Evidence based tools to improve efficiency of currently administered oncotherapies for tumors of the hepatopancreatobiliary system

Hepatopancreatobiliary tumors are challenging to treat, and the advanced or metastatic forms have a very low 5-year survival rate. Several drug combinations have been tested, and new therapeutic approaches have been introduced in the last decades, including radiofrequency and heat based methods. Hyperthermia is the artificial heating of tumors by various biophysical methods that may possess immunostimulant, tumoricidal, and chemoradiotherapy sensitizer effects. Both whole-body and regional hyperthermia studies have been conducted since the 1980s after the introduction of deep-seated tumor hyperthermia techniques. Results of the effects of hyperthermia in hepatocellular and pancreatic cancer are known from several studies. Hyperthermia in biliary cancers is a less investigated area. High local and overall responses to treatment, increased progression-free and overall survival, and improved laboratory and quality-of-life results are associated with hyperthermia in all three tumor types. With the evolution of chemotherapeutic agents and the introduction of newer techniques, the combination of adjuvant hyperthermia with those therapies is advantageous and has not been associated with an increase in alarming adverse effects. However, despite the many positive effects of hyperthermia, its use is still only known at the experimental level, and its concomitant utilization in routine cancer treatment is not certain because of the lack of thorough clinical studies.     

Aberrant metastatic behavior and particular features of early gastric cancer

In this paper, we have focused on the metastatic behavior of EGC and its particularities. The main factors that are currently considered as predictors of the metastatic behavior and that are used in the therapeutic decision (endoscopic resection vs surgical removal) are the tumor size (upper or bellow 2 cm), depth of infiltration, angiolymphatic invasion, the presence or absence of ulceration, and histologic type (undifferentiated vs differentiated carcinomas). However, most of the metastatic cases were published as case reports or case series. This is the reason why a proper estimation of metastatic risk in EGC is not well known. To date, 79 cases presenting bone metastases, three reports of brain metastases, and one EGC that was associated with skin metastasis were published. However, occult metastasis, lymph node micrometastasis, and skip metastasis can also occur and should be identified. Making a synthesis of the literature data that is correlated with our experience, we finally proposed the inclusion of the six Japanese subgrouping system, tumor size, angiolymphatic invasion, and micrometastasis as components of the pTNM staging system, which should be particularly adapted for EGC.     

Development of multi-criteria decision analysis (MCDA) framework for off-patent pharmaceuticals – an application on improving tender decision making in Indonesia

Background

Off-patent pharmaceuticals (OPPs) hold vital importance in meeting public health objectives, especially in developing countries where resources are limited. OPPs are comprised of off-patent originals, branded generics and unbranded generics; nonetheless, these products are not identical and often there are differences in their equivalence, manufacturing quality standards and reliability of supply. This necessitates reconsideration of the lowest price policy objective in pharmaceutical decision making. The aim of this study was to develop a Multi-Criteria Decision Analysis (MCDA) framework through a pilot workshop to inform the national procurement of OPPs in Indonesia.

Methods

An initial list of potentially relevant criteria was identified based on previous work and a literature review. In a 2-day pilot policy workshop, twenty local experts representing different stakeholder groups and decision-making bodies selected the final criteria, approved the scoring function for each criterion, and assigned weights to each criterion.

Results

An MCDA framework was proposed for OPP drug decision making in developing countries, which included price and 8 non-price criteria. Based on the pilot policy workshop 6?+?1 criteria were considered relevant for Indonesia: pharmaceutical price (40% weight), manufacturing quality (18.8%), equivalence with the reference product (12.2%), product stability and drug formulation (12.2%), reliability of drug supply (8.4%), real world clinical or economic outcomes, such as adherence or non-drug costs (4.2%) and pharmacovigilance (3.6%).

Conclusions

According to the pilot policy workshop, other criteria apart from price need to be strengthened in the tendering process. The introduction of additional criteria for OPP procurement in an MCDA framework creates incentives for manufacturers to invest into improved manufacturing standards, equivalence proof, product quality, reliability of supply or even additional real-world data collection, which ultimately may result in more health gain for the society.

     

Experimental evaluation of microsurgical repair of the lingual nerve

Epineural microsurgical repair of the lingual nerve has been shown to be effective in leading to return of sensation in an animal model. Cadaver dissections have provided information regarding surgical access to the operative site, some possible anatomic variations that may be encountered, and a method for nerve repositioning to allow a gain in length.     

Quantitative Longitudinal Evaluation of Diaschisis-Related Cerebellar Perfusion and Diffusion Parameters in Patients with Supratentorial Hemispheric High-Grade Gliomas After Surgery

Decreased cerebral blood volume (CBV) in contralateral cerebellar gray matter (cGM) in conjunction with cerebellar white matter (cWM) damage, consistent with crossed cerebro-cerebellar diaschisis (cCCD) develop following supratentorial hemispheric stroke. In this study, we investigated the longitudinal evolution of diaschisis-related cerebellar perfusion and diffusion tensor-imaging (DTI) changes in patients after surgery for supratentorial brain tumors. Eight patients (M:F 5:3, age 8–22 years) who received surgery for supratentorial high-grade gliomas were evaluated. Initial MRI studies were performed 19–54 days postoperatively, with follow-ups at 2- to 3-month intervals. For each study, parametric maps of the cerebellum were generated and coregistered to T1-weighted images that had been previously segmented for cGM and cWM. Aggregate mean values of CBV, cerebral blood flow (CBF), and fractional anisotropy (FA) were obtained separately for cGM and cWM, and asymmetry indices (AIs) were calculated. Hemodynamic changes were more robust in cGM than in cWM. Seven patients showed decreased perfusion within cGM contralateral to the supratentorial lesion on the first postoperative study, and asymmetry was significant for both CBV (p?=?0.008) and CBF (p?p?p?=?0.0003), without evidence of subsequent recovery. Diaschisis-related hemodynamic alterations within cGM appear on early postoperative studies, but CBV recovers over time. Conversely, cWM DTI changes are delayed and progressive. Although the clinical correlates of cCCD are yet to be elucidated, better understanding of longitudinal structural and hemodynamic changes within brain remote from the area of primary insult could have implications in research and clinical rehabilitative strategies.     

Anterior segment parameters associated with extramuscular manifestations in polymyositis and dermatomyositis

AIM: To evaluate the efficacy and safety of high-dose ultrasound cyclo-plasty (UCP) for the treatment of refractory glaucoma in Chinese patients. METHODS: In this 6-month retrospective study, 37 eyes of 37 patients suffering from severe glaucoma with uncontrolled intraocular pressure (IOP) of ≥21 mm Hg underwent 8-s ultrasonic cyclocoagulation with ten active piezoelectric elements. A complete ophthalmic examination was performed before and at 1d, 1, 3, 6mo after UCP. Therapeutic success was defined as IOP reduction from baseline ≥20% and IOP > 5 mm Hg without adding new glaucoma medication compare to baseline at the 6-month follow-up visit. In addition to mean IOP at each follow-up visit, medications used and complications were also detected and compared to baseline. RESULTS: After UCP procedure, the mean IOP was significantly reduced (P<0.01) from the preoperative 44.1±11.9 mm Hg to postoperative 26.7±11.8 mm Hg at 3mo, and 30.4±14.5 mm Hg at 6mo. The overall mean IOP reductions achieved at 3 and 6mo were 39% and 31%. Sixty-one percent of patients responded well to UCP treatment with a mean IOP reduction of 48% at 3mo and 42% at 6mo. Ocular pain in most of patients were alleviated. No serious intraoperative or postoperative complications occurred. CONCLUSION: High-dose UCP treatment is an effective and safe procedure to reduce IOP in Chinese patients with severe glaucoma.     

The past,present, and future of telemedicine for Parkinson's disease

Travel distance, growing disability, and uneven distribution of doctors limit access to care for most Parkinson's disease (PD) patients worldwide. Telemedicine, the use of telecommunications technology to deliver care at a distance, can help overcome these barriers. In this report, we describe the past, present, and likely future applications of telemedicine to PD. Historically, telemedicine has relied on expensive equipment to connect single patients to a specialist in pilot programs in wealthy nations. As the cost of video conferencing has plummeted, these efforts have expanded in scale and scope, now reaching larger parts of the world and extending the focus from care to training of remote providers. Policy, especially limited reimbursement, currently hinders the growth and adoption of these new care models. As these policies change and technology advances and spreads, the following will likely develop: integrated care networks that connect patients to a wide range of providers; education programs that support patients and health care providers; and new research applications that include remote monitoring and remote visits. Together, these developments will enable more individuals with PD to connect to care, increase access to expertise for patients and providers, and allow more‐extensive, less‐expensive participation in research. © 2014 International Parkinson and Movement Disorder Society