Incidence and treatment costs of severe bacterial infections among people who inject heroin: A cohort study in South London, England.

BACKGROUND: People who inject drugs often get bacterial infections. Few longitudinal studies have reported the incidence and treatment costs of these infections. METHODS: For a cohort of 2335 people who inject heroin entering treatment for drug dependence between 2006 and 2017 in London, England, we reported the rates of hospitalisation or death with primary causes of cutaneous abscess, cellulitis, phlebitis, septicaemia, osteomyelitis, septic arthritis, endocarditis, or necrotising fasciitis. We compared these rates to the general population. We also used NHS reference costs to calculate the cost of admissions. RESULTS: During a median of 8.0 years of follow-up, 24 % of patients (570/2335) had a severe bacterial infection, most commonly presenting with cutaneous abscesses or cellulitis. Bacterial infections accounted for 13 % of all hospital admissions. The rate was 73 per 1000 person-years (95 % CI 69-77); 50 times the general population, and the rate remained high throughout follow-up. The rate of severe bacterial infections for women was 1.50 (95 % CI 1.32-1.69) times the rate for men. The mean cost per admission was £4980, and we estimate that the annual cost of hospital treatment for people who inject heroin in London is £4.5 million. CONCLUSIONS: People who inject heroin have extreme and long-term risk of severe bacterial infections

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

Treatment of high-risk neuroblastoma

Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose 131I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB

Flare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tamoxifen may occasionally precipitate serious and potentially life-threatening hypercalcemia. However, to date, this has not been documented with aromatase inhibitors.</p> <p>Case presentation</p> <p>A 65-year-old Japanese woman with liver metastasis from breast cancer was admitted to our hospital with vomiting, anorexia, fatigue, arthralgia, muscle pain and dehydration. She had started a course of letrozole five weeks earlier. Our patient's calcium level was 11.6 mg/dL. She was rehydrated and elcatonin was administered. Our patient's parathyroid hormone and parathyroid hormone-related protein levels were not increased and a bone scintigram revealed no evidence of skeletal metastasis. After our patient's serum calcium level returned to within the normal range, letrozole was restarted at one-half of the previous dose (1.25 mg). There were no episodes of hypercalcemia. However, 84 days after restarting letrozole, our patient again complained of arthralgia and treatment was changed to toremifene. During these periods, repeated ultrasonograms revealed no progression of liver metastasis.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of flare hypercalcemia after treatment with letrozole in a patient with metastatic breast cancer.</p

Comparison of Doxorubicin Plus Docetaxel Neoadjuvant Chemotherapy with Doxorubicin Plus Vinorelbine in Primary Breast Cancer

Purpose: This study was performed to compare the therapeutic efficacy and toxicity of doxorubicin plus docetaxel neoadjuvant chemotherapy (NC) with doxorubicin plus vinorelbine NC. Methods: Fifty-three patients underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50 mg/m 2) plus docetaxel (75 mg/m 2) administered every 3 weeks (AD), while 49 patients underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50 mg/m 2) and vinorelbine (25 mg/m 2) administered every 3 weeks (AN). Response rate and treatment-related toxicities were analyzed by administered chemotherapeutics. Response to NC was also analyzed according to clinicobiological characteristics of the primary tumors. Results: Clinical response was observed in 66 % with AN and 81.6 % with AD chemotherapy. A complete pathologic response (pCR) was confirmed in 6 patients (11.3%) with AN and in 7 patients (14.3%) with AD afte

Letrozole as upfront endocrine therapy for postmenopausal women with hormone-sensitive breast cancer: BIG 1-98

The BIG 1-98 trial is a large, randomized, independently conducted clinical trial designed to compare the efficacy of upfront letrozole versus tamoxifen monotherapy and to compare sequential or up-front use of letrozole and/or tamoxifen as an early adjuvant therapy for patients with early breast cancer. We report on the results from the primary core analysis of the BIG 1-98 trial of 8,010 patients, which compares monotherapy with letrozole versus tamoxifen. This pre-planned core analysis allowed the use of patient data from the monotherapy arms of letrozole and tamoxifen and from the sequential arms prior to the drug switch point. Patients randomized to letrozole had a 19% improved disease-free survival (hazard ratio [HR] = 0.81; P = 0.003), due especially to reduced distant metastases (HR = 0.73; P = 0.001). A 14% risk reduction of fatal events in favor of letrozole was also observed (P = NS). The results from the monotherapy arms alone confirmed the findings from the primary core analysis. Based on the results from this trial, the aromatase inhibitor letrozole (Femara®) is currently recommended as a part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer and has recently been approved in the early adjuvant setting in both Europe and the United States. A subsequent analysis after additional follow-up will address the question of monotherapy versus sequential therapy