definition, using a naturalistic account of function, a Feinbergian account of comparative harm, and a probabilistic understanding of risk. We then test the utility of this approach using examples of clinical conditions that are currently overdiagnosed.