BACKGROUND & AIMS: OBJECTIVE:To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis.

METHODS:Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis.

RESULTS:At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay.

CONCLUSIONS:Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

背景与目标： 目标 : 研究巨细胞病毒 (CMV) 病毒载量与多形核白细胞 (PMNL) 和血浆样本中特定UL97突变之间的时间关系，该患者患有更昔洛韦耐药的CMV视网膜炎。
方法 : 使用非分子方法和定量聚合酶链反应 (PCR) 分析方法分析了连续的PMNL和血浆样品，以确定CMV病毒载量。使用巢式PCR和限制性内切酶分析对相同样品进行了更昔洛韦抗性最常见突变的筛选。
结果 : 在CMV视网膜炎进展时 (更昔洛韦6个月后)，在PMNL和血浆样品中发现CMV DNA载量迅速增加。这种增加与同一样品中出现特定突变 (V594) 和更昔洛韦耐药血液分离株的回收平行。但是，在该患者中，唯一可以基本预测CMV疾病进展的测试是使用PMNL的定量PCR测定，以及在较小程度上使用pp65抗原血症测定。
结论 : 使用敏感的检测方法 (例如PCR) 定量评估PMNL中的CMV病毒载量似乎是监测艾滋病患者抗病毒治疗的有希望的方法。此外，可以直接在PMNL和血浆样品中检测到赋予更昔洛韦抗性的常见突变。

BACKGROUND & AIMS: :Health care workers' perceptions of patient suffering have not been well studied. Patients and health care workers were invited to answer a single, open-ended question. To develop a survey tool that could be validated and used for future research, what health care workers thought causes or caused the most suffering for patients was compared with what patients actually identified as the cause of their worst suffering. Health care workers underestimated loss and significantly underestimated physical nonpainful symptoms as causes of maximal suffering. Communication, emotional, and systems issues were often overestimated by health care workers. Health care workers may not accurately perceive what causes the worst suffering for patients. More studies are needed.

背景与目标： : 医护人员对病人痛苦的看法没有得到很好的研究。邀请患者和医护人员回答一个开放式的问题。为了开发一种可以验证并用于未来研究的调查工具，将医护人员认为导致或导致患者最痛苦的原因与患者实际确定的最痛苦原因进行了比较。医护人员低估了损失，并大大低估了身体上的无痛苦症状，这是造成最大痛苦的原因。医护人员经常高估沟通，情感和系统问题。医护人员可能无法准确理解是什么导致了患者最严重的痛苦。需要更多的研究。

BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

背景与目标： 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量，疗效和副作用。符合条件的患者被转诊到姑息治疗计划，并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后，每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化，在之前的24小时内有四个或更少的抢救剂量，并且疼痛等级为无或轻度。如果连续96个小时保持这些标准，CIVI被认为等于CSCI。进入了57名患者，其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段，越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。剂量 (第2天) 为5.05 mg/hr，平均稳定s.c.剂量 (第4天) 为5.7 mg/hr (P = 0.01)。第2天的平均抢救剂量为每24小时0.83次，而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83，0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米，第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7，2.0 (P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点局部毒性 (轻度红斑) 的报告，需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量，都有足够的疼痛控制，并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明，静脉注射和南卡罗来纳州当作为连续输注给药时，大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。

BACKGROUND & AIMS: BACKGROUND:A large insurer in Hawaii mails annual reminders to its members regarding recommended health screenings. This study examined the associations between the characteristics of physicians visited after the reminders were sent and the health screenings received for breast, cervical, and colorectal cancers, and for diabetes and cholesterol. METHODS:The study population included members identified as needing health screenings from 2000 to 2003 based on age and gender criteria. The study used a longitudinal design focusing on the 12 months after reminders were sent. Data were analyzed using logistic regression examining physician visits, other health services, and receipt of health screenings by 1-month intervals subsequent to the reminder mailings. RESULTS:In adjusted, multivariable models, members who saw physicians they had not seen in the past year had odds ratios for obtaining health screenings 6 to 8 times higher than members who only saw previously visited physicians. This enhanced response occurred among members receiving their first, second, and third (or subsequent) annual reminder letter. The more physicians that were visited and who were new to the members, the more likely the members were to obtain health screenings. CONCLUSIONS:Members seeing physicians they had not seen in the past year had significantly higher screening rates than the members only seeing physicians they had previously visited. The results suggest that healthcare screening may receive less attention at repeat visits with a physician than at visits with a physician who is new to a member.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND:Side-stream spirometry offers a non-invasive method to monitor continuously respiratory mechanics in intubated patients. We studied the effects of different positions on dynamic lung compliance during anaesthesia. METHODS:The study consisted of 56 patients, operated in supine, prone, kneeling or lateral park-bench position. Dynamic lung compliance and inspiratory peak pressure were recorded after induction of anaesthesia, 15 min and 1 h after posturing the patient. RESULTS:The first measured compliances were comparable in all groups. The compliance in the lateral and the prone positions was significantly lower than in the supine position at 15 min (P < 0.01) and 1 h (P < 0.001) after the posture change. The peak inspiratory pressure was significantly lower in the kneeling position than in the other groups (P < 0.01 at the first measurement, P < 0.001 at the later measurements). No correlation was found between body mass index and compliance. CONCLUSION:We found that dynamic lung compliance decreased significantly upon change of posture from supine to lateral or prone position, whereas in the kneeling position no change in compliance was observed. We suggest that the kneeling position might be preferable to the prone position.

背景与目标：

BACKGROUND & AIMS: :Severe preeclampsia rarely occurs prior to 20 weeks of gestation except in pregnancies with triploidy. The patient reported herein is a 29-year-old primigravida who developed severe preeclampsia at 20 weeks of gestation. Evaluation of the pregnancy demonstrated a markedly abnormal quadruple screen. Amniocentesis demonstrated a fetus with triploidy, despite a normal appearance.

背景与目标： : 除三倍体妊娠外，妊娠20周前很少发生严重的先兆子痫。本文报道的患者是一名29岁的初产妇，在妊娠20周时出现严重的先兆子痫。对妊娠的评估显示出明显异常的四重筛查。羊膜穿刺术显示胎儿具有三倍体，尽管外观正常。

BACKGROUND & AIMS: The accuracy of cervicovaginal fetal fibronectin as a predictor of preterm birth was studied in patients with increased risk for preterm delivery (according to the Creasy-score). In a prospective blind observational study the smear from the posterior fornix vaginae of 56 pregnant patients without PROM was examined using a quantitative immunoassay for the detection of fetal fibronectin. The patients who tested positively for fetal fibronectin had significantly more preterm deliveries than those with a negative result (CHI square-test, p < 0.01, RR 5.1). Overall, sensitivity, specificity, positive and negative predictive values were 56%, 87%, 45% and 91%, respectively. In patients with preterm labor these values were 75%, 87%, 60%, and 93%, respectively. No patient with a negative result delivered preterm during the following two weeks. It is concluded that performing the fetal fibronectin test in patients with preterm labor is useful for the prediction of preterm birth. Routine testing in patients at increased risk (asymptomatic patients) is not recommended for lack of effectiveness.

背景与目标： 在早产风险增加的患者中研究了宫颈阴道胎儿纤维连接蛋白作为早产预测指标的准确性 (根据Creasy评分)。在一项前瞻性盲观察研究中，使用定量免疫测定法检查了56例无胎膜早破的孕妇的后穹窿阴道涂片，以检测胎儿纤连蛋白。胎儿纤连蛋白检测呈阳性的患者的早产明显多于阴性结果的患者 (卡方检验，p <0.01，RR 5.1)。总体而言，敏感性、特异性、阳性和阴性预测值分别为56% 、87% 、45% 和91%。在早产患者中，这些值分别为75%，87%，60% 和93%。在接下来的两周内，没有阴性结果的患者早产。结论对早产患者进行胎儿纤连蛋白试验对预测早产有一定的帮助。不建议对风险增加的患者 (无症状患者) 进行常规测试，因为缺乏有效性。

BACKGROUND & AIMS: Environmental pollution has become a major concern for the future of life on our planet; medical care, especially in hospitals, contributes significantly to this pollution. The increasing usage of highly-developed medical devices, drugs and disposable products are a drain on natural resources as well as financial ones. In this situation, it is a major task for hospital epidemiologists to maintain high standards of hygiene while reducing environmental pollution, reducing consumption of limited natural resources, and minimizing costs. The reduction of hospital waste, the control of polluting and toxic emissions, the avoidance of unnecessary disinfection procedures and disposables, the implementation of energy and water saving technologies are practicable measures in hospital ecology. To realize a sustainable development within hospitals, it is necessary that the need to maintain a balance between effective infection control and a good ecological environment is recognized and supported by health-care workers and the hospital management.

背景与目标： 环境污染已成为地球生命未来的主要问题; 医疗保健，尤其是医院的医疗保健，对这种污染有很大影响。高度发达的医疗设备，药品和一次性产品的使用日益增加，既消耗了自然资源，也消耗了金融资源。在这种情况下，医院流行病学家的主要任务是在减少环境污染的同时保持高标准的卫生，减少对有限自然资源的消耗并最大程度地降低成本。减少医院废物，控制污染和有毒排放物，避免不必要的消毒程序和一次性用品，实施节能节水技术是医院生态中的可行措施。为了实现医院内部的可持续发展，有必要在有效的感染控制和良好的生态环境之间保持平衡的需要得到医护人员和医院管理层的认可和支持。

BACKGROUND & AIMS: A patient with heterozygous protein S deficiency experienced cutaneous necrosis following subcutaneous heparin administration. Deficiencies of both protein C and protein S, known risk factors for the more frequently encountered coumarin necrosis, may predispose patients to this complication of heparin therapy as well. The putative association of protein S deficiency with cutaneous heparin necrosis could not be proven, however, since attempts to reproduce the heparin necrosis were unsuccessful.

背景与目标： 杂合蛋白S缺乏症患者在皮下注射肝素后出现皮肤坏死。蛋白C和蛋白S的缺乏是香豆素坏死较常见的已知危险因素，也可能使患者易患肝素治疗的这种并发症。然而，由于试图重现肝素坏死的尝试均未成功，因此无法证明蛋白质S缺乏症与皮肤肝素坏死的关系。

BACKGROUND & AIMS: CONTEXT:Chronic pain in patients with advanced cancer poses a serious clinical challenge. The Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (U.S. Adopted Name, nabiximols; Sativex(®)) is a novel cannabinoid formulation currently undergoing investigation as an adjuvant therapy for this treatment group. OBJECTIVES:This follow-up study investigated the long-term safety and tolerability of THC/CBD spray and THC spray in relieving pain in patients with advanced cancer. METHODS:In total, 43 patients with cancer-related pain experiencing inadequate analgesia despite chronic opioid dosing, who had participated in a previous three-arm (THC/CBD spray, THC spray, or placebo), two-week parent randomized controlled trial, entered this open-label, multicenter, follow-up study. Patients self-titrated THC/CBD spray (n=39) or THC spray (n=4) to symptom relief or maximum dose and were regularly reviewed for safety, tolerability, and evidence of clinical benefit. RESULTS:The efficacy end point of change from baseline in mean Brief Pain Inventory-Short Form scores for "pain severity" and "worst pain" domains showed a decrease (i.e., improvement) at each visit in the THC/CBD spray patients. Similarly, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scores showed a decrease (i.e., improvement) from baseline in the domains of insomnia, pain, and fatigue. No new safety concerns associated with the extended use of THC/CBD spray arose from this study. CONCLUSION:This study showed that the long-term use of THC/CBD spray was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase their dose of this or other pain-relieving medication over time, suggesting that the adjuvant use of cannabinoids in cancer-related pain could provide useful benefit.

背景与目标：

BACKGROUND & AIMS: :Inborn errors of vitamin B(12) (cobalamin) metabolism are characterized by decreased production of active cobalamin cofactors and subsequent deficiencies in the activities of methionine synthase and methylmalonyl-CoA mutase. With the recent discovery of the cblJ defect in two patients with phenotypes mimicking the cblF defect, there are nine genes known to be involved in cobalamin metabolism. The new defect is caused by mutations in the ABCD4 gene, encoding an ABC transporter. At the moment, there is no clear distinction between the cblJ and cblF defects either clinically or biochemically, and both defects result in blocks in the transport of cobalamin from the lysosome to the cytoplasm. A patient was diagnosed with hyperhomocysteinemia and methylmalonic aciduria at the age of 8 years. Incorporations of both [(14)C]propionate and [(14)C]methyltetrahydrofolate in cultured fibroblasts were within reference ranges and thus too high to allow for complementation analysis. We observed decreased synthesis of both adenosylcobalamin and methylcobalamin and accumulation of unmetabolized cyanocobalamin. Exome sequencing was performed to identify causative mutation(s) and Sanger re-sequencing was performed to validate segregation of mutation in the family. By this approach, a homozygous mutation, c.423C>G, in the ABCD4 gene was identified. Here, we report the successful application of exome sequencing for diagnosis of a rare inborn error of vitamin B(12) metabolism in a patient whose unusual presentation precluded diagnosis using standard biochemical and genetic approaches. The patient represents only the third known patient with the cblJ disorder.

背景与目标： : 维生素b (12) (钴胺素) 代谢的先天性错误的特征是活性钴胺素辅因子的产生减少，随后蛋氨酸合酶和甲基丙二酰辅酶a变位酶的活性不足。随着最近在两名表型模仿cblF缺陷的患者中发现cblJ缺陷，已知有9个基因与钴胺素代谢有关。新的缺陷是由编码ABC转运蛋白的ABCD4基因突变引起的。目前，无论是在临床上还是在生化上，cblJ和cblF缺陷之间都没有明确的区别，这两个缺陷都会导致钴胺素从溶酶体到细胞质的转运受到阻碍。一名患者在8岁时被诊断出患有高同型半胱氨酸血症和甲基丙二酸尿症。培养的成纤维细胞中 [(14)C] 丙酸酯和 [(14)C] 甲基四氢叶酸的加入都在参考范围内，因此太高，无法进行互补分析。我们观察到腺苷钴胺和甲钴胺的合成减少以及未代谢的氰钴胺的积累。进行外显子组测序以鉴定致病突变 (s)，并进行了Sanger重新测序以验证家族中突变的分离。通过这种方法，在ABCD4基因中发现了一个纯合突变，c.423C>G。在这里，我们报告了外显子组测序在诊断罕见的先天性维生素b (12) 代谢错误中的成功应用，该患者的异常表现无法使用标准的生化和遗传学方法进行诊断。该患者仅代表第三位已知的cblJ疾病患者。

BACKGROUND & AIMS: PURPOSE:To evaluate outcomes among early-stage breast cancer patients after conservative surgery and full-dose intraoperative radiotherapy electrons (ELIOT) by applying the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations for partial breast irradiation (APBI). MATERIALS AND METHODS:One-thousand eight-hundred and twenty-two patients were stratified into the three GEC-ESTRO categories of "good candidates", "possible candidates" and "contraindication" in order to assess outcomes. RESULTS:All the 1822 cases except 7 could be classified according to GEC-ESTRO groups: 573 patients met the criteria to be included in the "good candidates" group, 468 patients in the "possible candidates" group and 767 patients in the "contraindication" group. Median and mean follow-up length was 3.5 years (range 0-10.5 years) and 3.8 years (SD 2.2), respectively. The 5-year rate of in-breast tumor reappearances for "good candidates", "possible candidates" and "contraindication" groups were 1.9%, 7.4% and 7.7%, respectively (p 0.001). While the regional node relapse showed no difference, the rate of distant metastases was significantly different in the "contraindication" group compared to the other two categories, having a significant impact on survival. CONCLUSIONS:Among the ELIOT population, the GEC-ESTRO recommendations enabled the selection of the good candidates with a low rate of local recurrence, but failed to differentiate the "possible candidates" and the "contraindication" groups.

背景与目标：

BACKGROUND & AIMS: :Extensive laboratory testing is often performed in the emergency department evaluation of the new-onset seizure patient. To determine the utility of such testing, a prospective study of patients with a new-onset seizure presenting to the ED of an inner-city, university-affiliated teaching hospital was done. One hundred thirty-six patients were entered into the study between October 1984 and January 1988. All patients had uniform data collection performed. Pertinent historical information and physical examination findings were recorded on a standardized form before laboratory abnormality was a sole or contributory cause of the seizure disorder. These included four patients with hypoglycemia, four with hyperglycemia, two with hypocalcemia, and one with hypomagnesemia. Only two cases (hypoglycemia) were not suspected on the basis of findings on the history or physical examination. In ED patients, the incidence of a new-onset seizure due to a correctable metabolic disturbance is low. We conclude that, with the exception of the serum glucose, the extensive ED laboratory workup often done for the evaluation of a new-onset seizure is unnecessary. Further test ordering should be directed by the medical history and physical examination.

背景与目标： : 在急诊科对新发癫痫患者的评估中，经常进行广泛的实验室测试。为了确定这种测试的实用性，对向市中心大学附属教学医院的ED呈递的新发癫痫发作患者进行了前瞻性研究。在1984年10月和1988年1月之间，有136名患者进入了研究。所有患者均进行了统一的数据收集。在实验室异常是癫痫发作的唯一或促成原因之前，将相关的历史信息和体格检查结果记录在标准化表格上。其中包括4名低血糖患者，4名高血糖患者，2名低钙血症患者和1名低镁血症患者。根据病史或体格检查发现，仅怀疑有2例 (低血糖)。在ED患者中，由于可纠正的代谢紊乱而引起的新发癫痫发作的发生率较低。我们得出的结论是，除血清葡萄糖外，通常不需要进行广泛的ED实验室检查以评估新发癫痫发作。进一步的检查顺序应由病史和体格检查指示。

BACKGROUND & AIMS: OBJECTIVES:To evaluate first-year doctor of pharmacy (PharmD) students' communication apprehension, outcome expectations, and self-efficacy for communication over the duration of a 15-week patient-counseling course. DESIGN:First-year PharmD students (n=94) were asked to complete a 47-item, self-administered questionnaire on 3 occasions over the duration of the Nonprescription Drugs/Patient-Counseling course during the fall 2009 and 2010 semesters. ASSESSMENT:Eighty-seven of 94 students completed the survey instrument across data collection periods. There were significant reductions in total communication apprehension scores and in the communication apprehension subscores for meetings and public speaking, and significant increases in self-efficacy over time. No differences were found for outcome expectations of communication scores or the subscores for interpersonal conversations and group discussion. CONCLUSIONS:Communication apprehension may be decreased and self-efficacy for communication increased in first-year PharmD students through a 15-week Nonprescription Drugs/Patient-Counseling course using small-group practice sessions, case studies, and role-play exercises in conjunction with classroom lectures.

背景与目标：