Evaluating the effectiveness of organisational-level strategies with or without an activity tracker to reduce office workers' sitting time: a cluster-randomised trial.

BACKGROUND: Office workers engage in high levels of sitting time. Effective, context-specific, and scalable strategies are needed to support widespread sitting reduction. This study aimed to evaluate organisational-support strategies alone or in combination with an activity tracker to reduce sitting in office workers. METHODS: From one organisation, 153 desk-based office workers were cluster-randomised (by team) to organisational support only (e.g., manager support, emails; 'Group ORG', 9 teams, 87 participants), or organisational support plus LUMOback activity tracker ('Group ORG + Tracker', 9 teams, 66 participants). The waist-worn tracker provided real-time feedback and prompts on sitting and posture. ActivPAL3 monitors were used to ascertain primary outcomes (sitting time during work- and overall hours) and other activity outcomes: prolonged sitting time (≥30 min bouts), time between sitting bouts, standing time, stepping time, and number of steps. Health and work outcomes were assessed by questionnaire. Changes within each group (three- and 12 months) and differences between groups were analysed by linear mixed models. Missing data were multiply imputed. RESULTS: At baseline, participants (46 % women, 23-58 years) spent (mean ± SD) 74.3 ± 9.7 % of their workday sitting, 17.5 ± 8.3 % standing and 8.1 ± 2.7 % stepping. Significant (p < 0.05) reductions in sitting time (both work and overall) were observed within both groups, but only at 12 months. For secondary activity outcomes, Group ORG significantly improved in work prolonged sitting, time between sitting bouts and standing time, and overall prolonged sitting time (12 months), and in overall standing time (three- and 12 months); while Group ORG + Tracker, significantly improved in work prolonged sitting, standing, stepping and overall standing time (12 months). Adjusted for confounders, the only significant between-group differences were a greater stepping time and step count for Group ORG + Tracker relative to Group ORG (+20.6 min/16 h day, 95 % CI: 3.1, 38.1, p = 0.021; +846.5steps/16 h day, 95 % CI: 67.8, 1625.2, p = 0.033) at 12 months. Observed changes in health and work outcomes were small and not statistically significant. CONCLUSIONS: Organisational-support strategies with or without an activity tracker resulted in improvements in sitting, prolonged sitting and standing; adding a tracker enhanced stepping changes. Improvements were most evident at 12 months, suggesting the organisational-support strategies may have taken time to embed within the organisation. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry: ACTRN12614000252617 . Registered 10 March 2014.

Adherence to controller asthma medications: 6-month prevalence across a US community pharmacy chain.

WHAT IS KNOWN AND OBJECTIVE: Non-adherence to controller asthma medications is an important public health problem. It is estimated to occur in 30-70% of individuals and is a significant risk factor for asthma morbidity and mortality. The aim of this study was to determine the level of adherence, as indicated by refill rates, to controller asthma medications in a community pharmacy setting. METHODS: Secondary analyses of a community pharmacy dispensing database in 15 locations throughout Utah. RESULTS AND DISCUSSION: The dispensing records of 2193 patients who received controller medications for asthma in a 12-month period, and had a minimum of 6-month potential coverage (180 days) from the date of their first receipt of a controller medication in that period, were examined. Using standard metrics to gauge adherence, the proportion of days covered (PDC) and the medication possession ratio (MPR), the average coverage for controller asthma medications across a 6-month period (180 days) was poor, averaging less than 50% of days' availability. Standard cut-offs (≥80% medication availability) indicated that only 14-16% of patients had 'satisfactory' adherence over their 6-month follow-on period. Females and older patients had significantly greater satisfactory adherence. Medication adherence was significantly greater with inhaled corticosteroid (ICS)-long-acting ß2 -agonist (LABA) combinations than with ICS alone. WHAT IS NEW AND CONCLUSION: This study confirms the considerable scope of the asthma therapy non-adherence problem. Therefore, it is imperative to conduct survey-based research linked directly to pharmacy-based dispensing data to derive patient behavioural, attitudinal and environmental factors that may contribute to the issue, and then pilot and evaluate interventions for change.

The effect of fixed combination of fluticasone and salmeterol on asthma drug utilization, asthma drug cost, and episodes of asthma exacerbations.

OBJECTIVE: This study evaluated the use and drug costs of inhaled corticosteroids (ICSs), long-acting beta2-agonists (LABAs), and fluticasone propionate and salmeterol in a fixed-dose combination (FSC) and their relationship to asthma exacerbations before and after the market introduction of FSC in April 2001. METHODS: This is a retrospective analysis of employer-sponsored health insurance claims filed between January 1, 1998, and December 31, 2003 to detect impact of introduction of FSC (approved by the US Food and Drug Administration in August 2000) on utilization and cost of FSC, any ICS (excluding FSC), and any LABA (excluding FSC) along with utilization of medical services related to asthma exacerbations. Asthma medications were identified using National Drug Codes and Redbook, whereas asthma exacerbations were identified using ICD-9-CM primary diagnosis code 493.x. These medical and pharmacy claims were converted to rates per 100 asthma office visits. RESULTS: For all ICSs, the average pharmacy claims per 100 office visits increased from 383 in the year before FSC was introduced to 407 (120 [29.5%] were for FSC and 287 [70.5%] were for single-entity ICSs) in 2003. LABA prescribing increased from 72 in the year before FSC to 147 (120 from FSC, 27 single-entity LABA) in 2003 (p < 0.001). An additional $13,511 per 100 asthma office visits was spent on the FSC product (p < 0.001). After the introduction of FSC, there was no significant difference in asthma admissions (p = 0.17), whereas emergency department (ED) visits increased by 0.92 visits per 100 office visits (p = 0.03). The diagnosis and severity of asthma was inferred from the pharmacy claims and patients with chronic obstructive pulmonary disease could not be excluded. In addition, the study was not designed to assess the impact of other asthma medications on the disease and/or associated costs, and patient adherence to claimed medication could not be monitored. CONCLUSIONS: The introduction of FSC was associated with increased LABAs/FSC patient exposure and expenditure with no change in asthma hospitalizations and an increase in ED visits.

Investigation of an increase in postpartum haemorrhage in Canada.

OBJECTIVE: To investigate the cause of a recent increase in hysterectomies for postpartum haemorrhage in Canada. DESIGN: Retrospective cohort study. SETTING: Canada between 1991 and 2004. POPULATION: All hospital deliveries in Canada as documented in the database of the Canadian Institute for Health Information (excluding incomplete data from Quebec, Manitoba and Nova Scotia). METHODS: Deliveries with postpartum haemorrhage by subtype were identified using International Classification of Diseases codes, while hysterectomies were identified using procedure codes. Changes in determinants of postpartum haemorrhage (all postpartum haemorrhage and that requiring hysterectomy) were examined, and crude and adjusted period changes were assessed using logistic models. MAIN OUTCOME MEASURES: Postpartum haemorrhage, postpartum haemorrhage with hysterectomy, postpartum haemorrhage with blood transfusion and postpartum haemorrhage by subtype. RESULTS: Rates of postpartum haemorrhage increased from 4.1% in 1991 to 5.1% in 2004 (23% increase, 95% CI 20-26%), while rates of postpartum haemorrhage with hysterectomy increased from 24.0 in 1991 to 41.7 per 100,000 deliveries in 2004 (73% increase, 95% CI 27-137%). These increases were because of an increase in atonic postpartum haemorrhage, from 29.4 per 1000 deliveries in 1991 to 39.5 per 1000 deliveries in 2004 (34% increase, 95% CI 31-38%). Adjustment for temporal changes in risk factors did not explain the increase in atonic postpartum haemorrhage but attenuated the increase in atonic postpartum haemorrhage with hysterectomy. CONCLUSIONS: There has been a recent, unexplained increase in the frequency, and possibly the severity, of atonic postpartum haemorrhage in Canada.

Misoprostol versus oxytocin for the reduction of postpartum blood loss.

OBJECTIVE: To compare the effect of 400 mug of oral misoprostol with 5 U of intravenous oxytocin in the reduction of postpartum blood loss and prevention of postpartum hemorrhage. METHODS: In a prospective, double-blind, randomized controlled trial conducted in a tertiary maternity hospital 622 women received either 400 mug of oral misoprostol or 5 U of intravenous oxytocin after delivery of the anterior shoulder or within 1 min of delivery. The primary outcome was a hematocrit drop of 10% or greater 24 h postpartum. The secondary outcomes were a hemoglobin drop of 30 mg/L or greater, the use of additional oxytocin, an estimated blood loss greater than 1000 mL, manual removal of the placenta, a blood transfusion, and shivering and fever (>or=38 degrees C) as adverse effects of misoprostol. RESULTS: There was no difference between the 2 groups regarding the primary outcome (a >or=10% hematocrit drop occurred in 3.4% and 3.7% of the participants in the oxytocin and misoprostol groups, P=0.98). The rate of use of additional oxytocin was higher in the misoprostol group (51% versus 40.5%, P=0.01). Shivering was confined to the misoprostol group (6.8%), and fever occurred in 12.5% of the women in the misoprostol group and 0.3% of the women in the oxytocin group. CONCLUSION: The routine use of 400 microg of oral misoprostol was no less effective than 5 U of intravenous oxytocin in reducing blood loss after delivery, as assessed by change in postpartum hematocrit. The adverse effects of misoprostol were mild and self-limiting.

Misoprostol compared with prostaglandin E2 for labour induction in women at term with intact membranes and unfavourable cervix: a systematic review.

BACKGROUND: Misoprostol is a commonly used prostaglandin to induce labour. A potential risk of induction, however, is caesarean delivery, especially in women with an unfavourable cervix. OBJECTIVES: To evaluate the use of misoprostol, compared with prostaglandin E2 (PgE2), for labour induction in women at term with an unfavourable cervix and intact membranes. SEARCH STRATEGY: PubMed, Medline, EMBASE and the Cochrane Library were searched for articles published in any language from January 1987 to December 2005, using the keywords 'misoprostol', 'labour/labor' and 'induction'. SELECTION CRITERIA: We identified randomised trials of women at term (> or =37 weeks of gestation) with intact membranes and unfavourable cervix, undergoing labour induction with misoprostol, orally, vaginally, sublingually or buccally, compared with PgE2 vaginally or intracervically. DATA COLLECTION AND ANALYSIS: Caesarean delivery was the primary outcome, with tachysystole and hyperstimulation as secondary outcomes. The primary analysis compared any misoprostol with any PgE2 for all women, with a subgroup analysis for nulliparous women. Secondary analyses compared different routes and doses of misoprostol (oral or vaginal and 25 microgram or >25 microgram) and PgE2 (intracervical or vaginal). Relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. Main results Fourteen of 611 articles identified met the criteria for systematic review, with three providing information for nulliparous women. There was no difference in the risk of caesarean delivery between misoprostol and PgE2 groups (RR = 0.99, 95% CI = 0.83-1.17). Any misoprostol was associated with higher risks of tachysystole and hyperstimulation compared with any PgE2 (RR = 1.86, 95% CI = 1.01-3.43 and RR = 3.71, 95% CI = 2.00-6.88, respectively). There was a higher rate of vaginal delivery within 24 hours among all vaginal deliveries with any misoprostol compared with any PgE2 (RR = 1.14, 95% CI = 1.00-1.31), and among all deliveries, a lower rate of oxytocin use (RR = 0.71, 95% CI = 0.60-0.85) but a trend towards increased meconium staining was observed (RR = 1.22, 95% CI = 0.96-1.55). The use of misoprostol at starting dosages >25 microgram had similar findings to the primary analysis. Studies of lower misoprostol dosing (starting dose of 25 microgram) did not show any differences in the outcomes of interest, but the sample size of this secondary analysis was small (304 women, 155 receiving misoprostol). AUTHOR'S CONCLUSIONS: Although misoprostol in women at term with an unfavourable cervix and intact membranes was more effective than PgE2 in achieving vaginal delivery within 24 hours, misoprostol does not reduce the rate of caesarean delivery either in all women or in the subgroup of nulliparous women, and it increases the rates of tachysystole and hyperstimulation. Further studies of misoprostol using a starting dose of 25 microgram may be warranted.

Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism.

Alemtuzumab is a humanized IgG1 kappa antibody directed against CD52, a glycosyl-phosphatidylinositol linked cell-membrane protein of unknown function. Herein, we demonstrate that alemtuzumab promotes rapid death of chronic lymphocytic leukemia (CLL) cells in vitro, in a complement and accessory cell free system. Using minimal detergent solubilization of CLL membranes, we found that CD52 colocalizes with ganglioside GM-1, a marker of membrane rafts. Fluorescence microscopy revealed that upon crosslinking CD52 with alemtuzumab+anti-Fc IgG, large patches, and in many cases caps, enriched in CD52 and GM-1 formed upon the CLL cell plasma membrane. Depletion of membrane cholesterol or inhibition of actin polymerization significantly diminished the formation of alemtuzumab-induced caps and reduced alemtuzumab-mediated CLL cell death. We compared alemtuzumab-induced direct cytotoxicity, effector cell-mediated toxicity and complement-mediated cytotoxicity of CLL cells to normal T cells. The direct cytotoxicity and observed capping was significantly greater for CLL cells as compared to normal T cells. Cell-mediated and complement-mediated cytotoxicity did not significantly differ between the two cell types. In summary, our data support the hypothesis that alemtuzumab can initiate CLL cell death by crosslinking CD52-enriched lipid rafts. Furthermore, the differential direct cytotoxic effect suggests that CD52 directed antibodies could possibly be engineered to more specifically target CLL cells.

Tetrahydrobenzothiophene inhibitors of hepatitis C virus NS5B polymerase.

A novel series of selective HCV NS5B RNA dependent RNA polymerase inhibitors has been disclosed. These compounds contain an appropriately substituted tetrahydrobenzothiophene scaffold. This communication will detail the SAR and activities of this series.

Predictors of successful labor induction with oral or vaginal misoprostol.

OBJECTIVE: To identify independent predictors of successful labor induction with oral or vaginal misoprostol. METHODS: Women enrolled in four previous randomized trials involving oral or vaginal misoprostol for cervical ripening and labor induction were included in the present cohort study, with dosing of 25-50 microg every 4 to 6 h vaginally (n = 574) or 50 microg every 4 h orally (n = 207). Multiple logistic regression was performed to identify factors independently associated with successful labor induction -- defined as vaginal delivery within 12 h, vaginal delivery within 24 h and spontaneous vaginal delivery. Predictors of Cesarean birth and the need for only one dose of misoprostol were also identified. Variables included in the models were maternal age, weight, height, parity, gravidity, membrane status, route of misoprostol, gestational age, birth weight, and Bishop score and its individual components. RESULTS: Maternal age, height, weight, parity, birth weight, dilatation, effacement and cervical station were associated with vaginal delivery within 24 h of induction. Maternal age, height, weight, nulliparity, birth weight and route of misoprostol were associated with Cesarean birth, with oral misoprostol being associated with a lower rate of Cesarean birth. The need for only one dose of misoprostol was predicted by maternal height, weight, parity, gestational age, Bishop score and route of misoprostol. CONCLUSION: Characteristics of the woman (height, weight, parity), the fetus (birth weight) and some of the individual components of the Bishop score, were associated with successful labor induction, with oral misoprostol being associated with a lower rate of Cesarean birth.

Suppression of polyclonal immunoglobulin production by M-proteins shows isotype specificity.

Monoclonal gammopathies are B cell neoplasms that are characterized by the presence of monoclonal immunoglobulins (M-proteins) in the serum. By an unknown mechanism, the normal polyclonal immunoglobulin levels are frequently reduced in sera of these patients. To assess the role of M-protein isotype in this effect, we used serum protein electrophoresis to quantitate monoclonal and polyclonal immunoglobulins in patients and we used serum immunofixation electrophoresis to determine their M-protein isotype. When divided into populations of 30 patients with IgG M-proteins (mean 2.5 g/dl) and 19 patients with IgM or IgA M-proteins (mean 2.6 g/dl), the mean polyclonal immunoglobulin level was significantly lower in the IgG M-protein population (0.4 g/dl) than the IgM/IgA population (0.8 g/dl). Patients with IgG M-proteins also had significantly lower polyclonal immunoglobulin levels when compared separately with the patients with either IgA or IgM paraproteins. Since the polyclonal immunoglobulin fraction is comprised mostly of IgG, these results give the first direct indication that IgG M-proteins have a greater suppressive effect on polyclonal IgG levels than do M-proteins of other isotypes. These findings suggest that an isotype-specific feedback mechanism could be involved in the normal regulation of serum IgG levels.

Excessive uterine activity accompanying induced labor.

OBJECTIVE: To estimate the incidence and timing of excessive uterine activity accompanying induction of labor with misoprostol using different routes (oral or vaginal) and forms (intact tablet or crushed) and to compare these with dinoprostone gel, oxytocin, and spontaneous labor. METHODS: This retrospective cohort study included 519 women at term who had labor induced and 86 women at term in spontaneous labor. Induction agents included misoprostol, dinoprostone, or oxytocin. Fetal heart rate and uterine activity tracings were analyzed independently by three maternal-fetal medicine physicians. The diagnosis of tachysystole or hyperstimulation required the agreement of two or more reviewers. RESULTS: The incidence of tachysystole was highest with misoprostol administered by vaginal tablet (misoprostol vaginal tablet 50 microg every 4 hours, 48.6%; vaginal tablet crushed 50 microg and suspended in hydroxyethyl gel every 4 hours, 30.7%, P =.009; oral tablet 50 microg every 4 hours, 22.2%, P =.001; oral tablet crushed 50 microg every 4 hours, 15.5%, P <.001; dinoprostone gel, 33.0%, P =.022; intravenous oxytocin, 30.2%, P =.027; and spontaneous onset of labor, 23.3%, P <.001). Hyperstimulation occurred more often with dinoprostone gel (16.5%) than with other forms of induction or spontaneous labor. Hyperstimulation occurred significantly more often with vaginal misoprostol crushed tablet (7.9%) and vaginal misoprostol intact tablet (7.6%) than with crushed oral misoprostol (1.0%) (P =.016 and.018, respectively). There was a shorter time to tachysystole with increasing doses of vaginal misoprostol tablet (P =.01). CONCLUSION: The incidence of tachysystole and hyperstimulation, and time to tachysystole, varied depending on the route and form of misoprostol given.

Transvaginal ultrasound and digital examination in predicting successful labor induction.

OBJECTIVE: To compare transvaginal ultrasound and digital cervical examination in predicting successful induction in post-term pregnancy. METHODS: Transvaginal ultrasound and digital vaginal examinations were performed on 122 women at 41 or more weeks' gestation, immediately before labor induction. Ultrasound assessments of cervical length, dilatation, and presence of funneling were compared with the components of the Bishop score. The primary outcome was the rate of vaginal delivery. Secondary outcomes assessed included the rates of active labor in 12 hours, vaginal delivery in 12 and 24 hours, mean duration of latent phase, and induction to vaginal delivery interval. Linear and multiple logistic regression models were generated to identify factors independently associated with successful induction. RESULTS: No ultrasound characteristic predicted primary or secondary outcomes. Bishop score (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.71, 5.20), cervical position (OR 4.35, 95% CI 1.41, 12.50), and maternal age (OR 1.15, 95% CI 1.01, 1.30) independently predicted vaginal delivery. Maternal weight (OR 0.96, 95% CI 0.94, 0.98), cervical dilatation (OR 6.08, 95% CI 1.70, 21.68), and effacement (OR 2.34, 95% CI 1.16, 4.73) independently predicted active labor in 12 hours. Independent predictors of vaginal delivery in 12 hours were induction method (P <.001), cervical dilatation (OR 11.16, 95% CI 3.17, 39.29), gravidity (OR 2.06, 95% CI 1.13, 3.77), and maternal weight (OR 0.96, 95% CI 0.93, 0.99). Cervical effacement (OR 2.70, 95% CI 1.59, 4.57) and parity (OR 7.10, 95% CI 2.22, 22.72) independently predicted vaginal delivery in 24 hours. Maternal weight, cervical position, and cervical dilatation were independently associated with latent phase labor duration. Factors independently associated with length of induction to delivery interval were parity, cervical effacement, and maternal weight. CONCLUSION: Transvaginal ultrasound does not predict successful labor induction in post-term pregnancy as well as digital cervical examination.

Obesity: assessment and management in primary care.

Obesity is a complex, multifactorial condition in which excess body fat may put a person at health risk. National data indicate that the prevalence of obesity in the United States is increasing in children and adults. Reversing these trends requires changes in individual behavior and the elimination of societal barriers to healthy lifestyle choices. Basic treatment of overweight and obese patients requires a comprehensive approach involving diet and nutrition, regular physical activity, and behavioral change, with an emphasis on long-term weight management rather than short-term extreme weight reduction. Physicians and other health professionals have an important role in promoting preventive measures and encouraging positive lifestyle behaviors, as well as identifying and treating obesity-related comorbidities. Health professionals also have a role in counseling patients about safe and effective weight loss and weight maintenance programs. Recent evidence-based guidelines from the National Heart, Lung, and Blood Institute, as well as recommendations from the American Academy of Pediatrics, American Association of Clinical Endocrinologists/American College of Endocrinology, American Obesity Association, U.S. Clinical Preventive Services Task Force, Institute of Medicine, and World Health Organization can be consulted for information and guidance on the identification and management of overweight and obese patients.

Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial.

BACKGROUND: Intravesical chemotherapy (i.e., placement of the drug directly in the bladder) with mitomycin C is beneficial for patients with superficial bladder cancer who are at high risk of recurrence, but standard therapy is empirically based and patient response rates have been variable, in part because of inadequate drug delivery. We carried out a prospective, two-arm, randomized, multi-institutional phase III trial to test whether enhancing the drug's concentration in urine would improve its efficacy. METHODS: Patients with histologically proven transitional cell carcinoma and at high risk for recurrence were eligible for the trial. Patients in the optimized-treatment arm (n = 119) received a 40-mg dose of mitomycin C, pharmacokinetic manipulations to increase drug concentration by decreasing urine volume, and urine alkalinization to stabilize the drug. Patients in the standard-treatment arm (n = 111) received a 20-mg dose without pharmacokinetic manipulations or urine alkalinization. Both treatments were given weekly for 6 weeks. Primary endpoints were recurrence and time to recurrence. Treatment outcome was examined by use of Kaplan-Meier analysis with log-rank tests. Statistical tests were two-sided. RESULTS: Patients in the two arms did not differ in demographics or history of intravesical therapy. Dysuria occurred more frequently in the optimized arm but did not lead to more frequent treatment termination. In an intent-to-treat analysis, patients in the optimized arm showed a longer median time to recurrence (29.1 months; 95% confidence interval [CI] = 14.0 to 44.2 months) and a greater recurrence-free fraction (41.0%; 95% CI = 30.9% to 51.1%) at 5 years than patients in the standard arm (11.8 months; 95% CI = 7.2 to 16.4 months) and 24.6% (95% CI = 14.9% to 34.3%) (P =.005, log-rank test for time to recurrence). Improvements were found in all risk groups defined by tumor stage, grade, focality, and recurrence. CONCLUSIONS: This study identified a pharmacologically optimized intravesical mitomycin C treatment with statistically significantly enhanced efficacy.

The influence of early transplantation, age, GVHD prevention regimen, and other factors on outcome of allogeneic transplantation for CML following BuCy.

Results in 164 patients who underwent allogeneic marrow transplantation following busulfan and cyclophosphamide over a 15 year period were analyzed. Age (median 37, range 14-66 years) did not significantly affect the incidence of graft-versus-host disease (GVHD), but patients who received methotrexate with cyclosporine had a significantly lower incidence (P = 0.002) of chronic GVHD compared to those who received methylprednisolone with cyclosporine. Hepatic veno-occlusive disease (VOD) occurred less frequently in chronic phase patients (P = 0.002) and in those transplanted shortly after diagnosis (P = 0.001). Five year leukemia-free survival (LFS) for the entire group was 49% (95% CI 41-57%). For 102 patients who underwent transplantation in chronic phase, results were significantly improved by transplantation at a short interval following diagnosis, particularly within 3 months (P = 0.01), by the use of methotrexate and not corticosteroids for GVHD prevention (P = 0.03), and by use of HLA-identical sibling donors (P = 0.01). Age was not a significant adverse prognostic factor and transplantation was successfully performed in individuals up to age 66. Allogeneic transplantation in CML, including older patients and those with unrelated donors, can be most safely and effectively performed shortly after diagnosis.

Acardiac twin pregnancy with neonatal resolution of donor twin cardiomyopathy.

BACKGROUND: Twin reverse arterial perfusion, as with acardiac fetuses, is a rare complication of multifetal pregnancy. Prognosis of the donor twin is guarded because of the high risk of cardiac failure, polyhydramnios, and preterm delivery. CASE: A 40-year-old woman, gravida 4, para 3, was diagnosed at 19 weeks' gestation with a twin pregnancy complicated by an acardiac, acephalic fetus. Serial amniocenteses were done to decompress the hydramnios between 27 and 33 weeks. Ultrasonography showed ventricular septal hypertrophy in the donor twin at 27 weeks, and cesarean delivery was done at 33 weeks. The neonatal course was complicated by hypertrophic cardiomyopathy, which resolved without sequelae by 1 year of age. CONCLUSION: Antenatal sonographic monitoring of interventricular septal thickness can be a useful marker to predict neonatal cardiac sequelae.

Adhesive capsulitis of the shoulder in male cardiac surgery patients.

Two hundred fourteen consecutive male cardiac surgery patients were retrospectively evaluated for the incidence of adhesive capsulitis of the shoulder and were assessed for risk factors. Only male patients were included, as the study took place at a Veteran's hospital. Patients who had no shoulder problems prior to cardiac surgery and were experiencing shoulder pain or stiffness postoperatively underwent history, physical examination, and radiographic studies. Thirty-five patients who had shoulder complaints were identified and evaluated. A 3.3% incidence (seven patients) of adhesive capsulitis of the shoulder in a male post-cardiac surgery population was established.

Autotransplantation following busulfan, etoposide and cyclophosphamide in patients with non-Hodgkin's lymphoma.

The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eighty-two patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progression-free survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248.

Peptide deformylase in Staphylococcus aureus: resistance to inhibition is mediated by mutations in the formyltransferase gene.

Peptide deformylase, a bacterial enzyme, represents a novel target for antibiotic discovery. Two deformylase homologs, defA and defB, were identified in Staphylococcus aureus. The defA homolog, located upstream of the transformylase gene, was identified by genomic analysis and was cloned from chromosomal DNA by PCR. A distinct homolog, defB, was cloned from an S. aureus genomic library by complementation of the arabinose-dependent phenotype of a P(BAD)-def Escherichia coli strain grown under arabinose-limiting conditions. Overexpression in E. coli of defB, but not defA, correlated to increased deformylase activity and decreased susceptibility to actinonin, a deformylase-specific inhibitor. The defB gene could not be disrupted in wild-type S. aureus, suggesting that this gene, which encodes a functional deformylase, is essential. In contrast, the defA gene could be inactivated; the function of this gene is unknown. Actinonin-resistant mutants grew slowly in vitro and did not show cross-resistance to other classes of antibiotics. When compared to the parent, an actinonin-resistant strain produced an attenuated infection in a murine abscess model, indicating that this strain also has a growth disadvantage in vivo. Sequence analysis of the actinonin-resistant mutants revealed that each harbors a loss-of-function mutation in the fmt gene. Susceptibility to actinonin was restored when the wild-type fmt gene was introduced into these mutant strains. An S. aureus Deltafmt strain was also resistant to actinonin, suggesting that a functional deformylase activity is not required in a strain that lacks formyltransferase activity. Accordingly, the defB gene could be disrupted in an fmt mutant.

Hypothyroidism after treatment for nonthyroid head and neck cancer.

OBJECTIVES: To determine the incidence of posttreatment hypothyroidism in patients treated with surgery with or without radiotherapy for advanced-stage nonthyroid head and neck cancer and to make recommendations for its detection. DESIGN: A prospective study to assess the incidence and time frame of occurrence of hypothyroidism in patients by primary tumor site and treatment modality. Thyroid function tests were performed preoperatively, at the first postoperative visit, and then approximately every 6 months. Patients were followed up for up to 3 years. SETTING: Arthur G. James Cancer Hospital and Research Institute, Columbus, Ohio. PATIENTS: A total of 251 patients with nonthyroid head and neck cancer were originally enrolled; 198 patients with evaluable data were studied to determine the incidence of posttreatment hypothyroidism. Approximately 80% of the patients had advanced stage (III or IV) or recurrent cancer. RESULTS: The overall incidence of posttreatment hypothyroidism was 15% in 198 patients followed up for a mean of approximately 12 months. Hypothyroidism developed in 12% of patients treated with nonlaryngeal surgery and radiotherapy. The group undergoing total laryngectomy (with thyroid lobectomy) and radiotherapy had a 61% incidence of hypothyroidism. The average time to detection of hypothyroidism was 8.2 months. CONCLUSIONS: Approximately 15% of patients treated for advanced head and neck cancer with surgery and radiotherapy will develop hypothyroidism. Those treated with total laryngectomy and radiotherapy are at greatest risk.