Oncologists' identification of mental health distress in cancer patients: Strategies and barriers.

The purpose of this research was to examine oncologists' perspectives on indicators of mental health distress in patients: what strategies they use to identify these indicators, and what barriers they face in this task. Twenty-three oncologists were interviewed, and the grounded theory method of data collection and analysis was used. Oncologists perceived distress to be a normative part of having cancer and looked for affective, physical, verbal and behavioural indicators using a number of strategies. Barriers to identification of mental health distress included difficulty in differentiating between mental health distress and symptoms of the disease, and lack of training. A systematic, time-efficient assessment of symptoms of emotional distress is critical for identification of psychiatric disorders among patients and differentiating normative emotional responses from psychopathology. Clinical bias and misdiagnosis can be a consequence of an ad hoc, intuitive approach to assessment, which can have consequences for patients and their families. Once elevated risk is identified for mental health distress, the patient can be referred to specialised care that can offer evidence-based treatments.

Primary Care Provider Management of Congenital Hypothyroidism Identified Through Newborn Screening.

OBJECTIVE: To assess Primary Congenital Hypothyroidism (CH) management patterns and feasibility of providing long-term care for patients with CH identified through newborn screening by Primary Care Providers (PCPs) in California and Hawaii. STUDY DESIGN: A survey was mailed to all physicians (N=823) listed as the referral doctor for confirmed patients with CH identified through newborn screening programs in both states between 01/01/2009-12/31/2013. Information was collected on CH management patterns, barriers to providing care, and knowledge on CH treatment. Descriptive statistics and bivariate logistic regression results were reported. RESULTS: 206 PCPs completed the survey. Among these, 78% currently have patients with CH and 91% indicated willingness to provide long-term care to new patients with CH. Among PCPs currently caring for patients with CH, 17% managed CH by themselves with limited assistance from endocrinologists; 63% were involved in managing CH but endocrinologists played a larger role than PCPs; 19% were not involved in CH care. Only 49% of PCPs correctly answered questions regarding recommended follow-up frequencies and 23% knew the correct age for a trial off levothyroxine for suspected transient CH. Top two perceived barriers to providing long-term care included "need guidance or support from endocrinologists" (61%) and "not familiar with CH treatment guidelines" (28%). CONCLUSION: The majority of PCPs surveyed are willing to provide long-term care to patients with CH, but need support from endocrinologists and increased knowledge about current treatment guidelines.

Ambulatory physical activity during the initial training phase in a Naval Commando Unit.

BACKGROUND: There is a positive correlation between the volume of physical activity performed and the incidence of lower extremity overuse injuries. Difficulty in evaluating the amount of activity in which highly specialised military units are engaged has prevented the implementation of a strict training programme designed to minimise overuse injuries. PURPOSE: To quantify the ambulatory physical activity performed by trainees during the initial training phase in a Naval Commando Unit, with a view to developing more exact physical performance guidelines for the unit and the Israel Defense Forces, in general. METHODS: Twenty-four accelerometers were worn by two teams each day. Trainees were instructed to wear the device on their non-dominant wrist 24 h a day, during all types of activities. Twice a week, the devices were collected, checked for damage and recharged, and the data were transferred to a computer. RESULTS: Six trainees failed to complete the 9-week training period. Of the total 1512 accelerometer-days, 1075 readings (71%) were included in the study data. Trainees ambulated on average a distance of 15.5±8.61 km/day and 95.5 km/week. Accelerometer readings (estimated distances) were averaged each week for the two teams. The total distance measured over the 9-week study period was 911.15 km in team A and 808.38 km in team B. The total distance measured in both teams was, thus, almost double the planned 440 km (p=0.001). CONCLUSIONS: Trainees greatly exceeded the planned safe distance. High variability was observed between trainees from the same team.

Peptides for diagnosis and treatment of colorectal cancer.

Colorectal cancer (CRC) is a major health concern worldwide, as it is the third most frequently diagnosed cancer and the second leading cause of cancer-related death. There are a number of treatment options for CRC, however many of them are disappointing. Therefore, significant efforts are directed towards the development of new biological therapies with improved efficacy. The use of peptides in CRC treatment holds promise as emerging novel anti-cancer agents. Targeted therapy based on the use of peptides that can directly target tumor cells without affecting normal cells is evolving as an alternative strategy to conventional therapies and particularly, chemotherapy. The main advantages of peptides are their relatively easy and rapid synthesis process, and the vast possibilities for chemical modifications that can be exploited for novel peptide design and improved delivery. Peptides can be utilized directly as cytotoxic agents or indirectly as they can act as carriers of cytotoxic agents, drugs, or radioisotopes by specifically targeting tumor cells. They can also be used for diagnostic purposes. Current research focuses on developing peptides that can serve as tumor targeting moieties, permeabilize membranes to induce cytotoxicy, radiolabeled peptides, and peptide vaccines. In addition, improving targeting to tumors, reducing side effects, due to non-specific toxicity, and unraveling the pharmacokinetic characteristics of potential peptides, for either therapeutic or diagnostic use, are also subjects of intensive investigation. This review provides a brief overview on the role of peptides in CRC diagnosis and therapy that are currently being investigated, and their potential applications in the clinical setting.

Gene therapy of pancreatic cancer targeting the K-Ras oncogene.

Ras mutations are present in ∼95% of pancreatic cancer (PC) cases leading to increased proliferation and apoptosis resistance. The aim of this study is to selectively kill Ras-transformed cells by overexpressing the pro-apoptotic protein, p53 upregulated modulator of apoptosis (PUMA) under a Ras-responsive promoter. Colo357, Panc1 and MiaPaca, PC cell lines harboring K-Ras mutations, normal rat IEC18 enterocytes, and their K-Ras transformed R1 counterparts, were tested. We constructed adenoviral vectors containing the PUMA gene downstream to: (1) Four or five repetitive Ras-responsive elements (Ad-PY4/PY5-PUMA) and (2) a negative control (Ad-SV40-PUMA). Cell viability was estimated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and apoptosis was evaluated by FACS. In vivo potency of the adenoviruses was evaluated in athymic nude mice. Infection with Ad-PY4/PY5-PUMA markedly inhibited cell growth (∼40-50%), and apoptosis was detected in all cells with high Ras activity, whereas IEC18 cells remained unaffected. The control vector, Ad-SV40-PUMA, did not induce any cell death. Selective and high expression of PUMA was detected in Ad-PY4-PUMA-infected cells. In vivo, Ad-PY4-PUMA inhibited by ∼35% the growth of established tumors compared with the Ad-SV40-PUMA. Selective overexpression of PUMA efficiently inhibits the growth of Ras-transformed cells while sparing the normal ones. This treatment modality may become a useful, effective and safe approach to selectively target Ras-mutated tumor cells.

Improving implementation of infection control guidelines to reduce nosocomial infection rates: pioneering the report card.

BACKGROUND: Two detailed checklists were developed, based on published infection control guidelines, for daily use by infection control practitioners in departments and operating rooms. AIM: To assess the impact of the checklists on nosocomial infection rates in three hospitals over the course of one year. METHODS: The checklists included 20 subheadings (± 150 items). Project nurses conducted rounds in the study (but not control) departments; during each round, the nurses selected 15-20 items for observation, marked the checklists according to appropriateness of observed behaviour and provided on-the-spot corrective education. Rates of adherence to the checklist, antibiotic use, number of obtained and positive cultures, and positive staff hand and patient environment cultures were reported monthly as a report card to relevant personnel and administrators. The rate of nosocomial infections was determined in the first and last months. RESULTS: The baseline nosocomial infection rate was similar in the study and control departments: 37/345 (11%) and 26/270 (10%) respectively. In the last month, the rate in the study department decreased to 16/383 (4%) (P<0.01); in the control it decreased insignificantly to 21/248 (8%) (not significant). No significant trends were detected in the number of obtained cultures, positive cultures, or antibiotic use. Adherence to guidelines ranged from 75% to 94% between the hospitals (P<0.001): the overall rate increased from 80% to 91% (P<0.01). CONCLUSIONS: The use of checklists during the conduct of infection control rounds, combined with monthly reports, was associated with a significant decrease in nosocomial infections in study departments.

Quetiapine-associated cholestasis causing lipoprotein-X and pseudohyponatraemia.

A case of intrahepatic cholestasis secondary to treatment with quetiapine in combination with lamotrigine and zopiclone, resulting in severe hypercholesterolaemia without overt lactescence of the plasma, is presented. Abundant lipoprotein-X was seen on lipoprotein electrophoresis. The patient was diagnosed and treated for hyponatraemia which was likely factitious and caused by hypercholesterolaemia. Cholestasis and hypercholesterolaemia resolved over a period of several months after the discontinuation of quetiapine.

Eight years experience with enzyme replacement therapy in two children and one adult with Pompe disease.

Pompe disease (type 2 glycogenosis, acid maltase deficiency) is a disorder affecting skeletal and cardiac muscle, caused by deficiency of acid alpha-glucosidase. In 2006 enzyme therapy with recombinant human alpha-glucosidase received marketing approval based on studies in infants. Results in older children and adults are awaited. Earlier we reported on the 3-year follow-up data of enzyme therapy in two adolescents and one adult. In the present study these patients were followed for another 5 years. Two severely affected patients, wheelchair and ventilator dependent, who had shown stabilization of pulmonary and muscle function in the first 3 years, maintained this stabilization over the 5-year extension period. In addition patients became more independent in daily life activities and quality of life improved. The third moderately affected patient had shown a remarkable improvement in muscle strength and regained the ability to walk over the first period. He showed further improvement of strength and reached normal values for age during the extension phase. The results indicate that both long-term follow-up and timing of treatment are important topics for future studies.

The use of a perinatal internet consultation forum in Israel.

To analyse the use of a free, public, perinatal internet consultation service, 2000 consultations provided by university hospital staff were evaluated over 30 months. Ninety five percent of the questioners were women, and 62% of them were primiparous. The average response rate was 2.3 audience responses per question. Fifty-two percent of the consultations were related to labour and delivery, 23% were related to pregnancy complications, 16% were related to prenatal diagnosis, and 7% were related to the puerperium period. We conclude that medical consultation forums provide an additional way of delivering inexpensive, accessible, fast, and convenient healthcare services.

The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways.

Neurofibromatosis type 1 (NF1) is characterized by a high incidence of benign and malignant tumors attributed to loss of function of Nf1, which encodes neurofibromin, a tumor suppressor with Ras-GAP activity. Neurofibromin deficiency typically causes chronic activation of Ras, considered the major contributor to manifestation of NF1. Resistance to radio- and chemotherapy are typical of NF1-associated tumors, but the underlying mechanism is unknown. Here, we investigated interrelationships between neurofibromin expression, Ras activity, and sensitivity to apoptosis. Neurofibromin-deficient mouse embryonic fibroblasts (MEFs) and human NF1 tumor cells were more resistant than neurofibromin-expressing cells to apoptosis. Moreover, Nf1(-/-), Nf1(+/-), and Nf1(+/+) MEFs exhibited gene-dosage-related resistance to apoptosis. Resistance of the Nf1-deficient cells was mediated by two survival pathways: a Ras-dependent pathway, and a Ras-independent pathway promoted by the lack of an NF1-GRD-independent proapoptotic action of neurofibromin. Therefore, besides its Ras-dependent growth inhibition, neurofibromin can exert tumor suppression via a proapoptotic effect.

Mortality in terrorist attacks: a unique modal of temporal death distribution.

BACKGROUND: Terror-related multiple casualty incidents (MCI) in Israel since September 2000 have resulted in a new pattern of injury as a result of the mechanisms of trauma. The objective of this study was to asses the temporal death distribution among the civilian casualties in the Jerusalem vicinity during a 3-year period. METHODS: All terrorist attacks in the Jerusalem district from September 2000 to September 2003 were included in this study. The data of all deaths were processed including the time of the attack, the evacuation time to the hospitals, and the time of death. RESULTS: During the study period 28 terror-related MCI occurred. A total of 2328 victims were injured and 273 died, for an overall fatality rate of 11.7%. A unique temporal death distribution was identified; 82.8% of the deaths occurred immediately, at the scene of the attack (scene death); of the remaining 17.2% of patients who died in the hospital, half died within 4 hours of arrival (immediate death), one quarter within 5-24 hours (early death), and one quarter later than that (late death). The temporal death distribution was significantly different when classifying the mechanism of trauma to suicide bombings versus shooting. The scene mortality was higher in the suicide bombings than in shooting attacks (86.7% versus 77%, P = 0.039 ). In contrast, the mortality within 1-24 hours was higher in the shooting attacks (17% versus 6.3%, P = 0.05). CONCLUSIONS: Terror-related MCI occurring in civilian settings have a unique temporal death distribution. A very high scene mortality is seen compared to the classical description of Donald Trunkey1 in 1983. The late deaths, which composed 30% of the mortality in civilian settings, comprise only 4.4% of the total mortality in MCIs. A rough estimate of the in-hospital mortality could be achieved after the first 4 hours, allowing the assessment and distribution of hospital resources. Futile care should be identified early and availability of ICU beds can be calculated according to the immediate mortality.

Patterns of injury in hospitalized terrorist victims.

Acts of terror increase the demand for acute care. This article describes the pattern of injury of terror victims hospitalized at 9 acute-care hospitals in Israel during a 15-month period of terrorism. To characterize patients hospitalized as a result of terror injuries, we compared terror casualties with other injuries regarding severity, outcome, and service utilization. Using data from the National Trauma Registry, characteristics of casualties are portrayed. During the study period, 23,048 patients were recorded, 561 of them (2.4%) were injured through terrorist acts. Seventy percent were younger than 29 years. Seventy-five percent were males. Thirteen percent of terror victims compared with 3% with other traumatic injuries, arrived by helicopter. Injury mechanism consisted mainly of explosions (n = 269, 48%) and gunshot injuries (n = 266, 47%). One third of the population experienced severe trauma (Injury Severity Score > or = 16). One hundred-forty-two patients (26%) needed to be admitted to the intensive-care unit. Inpatient mortality was 6% (n = 35). Fifty-five percent of the injuries (n = 306) included open wounds and 31% (n = 172) involved internal injuries; 39% (n = 221) sustained fractures. Half of the patients had a procedure in the operating room (n = 298). Duration of hospitalization was longer than 2 weeks for nearly 20% of the population. Injuries from terrorist acts are severe and impose a burden on the healthcare system. Further studies of the special injury pattern associated with terror are necessary to enhance secondary management and tertiary prevention when occurring.

Suppression of NF-kappaB activation by infection with Toxoplasma gondii.

The interaction of host cells with microbial products or their invasion by pathogens frequently results in activation of the NF-kappaB family of transcription factors. The studies presented here reveal that in vivo, infection with Toxoplasma gondii results in the activation of NF-kappaB. To determine whether host cells could activate NF-kappaB in response to invasion by T. gondii, Western blots, immunofluorescence, and electrophoretic mobility shift assays were used to assess the response of host cells to infection. In these studies, infection of macrophages or fibroblasts with T. gondii did not result in the activation of NF-kappaB. In addition, the ability of lipopolysaccharide to activate NF-kappaB was impaired in cultures of macrophages infected with T. gondii. Together, these data demonstrate that invasion of cells by T. gondii does not lead to the activation of NF-kappaB and suggest that the parasite may actively interfere with the pathways that lead to NF-kappaB activation.

Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome.

PURPOSE: Clinical features associated with chromosome 1p36 deletion include characteristic craniofacial abnormalities, mental retardation, and epilepsy. The presence and severity of specific phenotypic features are likely to be correlated with loss of a distinct complement of genes in each patient. We hypothesize that hemizygous deletion of one, or a few, critical gene(s) controlling neuronal excitability is associated with the epilepsy phenotype. Because ion channels are important determinants of seizure susceptibility and the voltage-gated K(+) channel beta-subunit gene, KCNAB2, has been localized to 1p36, we propose that deletion of this gene may be associated with the epilepsy phenotype. METHODS: Twenty-four patients were evaluated by fluorescence in situ hybridization with a probe containing KCNAB2. Clinical details were obtained by neurologic examination and EEG. RESULTS: Nine patients are deleted for the KCNAB2 locus, and eight (89%) of these have epilepsy or epileptiform activity on EEG. The majority of patients have a severe seizure phenotype, including infantile spasms. In contrast, of those not deleted for KCNAB2, only 27% have chronic seizures, and none had infantile spasms. CONCLUSIONS: Lack of the beta subunit would be predicted to reduce K(+) channel-mediated membrane repolarization and increase neuronal excitability, suggesting a possible relation between loss of this gene and the development of seizures. Because some patients with seizures were not deleted for KCNAB2, there may be additional genes within 1p36 that contribute to epilepsy in this syndrome. Hemizygosity of this gene in a majority of monosomy 1p36 syndrome patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a significant risk factor for epilepsy.

[Trauma registry and injury].

The trauma registry network constitutes an essential database in every injury prevention system. In order to rationally estimate the extent of injury in general, and injuries from traffic accidents in particular, the trauma registry systems should contain the most comprehensive and broad database possible, in line with the operational definitions. Ideally, the base of the injury pyramid should also include mild injuries and even "near-misses". The Israeli National Trauma Registry has come a long way in the last few years. The eventual inclusion of all trauma centers in Israel will enable the establishment of a firm base for the allocation of resources by decision-makers.

Mitochondrial DNA depletion associated with partial complex II and IV deficiencies and 3-methylglutaconic aciduria.

We report a patient with mitochondrial DNA depletion, partial complex II and IV deficiencies, and 3-methylglutaconic aciduria. Complex II deficiency has not been previously observed in mitochondrial DNA depletion syndromes. The observation of 3-methylglutaconic and 3-methylglutaric acidurias may be a useful indicator of a defect in respiratory chain function caused by mitochondrial DNA depletion.

Outreach developmental services to children of patients in treatment for substance abuse.

OBJECTIVES: This report describes a model for delivering developmental services to children of patients in treatment for substance abuse. METHODS: A multidisciplinary team provides developmental evaluations of children at a substance abuse treatment clinic. RESULTS: In 3 years of operation, 85% of 117 children completed individualized developmental evaluations. Cognitive limitations were diagnosed in 69%, speech and language impairments in 68%, emotional or behavioral problems in 16%, and medical problems in 83%. Follow-up information on children completing evaluation indicated that 72% of eligible children are receiving services as recommended. CONCLUSIONS: This high-risk population of children of substance-abusing parents can be effectively served by providing developmental services at a substance abuse treatment program.

A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO).

Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait, although rarer autosomal dominant and recessive forms exist. We have studied males from four families with HED and immunodeficiency (HED-ID), in which the disorder segregates as an X-linked recessive trait. Affected males manifest dysgammaglobulinemia and, despite therapy, have significant morbidity and mortality from recurrent infections. Recently, mutations in IKK-gamma (NEMO) have been shown to cause familial incontinentia pigmenti (IP). Unlike HED-ID, IP affects females and, with few exceptions, causes male prenatal lethality. IKK-gamma is required for the activation of the transcription factor known as "nuclear factor kappa B" and plays an important role in T and B cell function. We hypothesize that "milder" mutations at this locus may cause HED-ID. In all four families, sequence analysis reveals exon 10 mutations affecting the carboxy-terminal end of the IKK-gamma protein, a domain believed to connect the IKK signalsome complex to upstream activators. The findings define a new X-linked recessive immunodeficiency syndrome, distinct from other types of HED and immunodeficiency syndromes. The data provide further evidence that the development of ectodermal appendages is mediated through a tumor necrosis factor/tumor necrosis factor receptor-like signaling pathway, with the IKK signalsome complex playing a significant role.