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  • Something Must Be Wrong with the Implementation of Cancer-pain Treatment Guidelines. A Lesson from Referrals to a Pain Clinic

    Objective: The World Health Organization’s (WHO) guidelines for cancer pain management were intentionally made simple in order to be widely implemented by all physicians treating cancer patients. Referrals to pain specialists are advised if pain does not improve within a short time. The present study examined whether or not a reasonable use of the WHO guideline was made by non-pain specialists prior to referral of patients with cancer-related pain to a pain clinic. Methods: Cancer patients referred to a pain specialist completed several questionnaires including demographics, medical history, and cancer-related pain; the short-form McGill Pain Questionnaire (SF-MPQ); and the Short Form Health Survey SF-12. Data from referral letters and medical records were obtained. Treatments recommended by pain specialists were recorded and categorized as “unjustified” if they were within the WHO ladder framework, or “justified” if they included additional treatments. Results: Seventy-three patients (44 women, 29 men) aged 55 years (range, 25–85) participated in the study. Their pain lasted for a mean of 6 (1–192) months. Mean pain intensity scores on a 0–10 numerical rating scale were 7 (2–10) at rest and 8 (3–10) upon movement. Most patients complied with their referring physician’s recommendations and consumed opioids. Adverse events were frequent. No significant correlation was found between the WHO analgesic medication step used and mean pain levels reported. There were 63 patient referrals (85%) categorized as “unjustified,” whereas only 11 patients (15%) required “justified” interventions. Conclusions: These findings imply that analgesic treatment within the WHO framework was not reasonably utilized by non-pain specialists before referring patients to pain clinics.
  • The Development of Robotic Technology in Cardiac and Vascular Interventions

    Robotic technology has been used in cardiovascular medicine for over a decade, and over that period its use has been expanded to interventional cardiology and percutaneous coronary and peripheral vascular interventions. The safety and feasibility of robotically assisted interventions has been demonstrated in multiple studies ranging from simple to complex coronary lesions, and in the treatment of ileofemoral and infrapopliteal disease. These studies have shown a reduction in operator exposure to harmful ionizing radiation, and the use of robotics has the intuitive benefit of alleviating the occupational hazard of operator orthopedic injuries. In addition to the interventional operator benefits, robotically assisted intervention has the potential also to be beneficial for patients by allowing more accurate lesion length measurement, stent placement, and patient radiation exposure; however, more investigation is required to elucidate these benefits fully.
  • Less is More: Modern Neonatology

    Iatrogenesis is more common in neonatal intensive care units (NICUs) because the infants are vulnerable and exposed to prolonged intensive care. Sixty percent of extremely low-birth-weight infants are exposed to iatrogenesis. The risk factors for iatrogenesis in NICUs include prematurity, mechanical or non-invasive ventilation, central lines, and prolonged length of stay. This led to the notion that “less is more.” In the delivery room delayed cord clamping is recommended for term and preterm infants, and suction for the airways in newborns with meconium-stained fluid is not performed anymore. As a symbol for a less aggressive attitude we use the term neonatal stabilization rather than resuscitation. Lower levels of oxygen saturations are accepted as normal during the first 10 minutes of life, and if respiratory assistance is needed, we no longer use 100% oxygen but 0.21–0.3 FiO2, depending on gestational age and the level of oxygen saturation. We try to avoid endotracheal ventilation by using non-invasive respiratory support and administering continuous positive airway pressure early on, starting in the delivery room. If surfactant is needed, non-invasive methods of surfactant administration are utilized. Use of central lines is shortened, and early feeding of human milk is the routine. Permissive hypercapnia is allowed, and continuous non-invasive monitoring not only of the O2 but also of CO2 is warranted. “Kangaroo care” and Newborn Individualized Developmental Care and Assessment Program (NIDCAP) together with a calm atmosphere with parental involvement are encouraged. Whether “less is more,” or not enough, is to be seen in future studies.
  • Jewish Values in Medical Decision-making for Unrepresented Patients: A Ritualized Approach

    Determining appropriate care for patients who cannot speak for themselves is one of the most challenging issues in contemporary healthcare and medical decision-making. While there has been much discussion relating to patients who left some sort of instructions, such as an advance directive, or have someone to speak on their behalf, less has been written on caring for patients who have nobody at all available to speak for them. It is thus crucial to develop clear and rigorous guidelines to properly care for these patients. The Jewish tradition offers an important perspective on caring for unrepresented patients and determining approaches to guide care providers. This article develops an understanding of fundamental Jewish principles that can provide clear guidance in navigating this challenge. It applies those values to a specific set of suggested behaviors, one of which adds a novel ritualized component to what has been recommended by bioethicists in the past.
  • Head and Neck Cancers in Developing Countries

    Head and neck cancers are the most common cancers in developing countries, especially in Southeast Asia. Head and neck cancers are more common in males compared to females. This is mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC). HNSCC in the developing world differ from those in the Western world in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to health care, and poor treatment infrastructure pose a major challenge in management of these cancers. The annual GDP (gross domestic product) spent on health care is very low in developing countries compared to the developed countries. Cancer treatment leads to a significant financial burden on the cancer patients and their families. Several health programs have been implemented to curb this rising burden of disease. The main aims of these health programs are to increase awareness among people regarding tobacco and to improve access to health care facilities, early diagnosis, treatment, and palliative care.
  • Transnasal Flexible Fiberoptic in-office Laryngeal Biopsies—Our Experience with 117 Patients with Suspicious Lesions

    Objective: To compare pathologic results obtained via in-office transnasal fiberoptic laryngoscopy (TFL) to those of subsequent direct laryngoscopy in order to assess the accuracy of TFL as a diagnostic tool. Patients: One hundred and seventeen patients with suspicious laryngeal lesions. Methods: All patients underwent in-office biopsies. All patients with malignant diagnosis were referred to treatment. All patients with benign diagnosis or carcinoma in situ were referred to direct laryngoscopy for definitive diagnosis. The pathological results of the specimens from both procedures were compared. Results: Adequate tissue for diagnostic purposes was obtained in 110 of 117 in-office transnasal fiberoptic laryngoscopy biopsies (94.0%). The biopsy results revealed invasive carcinoma in 42 patients (38.2%), carcinoma in situ (CIS) in 17 patients (15.4%), and benign lesions in 51 patients (46.4%). All patients with benign pathologies and carcinoma in situ were referred to biopsy under direct laryngoscopy (five patients refused and were removed from the statistics). The final pathologies identified from the biopsies on direct laryngoscopy revealed that there was an underestimation of the transnasal fiberoptic laryngoscopy results in 33 patients (a false negative rate of 31.4%, 33/105) and an overestimation in one patient. The sensitivity of transnasal fiberoptic laryngoscopy biopsy compared with direct laryngoscopy biopsy was 70.6% and the specificity was 96.7%. Conclusions: TFL with biopsy is easy, safe, and cost-effective but raises serious doubts about its clinical value due its low sensitivity rate for diagnosing suspicious lesions of the larynx. As such, it is recommended that all patients with a suspicious lesion diagnosed by TFL biopsy as being benign or CIS should be referred to direct laryngoscopy for verification of the findings.
  • ADAMTS-13 in the Diagnosis and Management of Thrombotic Microangiopathies

    Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system causes microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management.
  • Changing the Face of Diabetic Care with Haptoglobin Genotype Selection and Vitamin E

    Research over the past 10 years in our laboratory has led to two major findings. The first is that haptoglobin (Hp) genotype can predict the risk of developing vascular complications in individuals with diabetes mellitus (DM), and the second, more far-reaching discovery, is that vitamin E treatment can significantly reduce vascular complications in individuals with DM and the Hp 2-2 genotype. The former finding has been well documented in numerous studies which included over 50,000 patients of diverse geographical and ethnic backgrounds. The latter discovery is more recent and less well accepted by the medical community due to confounding reports over the past 30 years regarding the efficacy of vitamin E treatment for vascular disease. We propose that the benefit of vitamin E treatment was not obvious in earlier studies due to the absence of any genetic basis for patient selection. Our studies dividing DM individuals into vitamin E treatment subgroups based on Hp genotype show a clear benefit for individuals of the Hp 2-2 genotype, while patients carrying the other two Hp genotypes are not affected or may be adversely affected by receiving vitamin E. These findings may explain the overall lack of benefit seen in previous vitamin E studies and emphasize the importance of carefully selecting which patients should receive vitamin E therapy. The pharmacogenomic paradigm discussed in this review potentially could result in a dramatic improvement in the health of millions of individuals worldwide using a treatment that is both accessible and affordable to all.
  • Systems Biology and P4 Medicine: Past, Present, and Future

    Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB) has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes) for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.). The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to detect and treat perturbations in healthy individuals long before disease symptoms appear, thus optimizing the wellness of individuals and avoiding disease. P4 medicine will 1) improve health care, 2) reduce the cost of health care, and 3) stimulate innovation and new company creation. Health care is not the only subject that can benefit from such integrative, cross-disciplinary, and systems-driven platforms and cultures. Many other challenges plaguing our planet, such as energy, environment, nutrition, and agriculture can be transformed by using such an integrated and systems-driven approach.
  • Robotics in Cardiac Surgery: Past, Present, and Future

    Robotic cardiac operations evolved from minimally invasive operations and offer similar theoretical benefits, including less pain, shorter length of stay, improved cosmesis, and quicker return to preoperative level of functional activity. The additional benefits offered by robotic surgical systems include improved dexterity and degrees of freedom, tremor-free movements, ambidexterity, and the avoidance of the fulcrum effect that is intrinsic when using long-shaft endoscopic instruments. Also, optics and operative visualization are vastly improved compared with direct vision and traditional videoscopes. Robotic systems have been utilized successfully to perform complex mitral valve repairs, coronary revascularization, atrial fibrillation ablation, intracardiac tumor resections, atrial septal defect closures, and left ventricular lead implantation. The history and evolution of these procedures, as well as the present status and future directions of robotic cardiac surgery, are presented in this review.