Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule

BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease.     

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome. Eight patients (median age, 55.5 years; range, 32-65 years) with hematologic malignancies were included. Allogeneic peripheral blood stem cells were obtained from matched related (n=5) or matched unrelated (n=3) donors. Conditioning regimen was fludarabine 30 mg/m2 intravenously for 5 days, cyclophosphamide 1 g/m2/d intravenously for 2 days, and equine antithymocyte globulin 30 mg/kg/d for 2 days. GVHD prophylaxis included cyclosporine, methylprednisolone, and escalating doses of narrowband UV-B (311 nm) according to skin tolerance, 3 days a week, from 10 days before to 28 days after transplantation. The conditioning regimen and the UV-B therapy were well tolerated. Two patients received all 14 prescribed UV-B treatments (cumulative doses of 2000 and 3260 mJ/cm2, respectively) and 6 patients received 8 to 13 treatments with a cumulative dose range of 528-3465 mJ/cm2. There was a rapid decrease in epidermal CD1a+ cells by day of transplantation. Myeloid engraftment was rapid. One patient had secondary engraftment failure at 3 months and another had mixed chimerism at day 100. Seven of 8 patients developed severe acute GVHD (grade III, n=5; grade IV, n=2). Six had skin involvement, 5 had gastrointestinal involvement, and 1 had liver involvement. Four patients died (2 from sepsis, 1 from acute GVHD, and 1 from chronic GVHD). Four patients are alive (130-287 days), 3 with extensive chronic GVHD. We conclude that extended peritransplant UV-B therapy at the standard minimally erythemogenic dose is detrimental to the outcome of allogeneic stem cell transplantation. It is unclear how UV-B at this immunsuppressive dose might have altered skin and systemic cytokine and immune cell compositions in the host and increased GVHD- and treatment-related mortalities. Different UV-B dose and schedules should be further explored. However, although other phototherapeutic modalities may be effective against GVHD, extended UV-B therapy should not be used during early phases of decreased conditioning allogeneic transplantation.     

Early initiation of sex,drug-related risk behaviors,and sensation-seeking among urban,low-income African-American adolescents

The purpose of this study was to examine the relationship of early initiation of sex, drug-use, drug-trafficking, and sensation-seeking among urban, African-American adolescents. A longitudinal follow-up of 383 youth ages 9 to 15 years at baseline over four years with serial risk-assessments was used. Sexual experience and several drug-related risk behaviors increased significantly during the four-year study interval. Sensation-seeking scores were higher after the baseline assessment among youth reporting tobacco, alcohol, and marijuana use and were higher, both at baseline and through several follow-up assessments, among youth reporting drug-selling and sexual activity. At baseline, the correlations among drug-related risk behaviors were all strong, except those between initiation of sex and drug-related risk behaviors. However, over time, early initiators of sex were significantly more likely to report involvement in substance use and drug-delivery/sales than were late initiators. Youth reporting repeated involvement in drug-related activities were more likely to report intensive sexual involvement than they were to report experimental sex or no sex. Sensation-seeking scores were lower among youth reporting no involvement in risk behaviors. However, scores did not differ between youth exhibiting experimental behavior compared to youth demonstrating repeated risk involvement. These results support the need for alternative experiences for youth exhibiting high levels of sensation-seeking and the need for early drug/sexual risk prevention programs.     

Environmental conditions and variation in levels of sun exposure among children in child care

Sun exposure in childhood is 1 of the risk factors for developing skin cancer, yet little is known about levels of exposure at this age. This is particularly important in countries with high levels of ultraviolet radiation (UVR) such as Australia. Among 49 children 3 to 5 years of age attending child care centers, UVR exposure was studied under 4 conditions in a repeated measures design; sunny days, cloudy days, teacher’s instruction to stay in the shade, and a health professionals instruction to apply sunscreen. Three different data collection methods were employed: (a) completion of questionnaire or diary by parents and researcher, (b) polysulphone dosimeter readings, and (c) observational audits (video recording). Results of this study indicated that more than half the children had been sunburnt (pink or red) and more than a third had experienced painful sunburn (sore or tender) in the last summer. Most wore short sleeve shirts, short skirts or shorts and cap, that do not provide optimal levels of skin protection. However, sunscreen was applied to all exposed parts before the children went out to the playground. Over the period of 1 hr (9–10 a.m.) the average amount of time children spent in full sun was 22 min. On sunny days there was more variation across children in the amount of sun exposure received. While the potential amount of UVR exposure for young children during the hour they were outside on a sunny day was 1.45 MED (Minimum Erythemal Dose), they received on average 0.35 MED, which is an insufficient amount to result in an erythemal response on fair skin even without the use of sunscreen.     

BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.     

Ontogeny of eyeblink conditioning in the rat: Auditory frequency and discrimination learning effects

The present study sought to determine whether acoustic properties of the auditory conditioned stimulus (CS) or the use of a discrimination learning procedure would alter the emergence of eyeblink conditioning between postnatal Days 17 and 24 (Days 17–24) in the rat. In Experiment 1, we employed a 3 × 2 × 2 factorial design, involving pitch of the auditory CS (2.8, 5.0, and 9.0 kHz), training condition (paired vs. unpaired), and age (Days 17 or 24). Associative learning was evident at all tone frequencies on Day 24, but increased across frequencies on Day 17, although large age differences in conditioning remained at all tone frequencies. In Experiment 2, rat pups were trained to discriminate 2.8 versus 9.0-kHz tones on Day 17 or Day 24. Eyeblink conditioning increased with tone frequency on Day 24 but discriminative conditioning failed to appear on Day 17. These findings are discussed in relation to the role of auditory system maturation in the ontogeny of eyeblink conditioning. © 1995 Johnv Wiley & Sons, Inc.     

Dose-response analysis of cadmium in man: Body burden vs kidney dysfunction

The primary objective of this study was to develop dose-response relationships of cadmium in human beings. In vivo measurements of kidney, liver, urine, and blood cadmium, and urinary levels of β₂-microglobulin and total protein were obtained in 82 industrially exposed workers and 30 control subjects. The values of 200 μg/g creatinine for urinary β₂-microglobulin and 250 mg/g creatinine for urinary total protein were used to define the upper limit for normal kidney function. Forty-one of the cadmium workers (18 active, 23 retired) were classified as having abnormal kidney function; all control subjects had normal kidney function. Most workers with Cd above 70 ppm in the liver were judged to have some evidence of kidney abnormalities. The dose-response relationship for liver cadmium for the actively employed workers could be described by a linear logistic regression model:

$\text{ln}\text{p}\text{1?p}\text{0.118 ×}\text{liver cadmium (ppm)}\text{? 5.00}$

where p is the individual's probability of having kidney dysfunction. The loss of cadmium from the kidney following dysfunction prohibited a direct logistic analysis of the kidney cadmium data. However, when the linear relationship between kidney and liver cadmium for the subjects with normal kidney function was combined with the logistic equation for the liver, a predicted-response curve was obtained for the kidney. The logistic models predict a 50% probability of having kidney dysfunction at 38.4 mg for the kidney and 42.3 ppm for the liver, respectively.     

Patterns of E-Cigarette Use Among Primary Care Patients at an Urban Community Center

Tobacco use remains the leading cause of preventable disease and death in the US. The number of tobacco products has grown over the past decade. E-cigarette use has increased rapidly in recent years, but patterns and correlates of use have not been thoroughly assessed. We examined relationships among demographic factors, e-cigarette and conventional cigarette use in a large sample (N?=?12,409) of adult patients at a community health center in the Northeastern US. Overall, 13% (N?=?1675) of the sample reported ever using e-cigarettes. In logistic regression models, ever having used e-cigarettes was associated with younger age (ages 18–25; OR?=?3.5, p?<?0.001). Being transgender (OR?=?1.8, p?<?0.001), bisexual (OR?=?1.5, p?<?0.001), un-partnered (OR?=?1.5, p?<?0.001), having a lower income (OR?=?1.6, p?<?0.001) or a high BMI (OR?=?1.4, p?=?0.009) were associated with increased odds of use, whereas being a woman (OR?=?0.7, p?<?0.001) or Black/African American (OR?=?0.7, p?=?0.007) were associated with lower odds of use. Of the participants who reported e-cigarette use, a majority also endorsed current or former use of conventional cigarettes. Individuals who formerly used conventional cigarettes were nearly three times more likely to report daily e-cigarette use than current users. Among primary care patients at a community health center, e-cigarette use was reported by a sizeable portion of the sample. Overall, odds of use were higher in certain patient populations, and individuals who formally used cigarettes were more likely to report e-cigarette use than individuals who currently smoke, suggesting that e-cigarettes may be functioning as a cessation aid or a strategy to reduce conventional cigarette use.

     

Beyond your paycheck: an employee benefits primer

Most jobs are worth much more than their salaries. Paid vacations, sick leave, pensions, health insurance, and other benefits can add almost $3 to every $10 you earn in salary.     

Comparison of Ifosfamide versus cyclophosphamide in combination with Cisplatin and Doxorubicin (adriamycin), as first-line therapy for advanced epithelial ovarian-cancer - report of a pilot-study

Cisplatin induction therapy followed by combination chemotherapy employing cisplatin, doxorubicin, and ifosfamide was administered to 25 consecutive patients with FIGO stage III:or IV epithelial ovarian cancer as first-line therapy following cytoreductive surgery. A median of seven (3-10) courses of combination chemotherapy were administered. Myelotoxicity necessitated dose attenuation in 20 (80%) patients. Microscopic hematuria was observed in one (4%) patient. Serious central neurotoxicity occurred in two (8%) patients. A surgically documentable response to therapy was observed in 16 of 19 (84%) patients who underwent second-look laparotomy. Thirteen (68%) patients had a surgical complete response, three (12%) patients had a surgical partial response, and three (12%) patients demonstrated progression of disease. The estimated two-year survival for the study population was 81%. The results observed in the current study were compared to those reported for a population of 40 patients with advanced ovarian cancer treated with cisplatin, doxorubicin, and cyclophosphamide (PAC). Patients treated with PAI had significantly (p=0.04) fewer episodes of sepsis, a significantly (p=0.02) greater percentage of patients requiring dose reduction secondary to myelotoxicity, and a significantly (p=0.02) higher surgical complete response rate. The two-year survival for patients treated with PAI of 81% and that for patients treated with PAC of 68%, do not differ significantly (p=0.39). The two-year disease-free survival for patients treated with PAI of 34% and the two-year disease-free survival of 55% for patients treated with PAC do not differ significantly (p=0.99). The combination of cisplatin, doxorubicin, and ifosfamide is effective as first-line therapy in the treatment of advanced epithelial ovarian cancer, but a significant advantage over the less costly standard regimen which employs cisplatin, doxorubicin and cyclophosphamide is not demonstrable in the current study.