Hyperthermia and Thermosensitive Liposomes for Improved Delivery of Chemotherapeutic Drugs to Solid Tumors

Lipid-based nanocarriers or liposomes have been proven successful in the delivery of chemotherapeutic agents and are currently applied clinically in the treatment of various types of cancer. Liposomes offer the advantage of a high drug payload, decreased drug toxicity and enhanced drug accumulation at tumor sites. Increased accumulation is due to the relatively leaky tumor vasculature that allows liposome extravasation. Between different types of tumors and even within one tumor, vascular permeability and thus liposome extravasation may differ greatly. Furthermore, upon accumulation of liposomes in the tumor area, drug bioavailability is not guaranteed. At present, these are the major issues for clinically used liposomal drugs

Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer

The factors affecting long-term survival following oesophagectomy for oesophageal cancer are poorly understood. We examined the significance of microscopic tumour involvement at the circumferential resection margin (CRM) on postoperative survival following oesophagectomy. The case notes of 329 patients who underwent a potentially curative oesophagectomy for squamous or adenocarcinoma were reviewed retrospectively. As part of the procedure, all patients underwent an en-bloc resection of their periesophageal tissue. The presence of tumour either at, or within, 1 mm of the CRM was recorded and correlated with their TNM and survival data. A total of 67 patients (20%) were noted to have a positive CRM, of which 40 cases (12%) had tumour at the resection margin and the remainder had tumour within 1 mm of the margin. Univariate analysis showed no statistically significant association between survival and either category of CRM involvement. Multivariate analysis showed that only T-stage, nodal status and tumour grade were prognostic markers. In conclusion, the presence of microscopic tumour at the CRM following an en-bloc oesophagectomy is not a significant prognostic marker

Can group-based reassuring information alter low back pain behavior? A cluster-randomized controlled trial?

Background Low back pain (LBP) is common in the population and multifactorial in nature, often involving negative consequences. Reassuring information to improve coping is recommended for reducing the negative consequences of LBP. Adding a simple non-threatening explanation for the pain (temporary muscular dysfunction) has been successful at altering beliefs and behavior when delivered with other intervention elements. This study investigates the isolated effect of this specific information on future occupational behavior outcomes when delivered to the workforce. Design A cluster-randomized controlled trial. Methods Publically employed workers (n=505) from 11 Danish municipality centers were randomized at center-level (cluster) to either intervention (two 1-hour group-based talks at the workplace) or control. The talks provided reassuring information together with a simple non-threatening explanation for LBP - the ‘functional-disturbance’-model. Data collections took place monthly over a 1-year period using text message tracking (SMS). Primary outcomes were self-reported days of cutting down usual activities and work participation. Secondary outcomes were self-reported back beliefs, work ability, number of healthcare visits, bothersomeness, restricted activity, use of pain medication, and sadness/depression. Results There was no between-group difference in the development of LBP during follow-up. Cumulative logistic regression analyses showed no between-group difference on days of cutting down activities, but increased odds for more days of work participation in the intervention group (OR=1.83 95% CI: 1.08-3.12). Furthermore, the intervention group was more likely to report: higher work ability, reduced visits to healthcare professionals, lower bothersomeness, lower levels of sadness/depression, and positive back beliefs. Conclusion Reassuring information involving a simple non-threatening explanation for LBP significantly increased the odds for days of work participation and higher work ability among workers who went on to experience LBP during the 12-month follow-up. Our results confirm the potential for public-health education for LBP, and add to the discussion of simple versus multidisciplinary interventions

Risk factors for sickness absence due to low back pain and prognostic factors for return to work in a cohort of shipyard workers

The purpose of this study was to determine risk factors for the occurrence of sickness absence due to low back pain (LBP) and to evaluate prognostic factors for return to work. A longitudinal study with 1-year follow-up was conducted among 853 shipyard workers. The cohort was drawn around January 2004 among employees in the shipyard industry. Baseline information was obtained by questionnaire on physical and psychosocial work load, need for recovery, perceived general health, musculoskeletal complaints, sickness absence, and health care use during the past year. During the 1-year follow-up for each subject medical certifications were retrieved for information on the frequency and duration of spells of sickness absence and associated diagnoses. Cox regression analyses were conducted on occurrence and on duration of sickness absence with hazard ratios (HR) with 95% confidence interval (95% CI) as measure of association. During the 1-year follow-up period, 14% of the population was on sick leave at least once with LBP while recurrence reached 41%. The main risk factors for sickness absence were previous absence due to a health problem other than LBP (HR 3.07; 95%CI 1.66–5.68) or previous sickness absence due to LBP (HR 6.52; 95%CI 3.16–13.46). Care seeking for LBP and lower educational level also hold significant influences (HR 2.41; 95%CI 1.45–4.01 and HR 2.46; 95%CI 1.19–5.07, respectively). Living with others, night shift and supervising duties were associated with less absenteeism due to LBP. Workers with a history of herniated disc had a significantly decreased rate of returning to work, whereas those who suffered from hand-wrist complaints and LBP returned to work faster. Prior sick leave due to LBP partly captured the effects of work-related physical and psychosocial factors on occurrence of sick leave. Our study showed that individual and job characteristics (living alone, night shift, lower education, sick leave, or care seeking during the last 12 months) influenced the decision to take sick leave due to LBP. An increased awareness of those frequently on sick leave and additional management after return to work may have a beneficial effect on the sickness absence pattern

An interdisciplinary clinical practice model for the management of low-back pain in primary care: the CLIP project

<p>Abstract</p> <p>Background</p> <p>Low-back pain is responsible for significant disability and costs in industrialized countries. Only a minority of subjects suffering from low-back pain will develop persistent disability. However, this minority is responsible for the majority of costs and has the poorest health outcomes. The objective of the Clinic on Low-back pain in Interdisciplinary Practice (CLIP) project was to develop a primary care interdisciplinary practice model for the clinical management of low-back pain and the prevention of persistent disability.</p> <p>Methods</p> <p>Using previously published guidelines, systematic reviews and meta-analyses, a clinical management model for low-back pain was developed by the project team. A structured process facilitating discussions on this model among researchers, stakeholders and clinicians was created. The model was revised following these exchanges, without deviating from the evidence.</p> <p>Results</p> <p>A model consisting of nine elements on clinical management of low-back pain and prevention of persistent disability was developed. The model's two core elements for the prevention of persistent disability are the following: 1) the evaluation of the prognosis at the fourth week of disability, and of key modifiable barriers to return to usual activities if the prognosis is unfavourable; 2) the evaluation of the patient's perceived disability every four weeks, with the evaluation and management of barriers to return to usual activities if perceived disability has not sufficiently improved.</p> <p>Conclusion</p> <p>A primary care interdisciplinary model aimed at improving quality and continuity of care for patients with low-back pain was developed. The effectiveness, efficiency and applicability of the CLIP model in preventing persistent disability in patients suffering from low-back pain should be assessed.</p

Cryptococcus: from environmental saprophyte to global pathogen.

Cryptococcosis is a globally distributed invasive fungal infection that is caused by species within the genus Cryptococcus which presents substantial therapeutic challenges. Although natural human-to-human transmission has never been observed, recent work has identified multiple virulence mechanisms that enable cryptococci to infect, disseminate within and ultimately kill their human host. In this Review, we describe these recent discoveries that illustrate the intricacy of host-pathogen interactions and reveal new details about the host immune responses that either help to protect against disease or increase host susceptibility. In addition, we discuss how this improved understanding of both the host and the pathogen informs potential new avenues for therapeutic development