Individual variability of neural computations in the primate retina.

Variation in the neural code contributes to making each individual unique. We probed neural code variation using ∼100 population recordings from major ganglion cell types in the macaque retina, combined with an interpretable computational representation of individual variability. This representation captured variation and covariation in properties such as nonlinearity, temporal dynamics, and spatial receptive field size and preserved invariances such as asymmetries between On and Off cells. The covariation of response properties in different cell types was associated with the proximity of lamination of their synaptic input. Surprisingly, male retinas exhibited higher firing rates and faster temporal integration than female retinas. Exploiting data from previously recorded retinas enabled efficient characterization of a new macaque retina, and of a human retina. Simulations indicated that combining a large dataset of retinal recordings with behavioral feedback could reveal the neural code in a living human and thus improve vision restoration with retinal implants.

Open communication between caregivers' and terminally ill cancer patients about illness and death: The role of gender - A correlational study.

PURPOSE: Caregivers face severe difficulties in communicating openly with their terminally ill relatives about illness and death. Some studies suggest that females are more likely than males to hold such conversations. We compared level of open communication between male and female spouse-caregivers, and the contribution of personal and situational characteristics to the explanation of open communication level within each gender group. METHODS: The study design was correlational. We interviewed 77 spousal-primary caregivers of terminal cancer patients. Participants were recruited over a 10-month period from the home hospice unit of the central region of Israel's largest Health Maintenance Organization. The questionnaire included measures of open communication, along with caregiver's personal and situational characteristics. RESULTS: Female spouses reported higher levels of open communication about illness and death with their loved ones, compared to male spouses. Among males, duration of care and self-efficacy emerged as significant contributors to open communication level. Among females, self-efficacy and ethnic origin were found to be significant explanatory variables. CONCLUSIONS: This study demonstrates the important role gender plays in level of open communication between spousal caregivers and terminal cancer patients, concerning their illness and approaching death. Self-efficacy, ethnic origin and duration of care are also significant factors explaining open communication of both male and female caregivers. These factors should be considered by nurses and other healthcare professionals when developing intervention programs to increase the level of open communication between family caregivers and their terminally ill relatives.

Evaluating the Need for Palliative Care Services at a General Hospital in Israel.

BACKGROUND: Most hospitals in Israel do not provide palliative care beds and only few general hospitals have palliative consultation services. To date there are no data on the rate of hospitalizations and the need for palliative care in general hospitals in Israel. OBJECTIVE: The objective was to characterize patients in need of palliative treatment during hospitalization in a general hospital in Israel. METHODS: A retrospective review was performed of a random sample of files of patients admitted to the Internal Medicine Department at the Soroka University Medical Center (SUMC) between May 2007 and April 2008. Patients were defined as in need of palliative care if they had a CARING score ≥13. The data were collected using a structured questionnaire that included sociodemographic data and data on comorbid conditions, main complaints, primary diagnosis, duration of hospitalization, and hospitalization outcome. RESULTS: We reviewed 2795 hospitalizations. Of these, 14.9% were defined as in need of palliative care. Fourteen percent of the patients died during hospitalization and 47% died over the six-month follow-up period. The most common primary diagnosis was malignancy (61%), followed by end-stage pulmonary disease (19%) and Alzheimer's and other causes of dementia (9%). In only 12 hospitalizations (3.5%) was palliative care arranged for patients at discharge. CONCLUSIONS: A high percentage of patients hospitalized in internal medicine divisions could benefit from palliative care. The data presented here could aid hospitals in the integration of palliative care services.

[Dealing with violence in primary care].

This case report discusses how the family doctor and the clinic staff deal with a violent mistrusting patient. Are doctors obliged to treat violent patients? What are the limits of such treatment relationship? What might be their implications? The debate relates to ethical guidelines and initial reports about termination of treatment relations initiated by family doctors in southern Israel.

Prevalence and management of symptoms during the last month of life.

BACKGROUND: The prevalence and severity of the "most troublesome" symptoms in terminally ill patients are well known and have been studied in many settings. However, these symptoms change during the course of advanced disease. OBJECTIVES: To evaluate the range and trajectory of symptoms in the final stage of life as measured a month prior to death. METHODS: Patients with an expected prognosis of less than 6 months were recruited forthe study. Excluded were non-Hebrew or Russian speakers, and patients with cognitive impairment or a diagnosis of brain tumor. A structured questionnaire was used to interview patients and their caregivers at home every 2 weeks until death. We present a comparison analysis of 45 patients who completed both interviews 2 and 4 weeks before death. RESULTS: There were five symptoms (fatigue, pain, reduced wellbeing, lack of appetite, somnolence) that were reported most frequently, occurring in more than 70% of the patients. Most of the symptoms showed a worsening trend towards death. CONCLUSIONS: Assessing the presence and severity of symptoms as a guide to start or modify treatment is recommended. Knowledge of how symptoms change in the final stage of life could better assist in the management of resources and could help patients and their families in their final preparations.

Opioid use in an Israeli health maintenance organization: 2000-2006.

OBJECTIVE: The objective of this study was to assess opioid use during 7 years (2000-2006) among Clalit Health Services (CHS) members. DESIGN: Purchasing data of opioids authorized for use in Israel were obtained from the computerized databases of CHS. Patient demographics and cancer morbidity were also extracted. The data were analyzed by converting the purchased opioids to oral morphine equivalents (OMEs). SETTING: CHS is the largest health maintenance organization in Israel (3,774,600) and insures almost 54% of the Israeli population. PATIENTS: All CHS members who purchased an opioid at least once during the 7-year study period (2000-2006). INTERVENTION: There were no interventions in this study. OUTCOME MEASURES: The outcome measures of this study were total OME purchased per year, OME (mg) per capita/per year, and OME (mg) daily dose. RESULTS: There were 119,562 patients who purchased an opioid at least once (3.2% of CHS population). Of them, 57.4% were women, 69.0% aged 65 years and above (average age 56.05 years +/- 26.7), 7.7% purchased opioids for more than 12 months, and 81.3% purchased opioids for only 1-4 months. A 96% increase in total OME purchased was found between 2000 and 2006 (from 56.4 kg to 110.6 kg). The annual OME purchased per capita increased from 15.7 mg in the year 2000 to 29.3 mg in 2006. The total number of patients who received at least one opioid prescription increased by 60%, while the growth in total number of CHS members was smaller (4.8%). CONCLUSIONS: There is a growing use of opioids at CHS during the 7-year period, a potential indicator of the progress made in improving accessibility and availability of opioids in our health care organization in Israel.

Providing culturally sensitive palliative care in the desert-the experience, the need, the challenges, and the solution.

The Bedouin population of the Negev region in Israel consists of 180,000 Muslims, half of whom live in six townships. The other half is dispersed in small temporary settlements (huts, tents) with no running water or electricity. Accessibility is quite difficult, with no paved roads or any form of motorized public transportation. For patients with advanced illnesses near the end of life, adequate palliative treatment is not available in their rural homestead. A mobile palliative care unit (MPCU) has been established, with the aims of delivering palliative care to terminal patients living in remote regions not easily accessible to the community health care teams and to provide palliative care consultation services to the local primary care teams. The mobile unit consists of a core team of a nurse, a social worker, a physician, and a Bedouin driver-interpreter/translator. The MPCU cares for about 30 patients at any given time, including four to six Bedouins living in rural homesteads, four to six Bedouins living in townships, and the remainder Jewish patients living in the surrounding settlements. One hundred patients were cared for and about 1800 home visits were conducted during the past year, including 15% by the whole mobile unit team, 15% by the physician alone, 25% by the nurse alone, and 25% by the unit's nurse together with the local primary clinic nurse. The average distance covered per home visit was around 70km. Our experience in establishing a culturally sensitive MPCU can be a model to provide palliative care services in remote areas.

Teaching end-of-life care to family medicine residents--what do they learn?

BACKGROUND: In order to address adequately basic palliative care issues, post graduate teaching programs for physicians should provide, in addition to basic knowledge in the field and clinical skills, also training in terms of orientations and skills which enable physicians to overcome their emotional difficulties as well as professional barriers. This paper presents a model of teaching and its evaluation. AIMS: The purpose of this project was to develop an educational program for residents in family medicine and evaluate its effect over time. The focus was on the self-perceived ability of physicians for understanding and communicating with terminally ill patients; the physicians' ability to deal with their own emotional difficulties while caring for the terminally ill; and the physicians' confidence regarding the management of over-all suffering. METHODS: Structured questionnaires were filled out by 21 physicians before and after an 8 months program of residency training in palliative care. RESULTS: Factor analysis yielded three factors: (A) Beliefs focusing on the resident's ability to understand terminally-ill patients and to communicate with them, (B) Beliefs regarding the effect of the program on the resident, and (C) Beliefs about self-professional skills. A comparison with the responses at the end of the program indicated a trend towards increased communication capabilities, relating increased importance to the program and a significant improvement in self confidence in professional skills. CONCLUSIONS: The results of the evaluation indicate that this teaching program has achieved its goals by not only improving the physician's knowledge, but also causing a positive change in attitudes regarding end-of-life care. Considering our positive results it is recommended to incorporate similar training programs in physicians' post-graduate studies.

Chronic pain: a population-based study.

BACKGROUND: The prevalence of chronic pain in the general population ranges from 10% to over 40%, depending on the definition and the population studied. No large study has been conducted in Israel. OBJECTIVES: To evaluate the prevalence of patients with chronic pain, and characterize them in a large community random sample. METHODS: We conducted a survey of Clalit Health Services members, interviewing them by phone. A random sample of 4063 Clalit members, 25 years or older and Hebrew speakers, were screened for chronic pain, defined as: any pain or discomfort that in the last 6 months has persisted continuously or intermittently for more than 3 months. RESULTS: Eight percent (n=325) refused to participate. Of the 3738 included in the study, 1722 (46%) reported chronic pain in at least one site. Most of the patients were over 50-years-old (62%) (mean age 56 +/- 16, range 27-97 years). Women suffered significantly more than men, as did those who were older, less educated and born in Israel and Eastern Europe. Prevalent painful sites were the back (32%), limbs (17%) and head (13%). More than a third reported severe pain and impaired life activities. Only 4.8% of the patients suffering from chronic pain were referred to pain specialists and 11% used complementary medicine. A logistic regression model showed that women and patients with a low education level were the only significant variables predicting higher life impact index and higher pain severity. CONCLUSIONS: We found a high prevalence of chronic pain in the study population. Chronic pain causes severe disturbance to quality of life. A low rate of referral to pain specialists and complementary medicine was observed.

Taking care of terminally-ill patients at home - the economic perspective revisited.

End-of-life care can be delivered in a variety of settings, whereby the majority of terminally-ill cancer patients prefer to die at home. The aim of our study is to evaluate health services utilisation during the last year of life, and to compare terminally ill patients who have received home-specialised palliative care services (HSPCS) with patients who died receiving home non-specialised palliative care services. The study included 120 and 515 patients, respectively, who died between 1999-2000. Age and gender distribution were similar in both groups. During the last year of life, mean health services cost per person among the HSPCS group was lower by more then 30% (P < 0.005). The median cost per patient was as low as one-fifth in the last month. Men and the older age group of 65 and above, cost significantly less compared with women and younger patients, respectively, regardless of provider setting. The main differences in health services utilisation were in hospitalisations and oncology treatments (P < 0.01 and P < 0.05, respectively).

[Trend in opioids use for chronic pain treatment at Clalit Health Services (2000-2004)].

BACKGROUND: Opioids are considered a cornerstone in the treatment of cancer and non-cancer pain. The World Health Organization considers a country's morphine consumption to be an important indicator of the quality of pain control. There is little or no use of opioids in nearly half of the countries in the world. OBJECTIVE: To assess the change in trends of opioids use for chronic pain treatment over a period of five years (2000-2004) among members of Clalit Health Services (CHS) in Israel. METHOD: Data on the consumption of opioid analgesic drugs that were authorized for use in Israel during the years 2000-2004 were obtained from the computerized data bases of CHS. In addition, patient's demographic details and cancer morbidity were also extracted. To make the patient's use of opioids comparable, we analyzed the data by translating all opioids consumption (fentanyl patch, oxycodone, methadone, hydromorphone) to oral morphine equivalents. RESULTS: An increase of 68% in total morphine consumption was found between the years 2000 and 2004 (from 56.4 Kg to 94.9 Kg) and in mg morphine per prescription from 15.7 to 25.3 mg. The total amount of morphine per prescription increased from 834.2 mg to 892.9 mg. The total number of patients who received an opioid prescription multiplied by 1.47 (from 18,551 to 27,302) while the growth in total number of CHS members was significantly smaller. No significant differences were found during the years in the characteristics of patients who received opioids; regarding gender (58% were woman) and age (about 80% were 65 years old and above). During the year 2004, a preliminary examination of opioids consumption, comparing cancer and non-cancer pain patients, showed that cancer pain patients used 2.74 times higher dosage than non-cancer pain patients (6110.8 vs. 2225.6 mg/patients/year). CONCLUSIONS: During the 5 year period evaluated, there is a growing trend in use of opioids at CHS in Israel. This trend may be an indication of the improvement in treatment of chronic pain.

Home death--the caregivers' experiences.

The objectives of this study were to evaluate caregivers' experiences concerning the care of a terminally ill loved one at home, and to compare the death experiences of caregivers with and without access to homecare programs. The primary caregivers of all the patients who died of cancer 6-18 months before the study period (1999-2001) in the Negev area were contacted. This group included 240 caregivers of patients who died in the home palliative care program and 404 caregivers of patients who died with no access to a home palliative care program. A total of 159 caregivers were interviewed, 76 from the home palliative program and 83 who had no access to a palliative care program. Death at home occurred for 80.3% of patients with access to homecare and 20.5% of those without access. Despite the fact that caring for a loved one at home was a greater financial and emotional burden, there was a greater overall satisfaction with the caring experience of those whose loved ones died at home and had access to the homecare program. Given appropriate professional support systems, home-based care at the end of life is preferable to most caregivers.

Spikernels: predicting arm movements by embedding population spike rate patterns in inner-product spaces.

Inner-product operators, often referred to as kernels in statistical learning, define a mapping from some input space into a feature space. The focus of this letter is the construction of biologically motivated kernels for cortical activities. The kernels we derive, termed Spikernels, map spike count sequences into an abstract vector space in which we can perform various prediction tasks. We discuss in detail the derivation of Spikernels and describe an efficient algorithm for computing their value on any two sequences of neural population spike counts. We demonstrate the merits of our modeling approach by comparing the Spikernel to various standard kernels in the task of predicting hand movement velocities from cortical recordings. All of the kernels that we tested in our experiments outperform the standard scalar product used in linear regression, with the Spikernel consistently achieving the best performance.

Online ranking by projecting.

We discuss the problem of ranking instances. In our framework, each instance is associated with a rank or a rating, which is an integer in 1 to k. Our goal is to find a rank-prediction rule that assigns each instance a rank that is as close as possible to the instance's true rank. We discuss a group of closely related online algorithms, analyze their performance in the mistake-bound model, and prove their correctness. We describe two sets of experiments, with synthetic data and with the EachMovie data set for collaborative filtering. In the experiments we performed, our algorithms outperform online algorithms for regression and classification applied to ranking.

Pain control in ambulatory cancer patients--can we do better?

To evaluate the degree of pain control among ambulatory cancer patients visiting the outpatient clinics of three oncology centers in south Israel, these patients were interviewed using the Brief Pain Inventory translated into Hebrew (BPI-Heb). Patients suffering from pain at least three times a week or reporting taking daily analgesics during the last two weeks were enrolled. Non-Hebrew speakers and patients too frail or ill were excluded. The study population included 218 subjects. Substantial pain was experienced by 77%, the majority was not adequately treated (81%), and 75% were undermedicated. The daily living activities of the majority of patients (64%) were moderately to severely impacted. Pain control was not associated with any of the sociodemographic or previous treatment profile variables, or by physicians' pain assessment. The physicians' and the patients' ratings of the extent to which pain interfered with the patients' activities fully agreed (+/-2) in fewer than half of the patients. Physicians estimated more severe pain levels, but underestimated its impact on everyday life. These data indicate that better pain control for ambulatory cancer patients is needed and that more information about patients' pain and its impact should be solicited. Further training of care providers is needed to improve the relief from cancer pain and the quality of life of patients.

Protein family classification using sparse markov transducers.

We present a method for classifying proteins into families based on short subsequences of amino acids using a new probabilistic model called sparse Markov transducers (SMT). We classify a protein by estimating probability distributions over subsequences of amino acids from the protein. Sparse Markov transducers, similar to probabilistic suffix trees, estimate a probability distribution conditioned on an input sequence. SMTs generalize probabilistic suffix trees by allowing for wild-cards in the conditioning sequences. Since substitutions of amino acids are common in protein families, incorporating wild-cards into the model significantly improves classification performance. We present two models for building protein family classifiers using SMTs. As protein databases become larger, data driven learning algorithms for probabilistic models such as SMTs will require vast amounts of memory. We therefore describe and use efficient data structures to improve the memory usage of SMTs. We evaluate SMTs by building protein family classifiers using the Pfam and SCOP databases and compare our results to previously published results and state-of-the-art protein homology detection methods. SMTs outperform previous probabilistic suffix tree methods and under certain conditions perform comparably to state-of-the-art protein homology methods.

Using substitution matrices to estimate probability distributions for biological sequences.

Accurately estimating probabilities from observations is important for probabilistic-based approaches to problems in computational biology. In this paper we present a biologically-motivated method for estimating probability distributions over discrete alphabets from observations using a mixture model of common ancestors. The method is an extension of substitution matrix-based probability estimation methods. In contrast to previous such methods, our method has a simple Bayesian interpretation and has the advantage over Dirichlet mixtures that it is both effective and simple to compute for large alphabets. The method is applied to estimate amino acid probabilities based on observed counts in an alignment and is shown to perform comparably to previous methods. The method is also applied to estimate probability distributions over protein families and improves protein classification accuracy.