Problem In Management Of Patients Research Articles

Abstract 4685: Characterization of variants of uncertain significance (VUS) in breast and ovarian cancer predisposition genes

Abstract Panel-based germline genetic testing of established breast and ovarian cancer predisposition genes is widely used in high-risk clinics to inform on risks of breast and ovarian cancer. While most protein truncating mutations identified in predisposition genes are associated with moderate to high risks of these cancers, variants of uncertain significance (VUS), in the form of missense and intronic variants, have an undefined relevance to cancer. Many hundreds of VUS in BRCA1 and BRCA2 identified by clinical genetic testing over the last 20 years still have uncertain clinical relevance. In addition, VUS in other known predisposition genes are being identified by current panel-testing in up to 10% of individuals without BRCA1 or BRCA2 mutations. These VUS cause problems in cancer risk estimation and clinical management of patients undergoing clinical genetic testing. In an effort to evaluate the clinical significance of VUS in cancer predisposition genes we have developed functional assays that characterize the impact of the variants on the functions of the proteins encoded by the predisposition genes. In particular, a homology directed repair reporter assay providing a quantitative measure of homologous recombination repair of DNA double strand breaks has been developed for characterization of VUS in homologous recombination associated genes. When applied to 13 known pathogenic and 30 known neutral variants from the DNA binding domain of BRCA2, this assay exhibits 100% specificity and 100% sensitivity. Based on these results a model estimating the probability of pathogenicity of each BRCA2 VUS was developed. The HDR assay and probability model has now been applied to 230 BRCA2 VUS identified through genetic testing. Here we identify 80 BRCA2 variants that are deficient in HDR activity. We further combined these results with prior probabilities of pathogenicity derived from the sequence based Align GVGD in silico prediction model to estimate the posterior probability of pathogenicity for each VUS. Our results suggest that in the absence of family based segregation information, results from the HDR functional assay and in silico prediction models can be used to predict the pathogenicity of BRCA2 VUS. The assay has also been used to characterize VUS in the PALB2 and RAD51C predisposition genes, leading to identification of a subset of missense variants that are deficient in HDR repair activity and may be associated with increased risk of breast and ovarian cancer. These results will prove useful for improved risk assessment of carriers of these BRCA2, PALB2 and RAD51C variants and their family members and for validation of other approaches to mutation classification. Citation Format: Fergus J. Couch, Hermela Shimelis, Andreas Schroeder, Chunling Hu, Emily Hallberg, Gary Lipton, Edwin Iversen, Noralane M. Lindor. Characterization of variants of uncertain significance (VUS) in breast and ovarian cancer predisposition genes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4685. doi:10.1158/1538-7445.AM2015-4685

Psychological health state of neurology nurses and the intervention study

Objective To investigate the main source of stress, psychological health and intervention methods of neurology nurses so as to provide reference for improving psychological health state of nurses. Methods A total of 40 nurses in department of internal medicine in our hospital were investigated by job stressors questionnaire, symptom checklist(SCL-90 scale),and data were compared with the national norm;and to take measures before and after the intervention were compared and analyzed. Results Neurology nurses'work pressure source was as follows:the nursing profession and work problems, workload and time allocation, patient care issues, management and interpersonal relationship problems and environmental and resource problems; the SCL-90 scale of somatization, obsessive symptoms, anxiety, depression, factor the number of positive items and total scores were higher than the national norm(P< 0.05);after intervention measures of nurses factor score was significantly lower than before intervention, the difference was statistically significant(P<0.05). Conclusions Neurology nurses have some mental problem. We should pay attention to the adjustment of coping style and mental state, to take corresponding measures,eliminate the work pressure source,in order to improve the quality of nursing care. Key words: Neurology; Nurse; Psychological health; Intervention

Anatomy and Physiology of Left Ventricular Suction Induced by Rotary Blood Pumps.

This study in five large greyhound dogs implanted with a VentrAssist left ventricular assist device focused on identification of the precise site and physiological changes induced by or underlying the complication of left ventricular suction. Pressure sensors were placed in left and right atria, proximal and distal left ventricle, and proximal aorta while dual perivascular and tubing ultrasonic flow meters measured blood flow in the aortic root and pump outlet cannula. When suction occurred, end-systolic pressure gradients between proximal and distal regions of the left ventricle on the order of 40-160 mm Hg indicated an occlusive process of variable intensity in the distal ventricle. A variable negative flow difference between end systole and end diastole (0.5-3.4 L/min) was observed. This was presumably mediated by variable apposition of the free and septal walls of the ventricle at the pump inlet cannula orifice which lasted approximately 100 ms. This apposition, by inducing an end-systolic flow deficit, terminated the suction process by relieving the imbalance between pump requirement and delivery from the right ventricle. Immediately preceding this event, however, unnaturally low end-systolic pressures occurred in the left atrium and proximal left ventricle which in four dogs lasted for 80-120 ms. In one dog, however, this collapse progressed to a new level and remained at approximately -5 mm Hg across four heart beats at which point suction was relieved by manual reduction in pump speed. Because these pressures were associated with a pulmonary capillary wedge pressure of -5 mm Hg as well, they indicate total collapse of the entire pulmonary venous system, left atrium, and left ventricle which persisted until pump flow requirement was relieved by reducing pump speed. We suggest that this collapse caused the whole vascular region from pulmonary capillaries to distal left ventricle to behave as a Starling resistance which further reduced right ventricular output thus contributing to a major reduction in pump flow. We contend that similar complications of manual speed control also occur in the human subject and remain a major unsolved problem in the clinical management of patients implanted with rotary blood pumps.

Patient management problem.

Patient management problem.

Today’s Cutting Edge In Research Education Increases Tomorrow’s Employability

Evidence-based medicine (EBM) is now considered a fundamental basis for clinical practices globally. There is an enormous necessity of going beyond merely reading research articles to actually applying research studies to solve patient management problems on a day to day basis. In order to have a cutting edge in a very competitive, international trade of education, Monash University Malaysia encourages Year 1 and 2 undergraduates to engage in various research projects, available within the School of Medicine during their semester breaks. This paper demonstrates a student’s use of experiential learning, reflective journaling and blended Learning while engaging in a research project. The basic research skills acquired early in the undergraduate MBBS curriculum is expected to achieve advance level research skills as the medical student completes the fifth year of the course. Hence, today’s cutting edge of developing research skills early increases the chances of tomorrow’s employability and employment in evidence based health care settings.

A New Threat in Anaesthesia-Bonzai.

To the Editor, Anaesthetists face problems in anaesthesia management of patients and have various preoperative problems in parallel with today’s changing conditions. Some of them are rare and some are common preoperative diseases. Another group includes cases realized because of changes in the patient’s clinical features. However, various drugs and herbal extracts taken by the patient without giving their medical history may leave us in an extremely difficult situation. In this paper, it was aimed to share the experience of a patient in whom ureterorenoscopy was planned for his urethral calculi. The patient was a 43-year-old male. His weight was 76 kg and height was 176 cm. He was taken to the operating room after receiving his written informed consent. There was no other feature apart from hypertension in his preoperative evaluation. He was receiving acetylsalicylic acid 100 mg and metoprolol succinate 50 mg tablets. The blood pressures were within the reference interval in his preoperative follow-ups. When he came to the operating room, his blood pressure was 210/126 mmHg and his heart rate was 86 pulses/min. Considering that he could have anxiety, the patient was sedated with midazolam and remifentanil hydrochloride. On being unable to lower the blood pressure, he was taken to the recovery room for follow-up. During the 2 h follow-up, he was given captopril 25 mg tablet. However, the blood pressure was still high. The problems that the he could face because of the situation were told him in detail. Thereupon, the patient mentioned that he was a drug addict and that he took Bonzai because he had a high stress the night before the operation. In view of this clinical picture of rising blood pressure, the operation was postponed until he became haemodynamically stable. As all of us watch the developments with anxiety, bonzai has become among the most important drug problems in our day. Bonzai is a semi-synthetic drug, obtained by adding various chemicals to some dried and shredded plants. It takes the name because the leaves of bonzai tree are generally used. The synthetic drug is known as Jamaican, Spice, Spice Gold, Spice silver, Yucatan Fire and K2 (1–3). Although there are not accurate data with respect to its prevalence, its use has increased because of its easy access and relatively low price. It is seen that synthetic cannabinoid, which is a content of Spice and Spice-like products, has just begun to be forbidden and kept under control in Austria and Germany (1, 2, 4). In our country, it was widely used, till it was added to the drug and stimulant list in the drug inspection law by the Decree of the Council of Ministers dated 07.01.2011 and numbered 2011/1310 (13.02.2011 dated and 27845 numbered official journal) (1). Although similar effects are seen with an excess of marijuana use, it is emphasized by researchers that bonzai is much more dangerous. One of the most important symptoms of it is its stimulant effect on the cardiovascular system (2–5). It causes sudden death because of a sudden and fast increase in blood pressure and a rise in the heart rate. There is some evidence indicating there is a correlation between synthetic cannabinoid use and acute renal failure (5). Moreover, it may lead to symptoms such as severe dryness of the mouth, eye redness, hallucination, convulsion and loss of consciousness (3, 4). To diagnose it is highly difficult unless the person himself reports or he is closely followed up (4). We realized with anxiety and worry in this patient that bonzai may be among the reasons in cases with hypertension of unknown origin. We aimed to share our experience.

Execution of Children with Dental Heebie-Jeebies by Alchemic Delusional Dissipation

Anxiety poses a significant problem in management of paediatric dental patients. Distraction can be an effective tool to manage these patients. The aim of this study was to evaluate efficacy of magic tricks distraction in management of anxiety. Forty children between 5 to 9 years of age, with no previous dental experience who required undergoing procedure needing application of local anaesthesia were included. They were divided into 2 groups – Group I-Control, Group II-Magic Distraction. Each child had 2 dental visits – 1.Screening followed by oral prophylaxis or restorative procedures without the need of a local anaesthetic injection. 2. Procedures necessitating need of a local anaesthetic injection. Control group received treatment without introduction of any distraction. Magic group viewed magic tricks videos. During each visit, the child’s anxiety levels were recorded: Before start of treatment, during treatment and posttreatment by using Venham’s Picture Test , Venham’s Anxiety Rating Scale, Pulse Rate, Oxygen Saturation. The mean range of Venham’s Picture Test Score, Venham’s Anxiety Rating and Pulse Rate was consistently lower for Group II patients across both visits. The Mean range for Oxygen Saturation was more for Group II than the control group.

Poly-Pharmacy Among the Elderly: Analyzing the Co-Morbidity of Hypertension and Diabetes

Clinical medicine faces many challenges, e.g. applying personalized medicine and genomics in daily practice; utilizing highly specialized diagnostic technologies; prescribing costly therapeutics. Today's population is aging and patients are diagnosed with more co-morbid conditions than in the past. Co-morbidity makes management of the elderly difficult also in terms of pharmacotherapy. The high prevalence of hypertension and diabetes as co-morbidities is indicative of the complexities that can impact accuracy in diagnosis and treatment, with poly-pharmacy being a significant component. It is essential to apply analytic methods to evaluate retrospective data to understand real world patients and medical practice. This study applies social network analysis, a novel method, to administrative data to evaluate the scope and impact of poly-pharmacy and reveal potential problems in management of elderly patients with diabetes and hypertension. Social Network Analysis (SNA) enables the examination of large patient data sets to identify complex relationships that may exist and go undetected either because of infrequent observation or complexity of the interactions. The application of SNA identifies critical aspects derived from over-connected portions of the network. These criticalities mainly involve the high rate of poly-pharmacy that results from the observation of additional co-morbid conditions in the study population. The analysis identifies crucial factors for consideration in developing clinical guidelines to deal with real-world patient observations. The analysis of routine health data, as analyzed using SNA, can be further compared with the inclusion/exclusion criteria presented in the current guidelines and can additionally provide the basis for further enhancement of such criteria.

Integration of Islamic Input in Medical Curriculum – Universiti Sains Islam Malaysia (USIM) Experience

Muslim doctors are those qualified doctors who practise their professional knowledge and skills in line with Islam and upholds the highest standards of ethical and professional behaviour. The medical curriculum of the Faculty of Medicine and Health Sciences of Universiti Sains Islam Malaysia (USIM) was designed with the integration of Islamic input which aims at producing doctors who are able to practise medicine that is integrated with Islamic, moral and ethical values. Halaqah Studies and Fundamental Islamic Knowledge (FIK) courses such as History of Medicine in Islam, Science and Medicine in Quran and Sunnah, Akhlak and Tasawuf, Islamic Jurisprudence and Medical Ethics and Fiqh Issues are taught to students during the pre-clinical and clinical phases. Memorization of selected Quranic verses throughout the programme aim to get the students to apply the verses of the al-Quran into practice in everyday life and especially in their clinical practice. Islamic values are emphasised during doctor-patient interactions in all clinical postings. Islamic knowledge and values integrated in the curriculum are assessed in written and clinical examinations. The outcome of the integration of the Naqli component in the medical curriculum has been demonstrated positively by the students in the patient management problems and clinical consultations. Studies on the outcome of the integrated Islamic input in the medical curriculum among the clinical students and graduates are being carried out.

Time to follow guidelines, protocols, and structured procedures in medical care and time to leap out.

Present medical practice encourages management according to written guidelines, protocols, and structured procedures (GPPs). Daily medical practice includes instances in which “leaping” from one patient management routine to another is a must. We define “frozen patient management”, when patient management leaping was required but was not performed. Frozen patient management may cause significant damage to patient safety and health and the treatment quality. This paper discusses the advantages and disadvantages of GPP-guided medical practice and gives an explanation of the problem of frozen patient management in light of quality engineering, control engineering, and learning processes. Our analysis of frozen patient management is based on consideration of medical care as a process. By considering medical care processes as a closed-loop control process, it is possible to explain why, when an indication for deviation from the expected occurs, it does not necessarily attract the medical teams’ attention, thereby preventing the realization that leaping to an alternative patient management is needed. We suggest that working according to GPPs intensifies the frozen patient management problem since working according to GPPs relates to “exploitation learning behavior”, while leaping to new patient management relates to “exploration learning behavior”. We indicate practice routines to be incorporated into GPP-guided medical care, to reduce frozen patient management.

Impedance Changes Indicate Proximal Ventriculoperitoneal Shunt Obstruction In Vitro.

Extracranial cerebrospinal fluid (CSF) shunt obstruction is one of the most important problems in hydrocephalus patient management. Despite ongoing research into better shunt design, robust and reliable detection of shunt malfunction remains elusive. The authors present a novel method of correlating degree of tissue ingrowth into ventricular CSF drainage catheters with internal electrical impedance. The impedance based sensor is able to continuously monitor shunt patency using intraluminal electrodes. Prototype obstruction sensors were fabricated for in-vitro analysis of cellular ingrowth into a shunt under static and dynamic flow conditions. Primary astrocyte cell lines and C6 glioma cells were allowed to proliferate up to 7days within a shunt catheter and the impedance waveform was observed. During cell ingrowth a significant change in the peak-to-peak voltage signal as well as the root-mean-square voltage level was observed, allowing the impedance sensor to potentially anticipate shunt malfunction long before it affects fluid drainage. Finite element modeling was employed to demonstrate that the electrical signal used to monitor tissue ingrowth is contained inside the catheter lumen and does not endanger tissue surrounding the shunt. These results may herald the development of "next generation" shunt technology that allows prediction of malfunction before it affects patient outcome.

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function.

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered.

Experience using of ultrasound guidance pleural tapping in pleural effusion after cardiac surgery in National Cardiac Centre Harapan Kita Hospital. Indonesia (Case Series)

Pleura effusion in post cardiac surgery is the one of problems in management of cardiac surgery patients. Large amounts of pleura effusion may affect the recovery period requiring a longer hospital stay. Early diagnosis and quantification of pleural effusion is important to be ideal postoperative adequate treatment. Ultrasound shows better sensitivity and reliability for diagnosis pleural effusion than physic diagnostic and X-ray. Ultrasound can be repeated serially at bedside without any radiation risk. Procedure perform under ultrasound guided showed a reduction of complication rate. We report 60 patients with pleural effusion after cardiac surgery. We perform tapping of fluid under guiding ultrasound. Before procedure we calculate amount of pleural effusion and make decision where site of needle will inserted. Regarding the literature we make intraclavicula line as a guided. Tapping procedure will perform if fluid more than 450 cc. Tapping procedure use abbocate needle no 14 or 16fr. Amount of perithoracosistesis fluid is almost same with fluid prediction of before +/- 50 cc, depend on body weight and size of heart if pleural effusion on left thorax. There are not complications after the procedure. Patient experiences were feel convenient and with minimal pain. After procedure patients can complete mobilization and if indication to discharge patients can discharge directly.

Lead tolerance capacity of clinical bacterial isolates and change in their antibiotic susceptibility pattern after exposure to a heavy metal

Introduction: Heavy metal pollutions of soil and wastewater are a significant environmental problem as they are not degraded or destroyed. Several metal resistance mechanisms have been identified which is responsible for alteration of normal cell physiology leading to development of drug resistance in microorganisms. Heavy metals used in industry and in household products are, along with antibiotics, creating a selective pressure in the environment that leads to the mutations in microorganisms. The present study was carried out to study the heavy metal lead tolerance by bacteria and change in antibiotic-sensitivity pattern after its exposure. Materials and Methods: 30 clinical isolates from various samples received in the Department of Microbiology, Government Medical College, Surat, were included in the study. To check the lead tolerance capacity, isolates were exposed to graded concentration of lead nitrate by plate dilution method, starting from 50 up to 1000 μg/ml strength. Antibiotic susceptibility was performed by the Kirby Bauer disc diffusion method. A change in antibiotic susceptibility pattern was studied before and after lead exposure. Result: 30 clinical isolates were included in the study, 25 Gram negative (83.3%) and 5 Gram positive (16.7%). MIC to lead was higher in Acinetobacter spp. and Pseudomonas spp. (600-1000 μg/ml) as compared to E. coli, Klebsiella spp., S. aureus (50-150 μg/ml). Multiple antibiotic resistance indexes were changed significantly after lead exposure. Conclusion: Bacteria exposed to high levels of heavy metals in their environment have adapted to this stress by developing various resistance mechanism. Infection with antibiotic-resistant organisms create problem in treatment and management of patients. We should take efforts to prevent environmental pollution with such heavy metals and transmission of antibiotic-resistant microorganism from environment to health care set up.

The haemodynamic cascade

The haemodynamic cascade

Spirituality and Religion in Pain and Pain Management.

Pain relief is a management problem for many patients, their families, and the medical professionals caring for them. Although everyone experiences pain to some degree, responses to it vary from one person to another. Recognizing and specifying someone else’s pain is clinically a well know challenge. Research on the biology and neurobiology of pain has given us a relationship between spirituality and pain. There is growing recognition that persistent pain is a complex and multidimensional experience stemming from the interrelations among biological, psychological, social, and spiritual factors. Patients with pain use a number of cognitive and behavioral strategies to cope with their pain, including religious/spiritual factors, such as prayers, and seeking spiritual support to manage their pain. This article provides an overview of the complex phenomenon of pain, with a focus on spiritual and religious issues in pain management.

Spirituality and religion in pain and pain management

Pain relief is a management problem for many patients, their families, and the medical professionals caring for them. Although everyone experiences pain to some degree, responses to it vary from one person to another. Recognizing and specifying someone else’s pain is clinically a well know challenge. Research on the biology and neurobiology of pain has given us a relationship between spirituality and pain. There is growing recognition that persistent pain is a complex and multidimensional experience stemming from the interrelations among biological, psychological, social, and spiritual factors. Patients with pain use a number of cognitive and behavioral strategies to cope with their pain, including religious/spiritual factors, such as prayers, and seeking spiritual support to manage their pain. This article provides an overview of the complex phenomenon of pain, with a focus on spiritual and religious issues in pain management.

Rituximab for the Treatment of Follicular Lymphoma

Rituximab is the first and most widely adopted anti-CD20 monoclonal antibody, and has dramatically improved outcomes for patients with B-cell malignancies. Rituximab is active as a single agent and when combined with chemotherapy improves both response rates and survival compared with chemotherapy alone. This approach has become standard of care in this setting. A number of Phase III studies using extended applications of rituximab have demonstrated that patients achieve a significantly longer progression-free survival, at the cost of an increase in infective complications. This has resulted in the widespread adoption of maintenance rituximab following the completion of primary therapy. Rituximab is useful in both previously untreated patients and at relapse, although a subset of patients develop disease that is rituximab resistant, which along with histologic transformation remains a significant management problem for patients with follicular lymphoma. The toxicities are modest and manageable, including infusion reactions, late-onset neutropenia, impaired humoral immunity, reactivation of hepatitis and possibly pulmonary toxicity.

The third wave in health sciences education

In 1980, the futurist, Alvin Toffler, published a book, The Third Wave, in which he described human history in terms of 3 waves; the first related to agriculture and accumulation of land mass, with lords and ladies owning vast tracts of land to be farmed by their serfs, the second, the industrial revolution, related to the accumulation of wealth through the efficient production of mass goods, leading to an aristocracy based on finance and resources—the Carnegies, Rockefellers, and Vanderbilts of late nineteenth century America, and, in 1971 still far in the future but now upon us, a third wave based on knowledge. Of course, the computer revolution, and the instant access to the world’s knowledge through Google, exemplifies the third wave. To write this editorial, I perused the table of contents of the next few issues, and discovered something I was only dimly aware of. We are seeing more and more papers related to the ‘‘science of learning’’ in the words of Richard Mayer, experimental research based on cognitive theories of the nature of human learning. Seven of the next 20 papers in the AHSE publication queue are in this tradition. In addition, many of the researchers who have developed this paradigm within mainstream psychology are now publishing a number of papers in health sciences—more on this later. We appear to be experiencing a parallel three wave evolution. I am not referring to the personae—that was covered in an article I wrote a few years ago (Norman 2011). Rather, I see a quiet, but dramatic shift occurring in the research paradigms we employ. The first was dominant when I entered the field. Its roots were in behaviorism, which specifically excluded mental processes from its purview. This ascetic paradigm reduced the world of learning to reinforcement of simple responses to simple stimuli. We created long lists of behavioral objectives, which implicitly reduced the graduating physician to an interminable checklist of behaviours (the resemblance to Competency Based Education is, I’m sure, just coincidental). We tested competence with multiple choice questions, with one right answer (some things don’t change) and ‘‘Patient Management Problems’’, where once again, the dialog between physician and patient was reduced to a long list of items to

THU0401 Audit of Atypical Hip Fractures at the Royal Berkshire Hospital

BackgroundThere is increasing evidence suggesting an association between bisphosphonate use and the occurrence of atypical femoral fractures1,2. The incidence of atypical femoral fractures accounts for less than 1% of hip...