Waseem Sharieff

Biopsy versus partial versus gross total resection in older patients with high-grade glioma: a systematic review and meta-analysis

BACKGROUNDnOptimal extent of surgical resection (EOR) of high-grade gliomas (HGGs) remains uncertain in the elderly given the unclear benefits and potentially higher rates of mortality and morbidity associated with more extensive degrees of resection.nnnMETHODSnWe undertook a meta-analysis according to a predefined protocol and systematically searched literature databases for reports about HGG EOR. Elderly patients (≥60 y) undergoing biopsy, subtotal resection (STR), and gross total resection (GTR) were compared for the outcome measures of overall survival (OS), postoperative karnofsky performance status (KPS), progression-free survival (PFS), mortality, and morbidity. Treatment effects as pooled estimates, mean differences (MDs), or risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were determined using random effects modeling.nnnRESULTSnA total of 12 607 participants from 34 studies met eligibility criteria, including our current cohort of 211 patients. When comparing overall resection (of any extent) with biopsy, in favor of the resection group were OS (MD 3.88 mo, 95% CI: 2.14-5.62, P < .001), postoperative KPS (MD 10.4, 95% CI: 6.58-14.22, P < .001), PFS (MD 2.44 mo, 95% CI: 1.45-3.43, P < .001), mortality (RR = 0.27, 95% CI: 0.12-0.61, P = .002), and morbidity (RR = 0.82, 95% CI: 0.46-1.46, P = .514) . GTR was significantly superior to STR in terms of OS (MD 3.77 mo, 95% CI: 2.26-5.29, P < .001), postoperative KPS (MD 4.91, 95% CI: 0.91-8.92, P = .016), and PFS (MD 2.21 mo, 95% CI: 1.13-3.3, P < .001) with no difference in mortality (RR = 0.53, 95% CI: 0.05-5.71, P = .600) or morbidity (RR = 0.52, 95% CI: 0.18-1.49, P = .223).nnnCONCLUSIONSnOur findings suggest an upward improvement in survival time, functional recovery, and tumor recurrence rate associated with increasing extents of safe resection. These benefits did not result in higher rates of mortality or morbidity if considered in conjunction with known established safety measures when managing elderly patients harboring HGGs.

Characterization of clopidogrel hypersensitivity reactions and management with oral steroids without clopidogrel discontinuation.

OBJECTIVESnThe purpose of this study was to characterize clopidogrel hypersensitivity and describe its successful management with oral steroids without clopidogrel discontinuation.nnnBACKGROUNDnHypersensitivity reactions to clopidogrel are poorly understood and present difficulty in management.nnnMETHODSnPatients diagnosed with clopidogrel hypersensitivity after percutaneous coronary intervention underwent evaluation and received oral prednisone without clopidogrel discontinuation. Cutaneous testing was performed after completion of clopidogrel therapy for diagnosis and assessment of cross-reactivity.nnnRESULTSnSixty-two patients representing 1.6% of the percutaneous coronary intervention population developed clopidogrel hypersensitivity during the study period. The mean age was 62 ± 11 years, 71% of patients were male, and 35% reported prior adverse drug reaction. Clopidogrel hypersensitivity manifested as generalized exanthema in 79%, localized skin reaction in 16%, and angioedema or urticaria in 5% of patients. Biopsy of affected areas demonstrated a lymphocyte-mediated delayed hypersensitivity reaction. Complete resolution of hypersensitivity reaction was observed in 61 patients (98%) with a short course of oral prednisone. Cutaneous testing confirmed delayed hypersensitivity reaction to clopidogrel in 34 (81%) and immediate hypersensitivity in 3 of 42 patients (7%) tested. Allergenic cross-reactivity was observed for ticlopidine in 10 (24%), prasugrel in 7 (17%), and both ticlopidine and prasugrel in 3 patients (7%). Histological examination showed lymphocyte-mediated hypersensitivity in abnormal patch test areas.nnnCONCLUSIONSnClopidogrel hypersensitivity is manifested as generalized exanthema and is caused by a lymphocyte-mediated delayed hypersensitivity in most patients. This can be managed with oral steroids without clopidogrel discontinuation. Allergenic cross-reactivity with ticlopidine, prasugrel, or both is present in a significant number of patients with clopidogrel hypersensitivity.

Fractionated stereotactic radiosurgery with concurrent temozolomide chemotherapy for locally recurrent glioblastoma multiforme: a prospective cohort study.

Local recurrence represents a significant challenge in the management of patients with glioblastoma multiforme. Salvage treatment options are limited by lack of clinical efficacy. Recent studies have demonstrated a significant response rate and acceptable toxicity with the use of fractionated stereotactic radiosurgery in this patient population. Our primary objective was to determine the efficacy and toxicity of fractionated stereotactic radiosurgery combined with concurrent temozolomide chemotherapy as a salvage treatment for recurrent glioblastoma multiforme. We prospectively collected treatment and outcome data for patients having fractionated stereotactic radiosurgery for locally recurrent glioblastoma multiforme after radical radiotherapy. Eligible patients had a maximum recurrence diameter of 60 mm without causing significant mass effect. The gross tumor volume was defined as the enhancing lesion on an enhanced fine-slice T1 (spin–lattice) magnetic resonance imaging, and a circumferential setup margin of 1 mm was used to define the planning target volume. All patients were treated using robotic radiosurgery with three dose/fractionation schedules ranging from 25 to 35 Gy in five fractions, depending on the maximum tumor diameter. Concurrent temozolomide 75 mg/m2 was prescribed to all patients. Tumor response was judged using the Macdonald criteria, and toxicity was assessed using the CTCAE (Common Terminology Criteria for Adverse Events). A total of 31 patients were enrolled in this study. The median overall survival was 9 months, and progression-free survival was 7 months. The 6-month progression-free survival was 60% with a 95% confidence interval of 43%–77%. The a priori stratification factor of small tumor diameter was shown to predict overall survival, while time to recurrence was not predictive of progression-free or overall survival. Three patients experienced grade 3 acute toxicity that responded to increased steroid dosing. One patient experienced a grade 4 acute toxicity that did not respond to increased steroids but did respond to anti-angiogenic therapy. Fractionated stereotactic radiosurgery with concurrent temozolomide has shown good short-term clinical and radiologic control with manageable acute toxicity. This regimen appears to provide superior efficacy to either temozolomide or fractionated radiosurgery alone. The results of this study support the continued evaluation of this regimen.

Is cooking food in iron pots an appropriate solution for the control of anaemia in developing countries? A randomised clinical trial in Benin

OBJECTIVEnTo evaluate the effect of two types of iron pots on haemoglobin (Hb) and serum ferritin (SF) concentrations in young children (6-24 months), adolescent girls (11-15 years) and women of reproductive age (15-44 years), whose households were provided with iron pots for cooking food over a period of 6 months, compared with controls.nnnDESIGN AND METHODSnWe randomly assigned 161 households including 339 individuals from the three subgroups to cast iron pots, blue steel pots or oral iron supplements (control). In the control group, children received micronutrient Sprinkles, and adolescent girls and women received iron tablets daily for 6 months. We measured Hb, SF and C-reactive protein concentrations at baseline and 6 months, and compared groups using regression models.nnnRESULTSnAnaemia prevalence (Hb < 110 g l(-1) in infants, Hb < 120 g l(-1) in girls or women) was 47% (cast iron group), 50% (blue steel group) and 50% (control) at baseline. At 6 months, there were no significant differences in Hb concentrations among groups; however, differences in SF concentrations were significant (P < 0.0001)--the control group had higher SF concentrations compared with the groups using iron pots. Also, differences in the prevalence of iron-deficiency anaemia (IDA; anaemia plus SF < 15 microg l(-1)) were almost significant between cast iron and control groups (P = 0.08), and blue steel and control groups (P = 0.05).nnnCONCLUSIONnThere is no evidence that iron cooking pots are effective against IDA. Further research is warranted to determine whether the iron leached from the pots is bioavailable.

The benefit of deep inspiration breath hold: evaluating cardiac radiation exposure in patients after mastectomy and after breast-conserving surgery

BackgroundThis study aims to evaluate the reduction of cardiac radiation dose and volume with deep inspiration breath hold (DIBH) technique compared to free breathing (FB) in patients with left-sided breast cancer. The study also aims to evaluate whether the benefits of DIBH vary in patients who had whole breast radiotherapy (RT) after breast-conserving surgery (BCS) and those who had chest wall RT post-mastectomy (M).MethodsFB and DIBH plans were generated for 15 consecutive post-BCS patients and 17 post-M patients who underwent RT with DIBH using varian real-time position management (RPM) system. Cardiac shields were used in all post-BCS plans, provided that clinical treatment volume coverage was not compromised, while chest wall coverage took priority in post-M plans. The prescribed dose was 50xa0Gy in 25 fractions for the whole breast or the chest wall. Parameters of interest were cardiac V5, mean LAD dose, maximum LAD dose, and mean heart dose. The impact of DIBH was compared in post-BCS and post-M patients using paired t tests. To gauge clinically meaningful outcome, the proportion of patients with V5xa0<xa05xa0% and mean cardiac dose <2xa0Gy were compared using McNemar’s test.ResultsDIBH decreased V5 by an absolute 4.5xa0% (2.3 vs. 6.8xa0%; pxa0<xa00.0001) in post-M group, and by an absolute 2.4xa0% (1.3 vs. 3.7xa0%; pxa0=xa00.0028) in post-BCS group. DIBH decreased the mean heart dose by 107.0xa0cGy (127.4 vs. 234.4xa0cGy; pxa0=xa00.0002) in post-M group, and by 58.9xa0cGy (82.2 vs. 141.1xa0cGy; pxa0=xa00.0012) in post-BCS group. DIBH decreased mean LAD by 1201.6xa0cGy (670 vs. 1872.5xa0cGy; pxa0=xa00.0006) in post-M group, and by 799.0xa0cGy (425.3 vs. 1224.3xa0cGy; pxa0=xa00.0003) in post-BCS group. DIBH also decreased max LAD dose by 1244.3xa0cGy (2776.0 vs. 4020.3xa0cGy; pxa0=xa00.0014) in post-M group, and by 1856.3xa0cGy (1898.7 vs. 3754.9xa0cGy; pxa0=xa00.0005) in post-BCS group. In post-BCS group, cardiac V5xa0<xa05xa0% was achieved in 10/15 (67xa0%) FB patients, and in 15/15 (100xa0%) DIBH patients (pxa0=xa00.002), and mean heart dose <2xa0Gy was achieved in 12/15 (80xa0%) FB patients and in 15/15 (100xa0%) DIBH patients (pxa0<xa00.001). This compares with post-M group, in which V5xa0<xa05xa0% was achieved in 6/17 (35xa0%) FB patients and in 16/17 (94xa0%) DIBH patients (pxa0=xa00.05), and mean heart dose <2xa0Gy was achieved in 7/17 FB (41xa0%) an 16/17 DIBH patients (94xa0%) (pxa0=xa00.03).ConclusionThe results of this study suggest that there is considerable reduction in cardiac exposure in most patients with DIBH compared to FB, although less reduction is observed in the post-BCS patients. The use of cardiac shields and collimators/gantry adjustments, more readily applicable for post-BCS cases, may limit the additional benefits of DIBH. In an environment where DIBH availability is limited, the result of this study supports the preferential use of DIBH in post-M patients over post-BCS patients.

The Technique, Resources and Costs of Stereotactic Body Radiotherapy of Prostate Cancer: A Comparison of Dose Regimens and Delivery Systems.

Robotic system has been used for stereotactic body radiotherapy (SBRT) of prostate cancer. Arc-based and fixed-gantry systems are used for hypofractionated regimens (10-20 ractions) and the standard regimen (39 fractions); they may also be used to deliver SBRT. Studies are currently underway to compare efficacy and safety of these systems and regimens. Thus, we describe the technique and required resources for the provision of robotic SBRT in relation to the standard regimen and other systems to guide investment decisions. Using administrative data of resource volumes and unit prices, we computed the cost per patient, cost per cure and cost per quality adjusted life year (QALY) of four regimens (5, 12, 20 and 39 fractions) and three delivery systems (robotic, arc-based and fixed-gantry) from a payer’s perspective. We performed sensitivity analyses to examine the effects of daily hours of operation and in-room treatment delivery times on cost per patient. In addition, we estimated the budget impact when a robotic system is preferred over an arc-based or fixed-gantry system. Costs of SBRT were

Interventional cardiology fellowship training in Canada: a report card using standardized criteria.

6333/patient (robotic),

Robotic radiosurgery for the treatment of 1-3 brain metastases: a pragmatic application of cost-benefit analysis using willingness-to-pay.

4368/patient (arc-based) and

Robotic radiosurgery for the treatment of one to three brain metastases: A pragmatic application of cost-benefit analysis using willingness to pay.

4443/patient (fixed-gantry). When daily hours of operation were varied, the cost of robotic SBRT varied from

The technique and cost of radiosurgery for the treatment of 1-3 brain metastases.

9324/patient (2 hours daily) to