Palliative medicine consultation for preparedness planning in patients receiving left ventricular assist devices as destination therapy

OBJECTIVE: To assess the benefit of proactive palliative medicine consultation for delineation of goals of care and quality-of-life preferences before implantation of left ventricular assist devices as destination therapy (DT).PATIENTS AND METHODS: We retrospectively reviewed the cases of patients who received DT between January 15, 2009, and January 1, 2010.RESULTS: Of 19 patients identified, 13 (68%) received proactive palliative medicine consultation. Median time of palliative medicine consultation was 1 day before DT implantation (range, 5 days before to 16 days after). Thirteen patients (68%) completed advance directives. The DT implantation team and families reported that preimplantation discussions and goals of care planning made postoperative care more clear and that adverse events were handled more effectively. Currently, palliative medicine involvement in patients receiving DT is viewed as routine by cardiac care specialists.CONCLUSION: Proactive palliative medicine consultation for patients being considered for or being treated with DT improves advance care planning and thus contributes to better overall care of these patients. Our experience highlights focused advance care planning, thorough exploration of goals of care, and expert symptom management and end-of-life care when appropriate.DT = destination therapy; ICD = implantable cardioverter-defibrillator; LVAD = left ventricular assist device; PM = palliative medicine; QOL = quality of life

You matter because you are you. You matter to the last moment of your life, and we will do all we can, not only to help you die peacefully, but also to live until you die.Dame Cicely Saunders

The left ventricular assist device (LVAD) is a promising technology that supports circulation in patients with advanced heart failure. Originally developed to bridge patients to heart transplant, the LVAD is being used as destination therapy (DT) for patients who are not candidates for heart transplant. Compared with medical therapy, use of DT improves survival, quality of life (QOL), and functional status in appropriately selected patients with advanced heart failure.^1-5 In our experience at Mayo Clinic, the 2-year survival rate of patients receiving DT is 75%.⁶ However, as a result of occasional adverse events (eg, stroke, infection, or multiorgan failure), some patients or their surrogate decision-makers may request withdrawal of LVAD support.^4,7,8 In other situations, patients or caregivers may become overwhelmed with financial and psychosocial issues related to DT^8-11 and are at risk of burnout and isolation because of outpatient needs and limited community support.^11-14Several analyses^7,15,16 have concluded that goals of care of patients receiving DT are often undefined. Many patients either have inadequate advance directives that do not address potential problems (such as worsening comorbid conditions, complications, and worsening QOL) or simply lack advance care documents.^7,16,17 Without clearly defined goals and/or explicit advance directives, DT may merely maintain circulation in a moribund patient, a situation referred to as “destination nowhere.”¹⁸ Also, protocols and processes regarding LVAD management and comfort at the end of life are often lacking^7,17; hence, ethical quandaries (eg, withdrawal of device support) may arise.^19,20To avoid situations in which advance care wishes are unclear or unknown, palliative medicine (PM) consultation has been suggested^8,17,21-23 to address end-of-life preferences, facilitate advance care planning, manage symptoms, and maximize QOL. Several authors have called for PM involvement in patients with advanced heart disease to improve health status and QOL,^24-29 and a recent randomized study of early palliative care vs standard care in advanced lung cancer has demonstrated improved QOL, improved mood, and survival benefit.³⁰ Herein, we describe our initial experience with proactive PM consultation in patients receiving DT.     

Hypoglycemia and Outcome in Critically Ill Patients

OBJECTIVE: To determine whether mild or moderate hypoglycemia that occurs in critically ill patients is independently associated with an increased risk of death.PATIENTS AND METHODS: Of patients admitted to 2 hospital intensive care units (ICUs) in Melbourne and Sydney, Australia, from January 1, 2000, to October 14, 2004, we analyzed all those who had at least 1 episode of hypoglycemia (glucose concentration, <81 mg/dL). The independent association between hypoglycemia and outcome was statistically assessed.RESULTS: Of 4946 patients admitted to the ICUs, a cohort of 1109 had at least 1 episode of hypoglycemia (blood glucose level, <81 mg/dL). Of these 1109 patients (22.4% of all admissions to the intensive care unit), hospital mortality was 36.6% compared with 19.7% in the 3837 nonhypoglycemic control patients (P<.001). Even patients with a minimum blood glucose concentration between 72 and 81 mg/dL had a greater unadjusted mortality rate than did control patients (25.9% vs 19.7%; unadjusted odds ratio, 1.42; 95% confidence interval, 1.12-1.80; P=.004.) Mortality increased significantly with increasing severity of hypoglycemia (P<.001). After adjustment for insulin therapy, hypoglycemia was independently associated with increased risk of death, cardiovascular death, and death due to infectious disease.CONCLUSION: In critically ill patients, an association exists between even mild or moderate hypoglycemia and mortality. Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more severe the hypoglycemia, the greater the risk of death.APACHE = Acute Physiology and Chronic Health Evaluation; AUC = area under the curve; CI = confidence interval; ICU = intensive care unit; IIT = intensive insulin therapy; NICE-SUGAR = Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation; OR = odds ratioUntil recently, intensive insulin therapy (IIT) had been recommended to improve patient outcome^1-3 despite its association with an increased risk of hypoglycemia.^4-11 However, hypoglycemia, like hyperglycemia,^12-16 has emerged as a possible predictor of mortality and morbidity in critically ill patients.^5,17-21The NICE-SUGAR (Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation) trial found that IIT increased 90-day mortality compared with conventional treatment in critically ill patients.^22,23 In that trial, the incidence of severe hypoglycemia (blood glucose level, ≤40 mg/dL (to convert to mmol/L, multiply by 0.0555) was significantly higher with IIT. Furthermore, the relative risk of severe hypoglycemia was 13.7, more than twice that seen in prior randomized controlled trials.^5,9-11 Thus, the incidence of hypoglycemia might be a key element of blood glucose control in critically ill patients, although no causal link between hypoglycemia and mortality has been demonstrated. However, no consensus exists on the definition of hypoglycemia in patients with critical illness.²⁴ Studies thus far have mainly focused on severe hypoglycemia.For editorial comment, see page 215We sought to determine the epidemiology and independent association of hypoglycemia in the intensive care unit (ICU). We hypothesized that mild or moderate hypoglycemia would be common and would be independently associated with an increased risk of death.     

Sedation Depth During Spinal Anesthesia and the Development of Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Repair

OBJECTIVE: To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium.PATIENTS AND METHODS: We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (≥65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, ≥80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery.RESULTS: From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean ± SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5±1.5 days vs 1.4±4.0 days; P=.01).CONCLUSION: The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted.Trial Registration: clinicaltrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00590707","term_id":"NCT00590707"}}NCT00590707BIS = bispectral index; CAM = Confusion Assessment Method; CI = confidence interval; ICU = intensive care unit; MMSE = Mini-Mental State Examination; NNT = number needed to treat; OR = odds ratio; PACU = postanesthesia care unitPostoperative delirium occurs in elderly patients at an overall prevalence of 10% to 37%.^1,2 The prevalence ranges from 0% to 73%, depending on the study and type of surgery,² with a prevalence of 16% to 62% after hip fracture repair.^3-5 Although postoperative delirium usually resolves within 48 hours of onset,⁶ delirium can persist and is associated with poor functional recovery, increased length of stay, higher costs, and greater likelihood of placement in an assisted living facility after surgery.^3,5,7-13 Therefore, interventions capable of reducing the occurrence of postoperative delirium would be important from a public health perspective, but relatively few proposed interventions have proven efficacious.^14-16Several demographic and perioperative variables are associated with postoperative delirium in elderly patients after hip fracture repair, the most important of which is preoperative dementia.^3,7,17-20 Other risk factors for postoperative delirium include age, systemic disease, functionality, and psychoactive medications.^3,19 Inhalational and intravenous anesthetics, opioids, benzodiazepines, and anticholinergic drugs are all known or suspected risk factors for postoperative delirium.^21-26 Although perioperative opioids are a risk factor for postoperative delirium, they are difficult to avoid after major surgery,^17,25 especially because undertreated pain may increase the risk of postoperative delirium.¹⁷ Transfusion and perioperative medical complications may also be important.³ Unfortunately, most of these risk factors are not readily modified at the time of surgery.For editorial comment, see page 12Anesthetic technique is a potentially modifiable risk factor for postoperative delirium. Although administration of many drugs can be avoided or limited with regional anesthetic techniques and reductions in the prevalence of postoperative delirium have been observed with regional anesthesia, these results are inconsistent.^27,28 This inconsistency may be explained by reports that sedation levels consistent with general anesthesia are frequently observed during regional anesthesia^29-32 and, at least in an intensive care setting, that sedation level is an important risk factor for delirium.²³ The intravenous anesthetic propofol is commonly used to provide intraoperative sedation during spinal anesthesia and other regional anesthetics. Although propofol may have longer-term effects on some neurons of the central nervous system in vitro,³³ it is generally considered safe and without persistent aftereffects.We hypothesized that minimizing sedation depth during spinal anesthesia for hip fracture repair in elderly patients could decrease the occurrence of postoperative delirium. Therefore, we performed a randomized controlled trial that compared the prevalence of postoperative delirium after hip fracture repair with spinal anesthesia with either deep or light propofol sedation.     

Association of TNFSF8 polymorphisms with peripheral neutrophil count

OBJECTIVE: To investigate the association between 347 single-nucleotide polymorphisms within candidate genes of the tumor necrosis factor, interleukin 1 and interleukin 6 families with neutrophil count.PATIENTS AND METHODS: Four hundred cases with heart failure after myocardial infarction (MI) were matched by age, sex, and date of incident MI to 694 controls (MI without post-MI heart failure). Both genotypes and neutrophil count at admission for incident MI were available in 314 cases and 515 controls.RESULTS: We found significant associations between the TNFSF8 poly morphisms rs927374 (P=5.1 x 10^–5) and rs2295800 (P=1.3 x 10^–4) and neutrophil count; these single-nucleotide polymorphisms are in high linkage disequilibrium (r²=0.97). Associations persisted after controlling for clinical characteristics and were unchanged after adjusting for case-control status. For rs927374, the neutrophil count of GG homozygotes (7.6±5.1) was 16% lower than that of CC homozygotes (9.0±5.2).CONCLUSION: The TNFSF8 polymorphisms rs927374 and rs2295800 were associated with neutrophil count. This finding suggests that post-MI inflammatory response is genetically modulated.GWAS = genome-wide association study; HF = heart failure; IL = interleukin; MAF = minor allele frequency; MI = myocardial infarction; SNP = single-nucleotide polymorphism; TNF = tumor necrosis factorMyocardial infarction (MI) triggers an inflammatory response.^1,2 Early in the post-MI inflammatory phase, proinflammatory cytokines with chemoattractant properties are activated and contribute to neutrophil recruitment to the infarcted area.^1,2 In addition, proinflammatory cytokines³ promote demargination of intravascular neutrophils, acceleration of the release of neutrophils by the bone marrow, and activation of neutrophils.^4-6 Indeed, the early post-MI period is frequently marked by activation of neutrophils^7,8 and elevation of the peripheral neutrophil count. We have previously demonstrated that neutrophil count on incident MI presentation is strongly and independently associated with adverse outcomes.⁹ Secondary analysis of clinical trials of ST-elevation MI also showed associations between peripheral neutrophil count and post-MI adverse outcomes.¹⁰The proinflammatory cytokines include the tumor necrosis factor (TNF), interleukin (IL) 1 and IL-6 families,^2,11,12 which are not constitutively expressed in the heart.^13,14 However, these cytokines are consistently and rapidly expressed in response to myocardial injury, including MI.^15-19 The short-term limited expression of cytokines provides the heart with an adaptive response to injury. This protective response may occur at the cost of unwanted deleterious effects, including left ventricular dysfunction,^20-23 which may manifest clinically as heart failure (HF) syndrome. In HF, increased levels of both TNF and IL-6 are associated with worse survival.^6,24 After MI, levels of IL-6 are associated with an increase in left ventricular end-diastolic volume and remodeling.²⁵Production of proinflammatory cytokines is genetically modulated with heritability estimates ranging from 53% to 86%.^26,27 It is unknown whether genetic variants of the proinflammatory cytokine families are associated with post-MI inflammation as assessed by the inflammatory marker of neutrophil count. Therefore, we investigated the association between 347 single-nucleotide polymorphisms (SNPs) within candidate genes of the proinflammatory cytokine families, including TNF (18 genes), IL-1 (10 genes), and IL-6 (12 genes), and peripheral neutrophil count in a nested case-control study from the Olmsted County, Minnesota, cohort of incident MI.²⁸ This study tests the hypothesis that variants within candidate genes of these proinflammatory cytokine families are associated with peripheral neutrophil count in patients with MI.     

Pilot Study of Providing Online Care in a Primary Care Setting

OBJECTIVE: To study the use of e-visits in a primary care setting.PATIENTS AND METHODS: A pilot study of using the Internet for online care (“e-visits”) was conducted in the Department of Family Medicine at Mayo Clinic in Rochester, MN. Patients in the department preregistered for the service, and then were able to use the online portal for consultations with their primary care physician. Use of the online portal was monitored and data were collected from November 1, 2007, through October 31, 2009.RESULTS: During the 2-year period, 4282 patients were registered for the service. Patients made 2531 online visits, and billings were made for 1159 patients. E-visits were submitted primarily by women during working hours and involved 294 different conditions. Of the 2531 e-visits, 62 (2%) included uploaded photographs, and 411 (16%) replaced nonbillable telephone protocols with billable encounters. The e-visits made office visits unnecessary in 1012 cases (40%); in 324 cases (13%), the patient was asked to schedule an appointment for a face-to-face encounter.CONCLUSION: Although limited in scope, to our knowledge this is the largest study of online visits in primary care using a structured history, allowing the patient to enter any problem, and billing the patient when appropriate. The extent of conditions possible for treatment by online care was far-ranging and was managed with a minimum of message exchanges by using structured histories. Processes previously given as a free service or by nurse triage and subject to malpractice (protocols) were now documented and billed.Some fundamental aspects of transforming primary care include eliminating barriers to access, using technology to communicate with patients, and enhancing financial performance.¹ Currently, it is possible for patients to use the Internet to see laboratory test results, make appointments, pay bills, and review their charts.² Some reports have shown improved patient satisfaction with use of these options.^3-5 Several articles have discussed electronic messaging (e-mails) as a way to improve efficiency by decreasing patient telephone calls to the physician''s office.^6-9 Various reports have described the use of the Internet to manage conditions such as depression,^10,11 diabetes mellitus,¹² hypertension,^13,14 and sexually transmitted diseases¹⁵ and also to assist with breastfeeding support,¹⁶ previsit well child encounters,¹⁷ and communication with patients in safety net practices.¹⁸ Guidelines have been established for providing medical care on the Internet (“e-visits”).¹⁹ Patients in primary care practices also have indicated a willingness to pay for online services.²⁰However, implementation of billable e-visits has been slow. “Reasons for provider hesitation to adopt e-visit technologies include fears of being overburdened by electronic communication, improper use of electronic communication by patients, lack of reimbursement schemes, legal and regulatory issues, and concerns over security, privacy, and confidentiality.”²¹ Also, electronic consultations to date have generally used online forms or secure e-mail. The information in these formats is unstructured and often lacks sufficient information, prompting the clinician to respond to the patient to request further information, which results in delays.²² Furthermore, the lack of organization in an e-mail makes it difficult to code complexity; consequently, the same fee is often charged for all online consultations, regardless of complexity.²³For editorial comment, see page 701Isolated reports of the use of online consultations have been disappointing. For example, despite indications that electronic communication could decrease health care costs²⁴ and provide reimbursement from patients,^25,26 Fairview Health System has reported only 10 e-visits per week in a system with 400 physicians,²⁷ and Blue Cross of Minnesota processed about 30 e-visits per month in July 2008 and 90 e-visits per month in July 2009 (D. Hiza, MD, written communication, February 2010).Studies have not described a portal for online patient consultations that has a structured medical history. Structured computerized histories were first described in the 1960s by Mayne et al²⁸ and Slack et al.²⁹ Their work included using the telephone and teletype with patients from distant locations providing their histories.³⁰ The evidence for using computerized histories to produce more organized histories, detect new symptoms, and provide greater patient satisfaction with improved clinician performance has been reviewed.³¹We conducted a pilot study of online patient visits in a primary care setting using structured histories and the possibility of the patients being billed for the service.     

Clinical Outcomes of Video-Assisted Thoracoscopic Lobectomy

OBJECTIVE: To review our experience with video-assisted thoracoscopic (VATS) lobectomy with respect to morbidity, mortality, and short-term outcome.PATIENTS AND METHODS: VATS lobectomies were performed in 56 patients between July 6, 2006, and February 26, 2008. Two patients declined consent for research participation and were excluded. Clinical data for 54 patients were collected from medical records and analyzed retrospectively.RESULTS: The studied cohort included 19 men (35%) and 35 women (65%) with a median age of 67.5 years (minimum-maximum, 21-87 years; interquartile range [IQR], 59-74 years). Median duration of operation for VATS lobectomy was 139 minutes (minimum-maximum, 78-275 minutes; IQR, 121-182 minutes). Two cases (4%) required conversion to open lobectomy. Median time to chest tube removal was 2 days (minimum-maximum, 1-12 days; IQR, 1.3-3.8 days). Median length of stay was 4 days (minimum-maximum, 1-12 days; IQR, 4-7 days). There was no operative mortality.CONCLUSION: VATS lobectomy is safe and feasible for pulmonary resection. This minimally invasive approach may allow patients to benefit from lobectomy with shorter recovery times and hospital stays compared with conventional open thoracotomy.IQR = interquartile range; NSCLC = non-small cell lung cancer; VATS= video-assisted thoracoscopicVideo-assisted thoracoscopic (VATS) surgery was first described by several groups in the early 1990s. Initial applications included exploration of the chest, management of pleural effusion or pneumothorax, and limited resection of lung nodules.^1-6 In subsequent years it has achieved broad application in clinical practice as a minimally invasive tool for multiple indications.^7-20 Techniques for VATS lobectomy as an oncologic resection emerged after this experience, with many large retrospective series showing the feasibility and safety of this minimally invasive surgical approach.^{11,12,14-16,21-23} Although the existing retrospective data suggest equivalent oncologic outcomes with VATS lobectomy and lobectomy using a conventional open thoracotomy, prospective studies are needed to confirm this hypothesis and are ongoing.²⁴ Compared with the open approach, VATS lobectomies have the potential advantage of decreased postoperative pain and a shorter hospital length of stay.^25-27 Other proposed advantages of a thoracoscopic approach include decreased blood loss, fewer postoperative complications, preserved pulmonary function, decreased inflammatory response, and a more rapid return to preoperative activity.^{10,11,14,15,20,25} If adjuvant chemotherapy or radiation therapy is indicated, a potential shorter postoperative recovery time may allow adjuvant treatment at a shorter postoperative interval with better adherence and treatment completion rates.^12,28VATS lobectomies have been used routinely in our department since July 2006. This report reviews our experience with the VATS approach with respect to morbidity and mortality as well as its potential effect on the length of patient hospitalization.     

Blood storage duration and biochemical recurrence of cancer after radical prostatectomy

OBJECTIVE: To test the hypothesis that perioperative transfusion of allogeneic and autologous red blood cells (RBCs) stored for a prolonged period speeds biochemical recurrence of prostate cancer after prostatectomy.PATIENTS AND METHODS: We evaluated biochemical prostate cancer recurrence in men who had undergone radical prostatectomy and perioperative blood transfusions from July 6, 1998, through December 27, 2007. Those who received allogeneic blood transfusions were assigned to nonoverlapping “younger,” “middle,” and “older” RBC storage duration groups. Those who received autologous RBC transfusions were analyzed using the maximum storage duration as the primary exposure. We evaluated the association between RBC storage duration and biochemical recurrence using multivariable Cox proportional hazards regression.RESULTS: A total of 405 patients received allogeneic transfusions. At 5 years, the biochemical recurrence–free survival rate was 74%, 71%, and 76% for patients who received younger, middle, and older RBCs, respectively; our Cox model indicated no significant differences in biochemical recurrence rates between the groups (P=.82; Wald test). Among patients who received autologous transfusions (n=350), maximum RBC age was not significantly associated with biochemical cancer recurrence (P=.95). At 5 years, the biochemical recurrence–free survival rate was 85% and 81% for patients who received younger and older than 21-day-old RBCs, respectively.CONCLUSION: In patients undergoing radical prostatectomy who require RBC transfusion, recurrence risk does not appear to be independently associated with blood storage duration.PSA = prostate-specific antigen; RBC = red blood cellProstate cancer is the most common malignant neoplasm in men, and radical prostatectomy is among the primary therapies for localized prostate cancer. The biochemical recurrence rate 5 years after prostatectomy ranges from 70% to 90%.^1,2 Improvements in the surgical technique have decreased the amount of intraoperative blood loss occurring during radical prostatectomy³; however, substantial numbers of patients still require perioperative blood transfusions.^4-6Blood transfusions are associated with adverse reactions, including postoperative infections and transfusion-related immune perturbations.^7,8 Allogeneic leukocytes present in the transfused blood are thought to suppress host cellular immune responses.^9,10 Furthermore, the immunodepressant effect is secondary to an imbalance of accumulated cytokines and proinflammatory mediators in the transfused blood against decreased production of lymphocyte stimulating cell-mediated cytokines, such as interleukin 2,^9,10 and increased release of immunosuppressive prostaglandins in the patient undergoing transfusion.^11,12In cancer patients, perioperative blood transfusion has long been suspected of reducing long-term survival,^4,13 but available evidence is inconsistent. It is also unclear which components of transfused blood underlie the cancer-promoting effects reported by some studies.^14,15 An important factor associated with the deleterious effects of blood transfusion is the storage age of the transfused blood units.¹⁶ A recent study using 2 animal models demonstrated that prolonged storage (>9 days) of transfused red blood cells (RBCs) was a critical deleterious factor.¹⁷ Therefore, it seems likely that cancer recurrence may also be worsened after the transfusion of older blood. No clear cutoff point has been established to define old vs young blood; however, a recent large clinical study defined old blood as RBCs with a storage time longer than 14 days.¹⁸We thus evaluated the association between RBC storage duration and biochemical prostate cancer recurrence after radical prostatectomy. Specifically, we tested the hypothesis that perioperative transfusion of allogeneic and autologous RBCs stored for a prolonged period is associated with earlier biochemical recurrence of prostate cancer after prostatectomy.     

Health Care Utilization and Cost Burden of Herpes Zoster in a Community Population

OBJECTIVE: To conduct a population-based study to assess health care utilization (HCU) and costs associated with herpes zoster (HZ) and its complications, including postherpetic neuralgia (PHN) and nonpain complications, in adults aged 22 years and older.PATIENTS AND METHODS: Medical record data on HCU were abstracted for all confirmed new cases of HZ from January 1, 1996, through December 31, 2001, among residents of Olmsted County, Minnesota. Herpes zoster-related costs were estimated by applying the Medicare Payment Fee Schedule to health care encounters and mean wholesale prices to medications. All costs were adjusted to 2006 US dollars using the medical care component of the Consumer Price Index.RESULTS: The HCU and cost of the 1669 incident HZ cases varied, depending on the complications involved. From 3 weeks before to 1 year after initial diagnosis, there were a mean of 1.8 outpatient visits and 3.1 prescribed medications at a cost of $720 for cases without PHN or nonpain complications compared with 7.5 outpatient visits and 14.7 prescribed medications at a cost of $3998 when complications, PHN, or nonpain complications were present.CONCLUSION: The annual medical care cost of treating incident HZ cases in the United States, extrapolated from the results of this study in Olmsted County, is estimated at $1.1 billion. Most of the costs are for the care of immunocompetent adults with HZ, especially among those 50 years and older.ED = emergency department; HCU = health care utilization; HZ = herpes zoster; ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification; PHN = postherpetic neuralgia; REP = Rochester Epidemiology ProjectNearly 1 million new cases of herpes zoster (HZ) occur annually in the United States.^1,2 Herpes zoster results from reactivation of the varicella-zoster virus, which remains dormant after infection with chickenpox. Declining cellular immunity associated with aging and immunocompromising conditions increase the risk of HZ and HZ complications.^3-5 However, most HZ cases (>90%) occur in immunocompetent people.^1,2 Herpes zoster can adversely affect a person''s health-related quality of life^6-8 because of complications such as eye and other nonpain complications ² as well as acute and chronic pain (postherpetic neuralgia [PHN]) that can result in severe activity limitations and sleep disturbances.^2,6,9Claims data have been used to estimate the health care utilization (HCU) and cost of HZ in the United States.^10,11 However, such data have potential limitations. Claims data may not capture all the HCU and costs attributable to the complications of HZ, including PHN and nonpain complications. In the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM),¹² few HZ complication-specific diagnostic codes are available, and they may not be used reliably. Although there is an ICD-9-CM diagnostic code for PHN, there is no standard definition for PHN that is used by all physicians. In addition, not all HZ-related visits are coded with a zoster-specific diagnostic code, especially visits that occur before definitive diagnosis. Medications, laboratory tests, and procedures are not directly linked to disease codes, making attribution to HZ difficult.¹³ Coding errors and the use of codes to refer to differential diagnoses may also result in incorrectly assigning claims to HZ.²We present data on medical care for HZ from a retrospective, population-based study of all Olmsted County, Minnesota, residents aged 22 years and older who were diagnosed by a physician as having a new episode of HZ from January 1, 1996, through December 31, 2001. The HCU data were collected through an extensive review of medical records to overcome some of the problems encountered when using claims data to attribute HCU to HZ. This work provides a comprehensive assessment of the HCU and economic burden of HZ in a community setting.     

Hospitalized Patients' Understanding of Their Plan of Care

OBJECTIVE: To evaluate hospitalized patients'' understanding of their plan of care.PATIENTS AND METHODS: Interviews of a cross-sectional sample of hospitalized patients and their physicians were conducted from June 6 through June 26, 2008. Patients were asked whether they knew the name of the physician and nurse responsible for their care and specific questions about 6 aspects of the plan of care for the day (primary diagnosis, planned tests, planned procedures, medication changes, physician services consulted, and the expected length of stay). Physicians were interviewed and asked about the plan of care in the same fashion as for the patients. Two board-certified internists reviewed responses and rated patient-physician agreement on each aspect of the plan of care as none, partial, or complete agreement.RESULTS: Of 250 eligible patients, 241 (96%) agreed to be interviewed. A total of 233 (97%) of 241 physicians completed the interview, although sample sizes vary because of missing data elements. Of 239 patients, 77 (32%) correctly named at least 1 of their hospital physicians, and 143 patients (60%) correctly named their nurses. For each aspect of care, patients and physicians lacked agreement on the plan of care in a large number of instances. Specifically, there was no agreement between patients and physicians on planned tests or procedures for the day in 87 (38%) of 229 instances and in 22 (10%) of 220 instances. Complete agreement on the anticipated length of stay occurred in only 85 (39%) of 218 instances.CONCLUSION: A substantial portion of hospitalized patients do not understand their plan of care. Patients'' limited understanding of their plan of care may adversely affect their ability to provide informed consent for hospital treatments and to assume their own care after discharge.High-quality communication between health care professionals and their patients is fundamental in ensuring comprehension and in providing effective care. Studies in ambulatory settings document that agreement between patients and physicians regarding the diagnosis and treatment plan is associated with improved medication adherence and better outcomes.^1-4 Hospital settings pre sent unique challenges to the patient-physician relationship, including the lack of a prior relationship, rapid pace of clinical care, and dynamic nature of inpatient medical teams. Prior studies revealed important findings about the relationship between hospitalized patients and health care professionals. Most hospitalized patients are unable to correctly identify their physicians or nurses,^5-8 and patients in teaching hospitals have difficulty understanding their physicians'' level of training.^7,9,10 At hospital discharge, patients are frequently unable to list their diagnoses and the names, purpose, and adverse effects of medications.^11,12 Moreover, physicians frequently overestimate patients'' understanding of the treatment plan at hospital discharge¹¹ and may not recognize patients with low health literacy.¹³Although deficits in patients'' understanding of the plan of care in the ambulatory setting and at hospital discharge are well documented, no studies have evaluated patients'' understanding of their plan of care during hospitalization. Yet, case studies clearly demonstrate the hazards patients may encounter when they do not fully comprehend their diagnostic and treatment plan in the hospital.^14,15 We hypothesized that disagreement between patients and their physicians on the plan of care might be present early in the hospital stay. We sought to characterize patients'' understanding of their plan of care during hospitalization and factors associated with improved understanding.     

Fluorescence In Situ Hybridization to Visualize Genetic Abnormalities in Interphase Cells of Acinar Cell Carcinoma, Ductal Adenocarcinoma, and Islet Cell Carcinoma of the Pancreas

OBJECTIVE: To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.PATIENTS AND METHODS: Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS. These FISH probes were used with control probes to distinguish among various kinds of chromosome abnormalities of number and structure.RESULTS: FISH abnormalities were observed in 12 (80%) of 15 patients with pancreatic cancer: 5 of 5 patients with acinar cell carcinoma, 5 of 5 patients with ductal adenocarcinoma, and 2 (40%) of 5 patients with islet cell carcinoma. All 3 specimens of pancreatic tissue without neoplasia had normal FISH results. Gains of CTNNB1 due to trisomy 3 occurred in each tumor with acinar cell carcinoma but in none of the other tumors in this study. FISH abnormalities of all other cancer genes studied were observed in all forms of pancreatic tumors in this investigation.CONCLUSION: FISH abnormalities of CTNNB1 due to trisomy 3 were observed only in acinar cell carcinoma. FISH abnormalities of genes implicated in familial cancer, tumor progression, and the 5-fluorouracil pathway were common but were not associated with specific types of pancreatic cancer.5FU = 5-fluorouracil; FISH = fluorescence in situ hybridization; ND-FISH = interphase FISH to detect abnormalities of chromosome number and structure; SSC = standard saline citratePancreatic cancer afflicts more than 200,000 new patients worldwide each year, including more than 37,600 in the United States.^1-4 Surgery seldom cures pancreatic cancer and effective chemotherapies are largely unknown.⁵ Survival varies among patients with pancreatic cancer but is often measured in months.^6,7 Thus, novel genetic research of pancreatic cancer is urgently needed to help establish accurate diagnoses and to develop effective treatments for this important public health problem.This investigation used fluorescence in situ hybridization (FISH) to visualize chromosomal loci in interphase nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas. Acinar cell carcinoma and ductal adenocarcinoma, which are nonendocrine tumors, and islet cell carcinomas, which are neuroendocrine tumors, reportedly occur in less than 1%, 95%, and 5%, respectively, of patients with pancreatic cancer.^3,8,9 In 2 retrospective studies of large series of patients, median survival for unresected ductal adenocarcinoma was 3 months⁸; for unresected acinar cell carcinoma, 25 months⁸; for nonfunctional islet cell carcinoma, 26 months⁹; and for functional islet cell carcinoma, 54 months.⁹Although some genetic studies of pancreatic cancer have been published, most focus on ductal adenocarcinoma. An assortment of genetic procedures have been attempted to investigate pancreatic cancer, including family history studies,¹ conventional cytogenetic techniques,¹⁰ interphase FISH,^11-13 comparative genomic hybridization,¹⁴ RNA expression analyses,^15,16 and evaluation of sequence variations.¹⁷ These studies implicate a variety of point mutations and chromosomal anomalies in most, if not all, patients with pancreatic cancer. Nevertheless, the biology of various forms of pancreatic cancer remains poorly understood, and this problem precludes efforts to establish novel genetic treatments for these disorders.This investigation used interphase FISH to visualize genetic abnormalities in individual normal and neoplastic cells in acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.¹⁸ This research project was specifically designed to detect genetic abnormalities that have been shown via other genetic technologies to be associated with acinar cell carcinoma of the pancreas, familial pancreatic cancer, tumor progression in pancreatic cancer, or genes linked with the molecular pathway of 5-fluorouracil (5FU) chemotherapy.     

The association of active cancer with venous thromboembolism location: a population-based study

OBJECTIVE: To test active cancer for an association with venous thromboembolism (VTE) location.PATIENTS AND METHODS: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN, residents with incident VTE during the 35-year period 1966-2000 (N=3385). We restricted analyses to residents with objectively diagnosed VTE during the 17-year period from January 1, 1984, to December 31, 2000 (N=1599). For each patient, we reviewed the complete medical records in the community for patient age, gender, and most recent body mass index at VTE onset; VTE event type and location; and previously identified independent VTE risk factors (ie, surgery, hospitalization for acute medical illness, active cancer, leg paresis, superficial venous thrombosis, and varicose veins). Using logistic regression we tested active cancer for an association with each of 4 symptomatic VTE locations (arm or intra-abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism, and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE risk factors.RESULTS: In multivariate analyses, active cancer was independently associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P=.01), intra-abdominal DVT (OR, 2.22; P=.004), and bilateral leg DVT (OR, 2.09; P=.02), but not pulmonary embolism (OR, 0.93).CONCLUSION: Active cancer is associated with VTE location. Location of VTE may be useful in decision making regarding cancer screening.BMI = body mass index; CI = confidence interval; CTEPH = chronic thromboembolic pulmonary hypertension; DVT = deep venous thrombosis; OR = odds ratio; PE = pulmonary embolism; VTE = venous thromboembolismThe association between cancer and venous thromboembolism (VTE) is well-established and strong.^1-4 Active cancer with and without chemotherapy increases VTE risk by 5- to 6-fold.⁵ Furthermore, active cancer accounts for about 20% of the entire VTE burden occurring in a community.⁶ Indeed, VTE is the second most common cause of death among patients with cancer.⁷ Cancer patients with VTE have a 2-fold or greater increase in mortality compared with cancer patients without VTE, even after adjusting for stage.^8,9 Nearly half of the patients with cancer-associated VTE have distant metastases at the time of VTE diagnosis.⁸ The incidence of cancer in patients with recurrent idiopathic VTE is higher than that in patients with secondary VTE.³Opinions differ regarding screening for an underlying occult cancer after an idiopathic VTE event.^10,11 Although a small randomized clinical trial found that more occult cancers were detected at an early stage with extensive screening, which theoretically could improve cancer treatment potential, no difference in survival was noted between this strategy and usual care.¹⁰ Because anticoagulant therapy improves the outcomes of patients with VTE and cancer, it is still important to recognize which patients with VTE have an underlying active cancer.¹² The diagnosis of VTE may help to uncover previously occult cancer by prompting a complete physical examination and testing consistent with standard health care maintenance. However, indiscriminate cancer screening is not cost-effective.^13,14 To provide a more organized and cost-effective approach to cancer detection among patients with VTE, the VTE characteristics associated with cancer must be recognized. Although evidence shows that idiopathic VTE and bilateral deep venous thrombosis (DVT) correlate with subsequent cancer diagnosis,^3,15 there is a paucity of data regarding the association between active cancer and VTE location. The current study aims to determine whether underlying cancer is associated with particular VTE locations.     

A prospective study of fasting plasma glucose and risk of stroke in asymptomatic men

OBJECTIVE: To examine the association between levels of fasting plasma glucose (FPG) and incidence of stroke outcomes in a large cohort of asymptomatic men.PATIENTS AND METHODS: Participants were 43,933 men (mean ± SD age, 44.3±9.9 years) who were free of known cardiovascular disease at baseline and whose FPG levels were assessed during a preventive medical examination at the Cooper Clinic, Dallas, TX, between January 7, 1971, and March 11, 2002. Patients with diagnosed diabetes mellitus (DM) or low FPG (<80 mg/dL [to convert to mmol/L, multiply by 0.0555]) were excluded. Fatal stroke was identified through the National Death Index, and nonfatal stroke was ascertained from mail-back surveys.RESULTS: A total of 595 stroke events (156 fatal and 456 nonfatal strokes; 17 men reported a nonfatal stroke before they died of stroke) occurred during 702,928 person-years of exposure. Age-adjusted fatal, nonfatal, and total stroke event rates per 10,000 person-years for normal FPG (80-109 mg/dL), impaired fasting glucose (110-125 mg/dL), and undiagnosed DM (≥126 mg/dL) were 2.1, 3.4, and 4.0 (P_trend=.002); 10.3, 11.8, and 18.0 (P_trend=.008); and 8.2, 9.6, and 12.4 (P_trend=.008), respectively. After further adjusting for potential confounders, the direct association between FPG and fatal, nonfatal, or total stroke events remained significant (P_trend=.02, .03, and .01, respectively). For FPG levels of 110 mg/dL or greater, each 10-unit increment of FPG was associated with a 6% higher risk of total stroke events (P=.05).CONCLUSION: Hyperglycemia (FPG, ≥110 mg/dL), even below the DM threshold (such as with impaired fasting glucose), was associated with a higher risk of fatal, nonfatal, or total stroke events in asymptomatic men.ACLS = Aerobics Center Longitudinal Study; ADA = American Diabetes Association; BMI = body mass index; CI = confidence interval; CVD = cardiovascular disease; DM = diabetes mellitus; ECG = electrocardiography; FPG = fasting plasma glucose; ICD = International Classification of Diseases; IFG = impaired fasting glucose; MetS = metabolic syndrome; NDI = National Death IndexThe primary causes of death and disability in patients with diabetes mellitus (DM) are cardiovascular and cerebrovascular complications.^1-5 Previous studies have reported an independent and direct association of clinically diagnosed DM and stroke^2,5-7; however, about half of all patients with type 2 DM are undiagnosed because they remain asymptomatic for long periods.⁸ Those with undiagnosed DM often have elevated levels of fasting plasma glucose (FPG) but no symptoms of DM. To date, few studies have examined the effect of FPG on stroke events, and the findings are inconclusive.^6,9-13 Some have reported a positive association between elevated FPG levels and stroke,^9,10 whereas others failed to identify impaired glucose levels as a significant risk predictor for stroke.^6,11-13 The inconsistent findings may be due to differences in study populations, length of follow-up, stroke outcome definition (such as fatal, nonfatal, or a combination), confounders selection, or a combination of these factors.For editorial comment, see page 1038In 2003, the American Diabetes Association (ADA) recommended changing the lower limit for the diagnosis of impaired fasting glucose (IFG) from 110 to 100 mg/dL (to convert to mmol/L, multiply by 0.0555).¹⁴ However, the need for this change has since been questioned, and concerns have been raised regarding the potential public health implications.^15-18 Therefore, we used the widely accepted 1997 ADA guidelines¹⁹ to define the IFG (FPG, 110-125 mg/dL) and DM (FPG, ≥126 mg/dL). We evaluated the association between FPG (including undiagnosed DM and IFG, as well as lower levels of FPG [100-109 mg/dL]) and fatal, nonfatal, and fatal/nonfatal combined stroke in a large cohort of men while controlling for cardiorespiratory fitness, an independent predictor of mortality and morbidity.^20,21     

Bacteria on Catheters in Patients Undergoing Peritoneal Dialysis

♦ Background: Peritonitis is the leading cause of morbidity for peritoneal dialysis (PD) patients, and microbial biofilms have previously been identified on catheters from infected patients. However, few studies of catheters from patients without clinical signs of infection have been undertaken. The aim of the present study was to investigate the extent to which bacteria are present on catheters from PD patients with no symptoms of infection.♦ Methods: Microbiologic culturing under aerobic and anaerobic conditions and confocal laser scanning microscopy were used to determine the distribution of bacteria on PD catheters from 15 patients without clinical signs of infection and on catheters from 2 infected patients. The 16S rRNA gene sequencing technique was used to identify cultured bacteria.♦ Results: Bacteria were detected on 12 of the 15 catheters from patients without signs of infection and on the 2 catheters from infected patients. Single-species and mixed-microbial communities containing up to 5 species were present on both the inside and the outside along the whole length of the colonized catheters. The bacterial species most commonly found were the skin commensals Staphylococcus epidermidis and Propionibacterium acnes, followed by S. warneri and S. lugdunensis. The strains of these micro-organisms, particularly those of S. epidermidis, varied in phenotype with respect to their tolerance of the major classes of antibiotics.♦ Conclusions: Bacteria were common on catheters from patients without symptoms of infection. Up to 4 different bacterial species were found in close association and may represent a risk factor for the future development of peritonitis in patients hosting such micro-organisms.Key words: Biofilm, 16S rRNA gene sequencing, anaerobic culture, confocal microscopyThe advantages of peritoneal dialysis (PD) over hemodialysis are the higher relative freedom and the lower cost for patients, but the major drawback is the risk of infections such as peritonitis. Peritonitis gives rise to symptoms including abdominal pain and fever (1), and it is a leading cause of morbidity and technique failure in PD (2,3). The average incidence of peritonitis in the PD population varies considerably depending on factors such as country, center, PD technique, and patient category, ranging from more than 2 episodes per patient per year (4) to fewer episodes than 1 every 4th year (1). The organisms that most commonly cause peritonitis are coagulase-negative staphylococci (CoNS), including Staphylococcus epidermidis and S. aureus (2,5-8). However, infections involving gram-negative bacteria—for example, Klebsiella, Escherichia coli, Pseudomonas—or mixed populations are generally more severe, leading to more hospitalizations, catheter removals, PD dropouts, and deaths (8-11). Under microscopy, PD catheters removed from patients experiencing infections have been shown to be covered with microbial biofilms (12,13), consisting of single-species (14) or mixed-microbial populations (13,14). Despite the large number of potential niches in biofilms, medical device-associated biofilms often show a low degree of microbial diversity (15,16).Naturally, much work has been conducted in PD patients with infections, but only a few studies have investigated microbial biofilms on catheters from patients without clinical signs of infection, with results ranging from an absence of bacteria to lightly colonized areas and mature biofilms (12-14). The latter studies focused primarily on revealing the presence and surface coverage of biofilms rather than on identifying the bacterial species present, although cultures of catheter scrapings revealed S. epidermidis, S. aureus, and species of the Enterobacteriaceae family (12-14). Normally, analysis of dialysis effluent is used to isolate and identify bacteria in PD patients with infections (6,8,17), but how well effluent cultures correlate with what is actually on the catheter is not known, and studies of actual catheters are therefore important.We set out to identify the range of aerobic and anaerobic bacterial species on PD catheters from patients without infections and to compare those results with results obtained from catheters in PD patients with infections. We also studied the phenotypic variation of the bacterial strains isolated. Data presented here show bacterial colonization, commonly by skin commensals, on most catheters. Bacteria were found in single-organism or mixed-microbial populations that showed a varied phenotypic pattern of antibiotic tolerance.     

Colonic polyposis and neoplasia in Cowden syndrome

OBJECTIVE: To identify and describe the frequency, histologic features, and clinical outcome of colon polyposis and neoplasia in Cowden syndrome—a rare familial hamartoma tumor syndrome associated with mutations in the PTEN gene.PATIENTS AND METHODS: Patients with a clinical diagnosis of PTEN hamartoma tumor syndrome-Cowden phenotype were retrospectively identified and studied. Only those who underwent colonoscopy or colon pathologic interpretation were included in the final analysis.RESULTS: From 1994 to 2009, 13 patients met study inclusion criteria. Of the 10 patients who underwent colonoscopy, 9 (90%; 95% confidence interval [CI], 57%-100%) had polyps, and 7 (70%; 95% CI, 39%-90%) were estimated to have more than 50 polyps. Pathologic findings of the colon were reviewed in 11 patients, and the spectrum of tumors included hamartomatous, inflammatory, adenomatous, ganglioneuromatous, hyperplastic, and juvenile polyps. Of the 13 patients, 2 (15%; 95% CI, 3%-43%) had left-sided adenocarcinoma without microsatellite instability. Five (38%) of the 13 patients underwent colectomy secondary to polyp dysplasia.CONCLUSION: Patients with Cowden syndrome have a heavy colon polyp burden with a wide pathologic spectrum, both benign and malignant. The colon polyposis results in a previously unreported morbidity with a high colectomy rate.AJCC = American Joint Committee on Cancer; CI = confidence interval; CS = Cowden syndrome; GI = gastrointestinal; NCCN = National Comprehensive Cancer Network; PHTS = PTEN hamartoma tumor syndromeThe PTEN hamartoma tumor syndrome (PHTS) is a spectrum of autosomal dominant clinical disorders associated with mutations of the PTEN or phosphatase and tensin homolog gene on chromosome 10.^1,2 Cowden syndrome (CS) is the most common phenotype, with an estimated incidence of 1 in 200,000 to 250,000 people.³ The pathognomonic features of CS are mucocutaneous and include trichilemmomas, acral keratoses, and papillomatous lesions. Patients with CS also have a high risk of thyroid, breast, and endometrial neoplasms.⁴ Gastrointestinal (GI) polyposis is a common manifestation and can occur throughout the entire tract; however, the frequency of colon involvement in patients with CS is unclear.⁵Cowden syndrome is classified as a hamartomatous polyposis syndrome—hamartomas being disorganized overgrowths of cells and tissue native to the anatomic location in which they occur. In the GI tract, these include both epithelial and stromal proliferations. Hamartomatous colon polyps, which can histologically resemble juvenile or Peutz-Jeghers polyps, are thought to predominate in CS. However, a wide variety of other polyp histologic findings have been described, including adenomatous, inflammatory, hyperplastic, lymphoid, ganglioneuromatous, and leiomyomatous polyps.^6-8 Despite reports of multiple colon polyp histologic diagnoses from single patients,^9,10 it is uncertain whether this is a common phenomenon.¹¹Traditionally, patients with CS have not been considered to have an increased risk of colorectal cancers.^6,12 This impression has started to change. Several case reports have described colorectal cancer in CS, including one describing multiple colorectal cancers in a single patient.^13-15 A recent study of a multicenter cohort of PTEN mutation carriers reported 13% with colorectal cancer; all affected patients were younger than age 50 years.¹⁶ Furthermore, a recent compilation of cases reported a 16% (95% confidence interval [CI], 8%-24%) lifetime colorectal cancer risk in patients with CS.¹⁷The uncertainty of the prevalence and risks of colorectal polyposis in patients with CS is reflected in the lack of recommendations regarding colorectal screening or surveillance in the National Comprehensive Cancer Network (NCCN) treatment guidelines.¹⁸ The purpose of this study was to investigate the spectrum of colon disease in patients with CS, with special emphasis on polyp frequency, histopathologic findings, and clinical outcomes.     

Incidence of Invasive Pneumococcal Disease Among Children After Introduction of a 7-Valent Pneumococcal Conjugate Vaccine: A Population-Based Study in Olmsted County, Minnesota

OBJECTIVE: To examine the effect of the 7-valent pneumococcal conjugate vaccine in a well-characterized population in Olmsted County, Minnesota, with a combination of urban and rural residents likely to have a relatively low risk of invasive pneumococcal disease (IPD).PATIENTS AND METHODS: This population-based study analyzed data from children younger than 5 years to determine the incidence of IPD from January 1, 1995, to December 31, 2007.RESULTS: From 1995 through 2007, 29 cases of IPD were identified in the study population, but 2 patients denied research authorization; thus, 27 cases were available for review. From 1995-1999 to 2001-2003, the incidence of IPD decreased from 33.5 (95% confidence interval [CI], 16.6-50.5) to 10.8 (95% CI, 0.0-23.0) cases per 100,000 person-years (68% decrease; P=.046). The incidence subsequently increased to 15.2 (95% CI, 3.0-27.4) cases per 100,000 person-years from 2004 through 2007; however this change was not significant (P=.62). All cases of IPD with available serotype data from 2002 through 2007 (n=5) were due to non-7-valent conjugate vaccine serotypes.CONCLUSION: Although the baseline incidence of IPD was much lower than that reported in other populations, the overall incidence of IPD decreased significantly in children younger than 5 years after introduction of a 7-valent conjugate vaccine.CDC = Centers for Disease Control and Prevention; CI = confidence interval; IPD = invasive pneumococcal disease; MIC = minimum inhibitory concentration; PCV-7 = 7-valent pneumococcal conjugate vaccineAfter the introduction of a 7-valent pneumococcal conjugate vaccine (PCV-7) for children in early 2000 in the United States, the incidence of invasive pneumococcal disease (IPD) decreased substantially in several populations in the United States.^1-7 These populations included metropolitan areas throughout the United States (Active Bacterial Core Surveillance),¹ a health care system in Northern California (Kaiser Permanente),² 8 children''s hospitals in the United States (US Pediatric Multicenter Pneumococcal Surveillance Group),³ the state of Alaska (Arctic Investigations Program),⁴ the metropolitan Atlanta area (Georgia Emerging Infections Program),⁵ and a White Mountain Apache tribe in northern Arizona.⁷ The baseline incidence of IPD among children younger than 5 years in these populations ranged from 62.5 cases per 100,000 in the Kaiser Permanente population,² to 96.4 cases per 100,000 in the metropolitan areas of the Active Bacterial Core Surveillance population,¹ to 139.7 cases per 100,000 in metropolitan Atlanta,⁵ to 473 cases per 100,000 in the White Mountain Apache tribe.⁷To examine the effect of PCV-7 in a well-characterized population in the midwestern United States with a combination of urban and rural residents likely to have a relatively low risk of IPD,⁸ we conducted a population-based incidence study of IPD in Olmsted County, Minnesota, from 1995 through 2007.     

Geriatric Nutritional Risk Index as a Prognostic Factor in Peritoneal Dialysis Patients

♦ Background: The Geriatric Nutritional Risk Index (GNRI) might be a useful screening tool for malnutrition in dialysis patients. However, data concerning the GNRI as a prognostic factor in peritoneal dialysis (PD) patients are scarce.♦ Methods: We reviewed the medical records at Yeungnam University Hospital in Korea to identify all adults (>18 years) who received PD; 486 patients were enrolled in the study.♦ Results: The initial low, middle, and high GNRI tertiles included 162, 166, and 158 patients respectively. Significant correlations were noted between the initial GNRI and body mass index, creatinine, albumin, arm circumference, fat mass index, and comorbidities. The cut-off value for the time-averaged GNRI over 1 year was 96.4, and the sensitivity and specificity for a diagnosis of a decline in lean mass were 77.1% and 40.0% respectively. A multivariate analysis adjusted for age, risk according to the Davies comorbidity index, and C-reactive protein showed that an low initial GNRI tertile was associated with mortality in PD patients.♦ Conclusions: The GNRI is a simple method for predicting nutrition status and clinical outcome in PD patients.Key words: Geriatric Nutritional Risk Index, prognostic factor, nutrition, lean massMalnutrition is one of the most common complications encountered in dialysis patients. Depending on the method used to assess nutrition status, the prevalence of malnutrition ranges from 18% to 70% in maintenance dialysis patients (1). Development of malnutrition is associated with dialysis-related factors such as bioincompatibility and unrelated factors such as comorbidities (1,2). Furthermore, studies have linked malnutrition with prognosis in dialysis patients (1-4).The methods for evaluating nutrition status in dialysis patients involve the use of biochemical markers, creatinine kinetics, anthropometric measurements, body composition analyses, and questionnaires (1,2). Biochemical markers such as albumin are the most commonly used markers of nutrition in dialysis patients; however, those markers are affected by various conditions—for example, inflammation and hydration status (1,5). Anthropometric measurements such as body mass index (BMI) cannot distinguish between lean mass and fat or bone (6). Measurement of body composition provides an objective assessment, but it requires expensive equipment.Bouillanne et al. (7) first reported the validity of the Geriatric Nutritional Risk Index (GNRI) for malnutrition screening in elderly patients. The GNRI has both anthropometric and biochemical components (7-9). Some studies demonstrated the usefulness of the GNRI as a new marker for malnutrition screening in dialysis patients (8,9). However, few reports have assessed the effectiveness of the GNRI as a prognostic factor in peritoneal dialysis (PD) patients. The aim of the present study was to evaluate the clinical relevance and usefulness of the GNRI as a prognostic factor in PD patients.     

Obesity Paradox and Cardiorespiratory Fitness in 12,417 Male Veterans Aged 40 to 70 Years

OBJECTIVE: To evaluate the influence of cardiorespiratory fitness (fitness) on the obesity paradox in middle-aged men with known or suspected coronary artery disease.PATIENTS AND METHODS: This study consists of 12,417 men aged 40 to 70 years (44% African American) who were referred for exercise testing at the Veterans Affairs Medical Centers in Washington, DC, or Palo Alto, CA (between January 1, 1983, and June 30, 2007). Fitness was quantified as metabolic equivalents achieved during a maximal exercise test and was categorized for analysis as low, moderate, and high (defined as <5, 5-10, and >10 metabolic equivalents, respectively). Adiposity was defined by body mass index (BMI) according to standard clinical guidelines. Separate and combined associations of fitness and adiposity with all-cause mortality were assessed by Cox proportional hazards analyses.RESULTS: We recorded 2801 deaths during a mean ± SD follow-up of 7.7±5.3 years. Multivariate hazard ratios (95% confidence interval) for all-cause mortality, with normal weight (BMI, 18.5-24.9 kg/m²) used as the reference group, were 1.9 (1.5-2.3), 0.7 (0.7-0.8), 0.7 (0.6-0.7), and 1.0 (0.8-1.1) for BMIs of less than 18.5, 25.0 to 29.9, 30.0 to 34.9, and 35.0 or more kg/m², respectively. Compared with highly fit normal-weight men, underweight men with low fitness had the highest (4.5 [3.1-6.6]) and highly fit overweight men the lowest (0.4 [0.3-0.6]) mortality risk of any subgroup. Overweight and obese men with moderate fitness had mortality rates similar to those of the highly fit normal-weight reference group.CONCLUSION: Fitness altered the obesity paradox. Overweight and obese men had increased longevity only if they registered high fitness.BMI = body mass index; BP = blood pressure; CI = confidence interval; CVD = cardiovascular disease; HR = hazard ratio; MET = metabolic equivalent; VETS = Veterans Exercise Testing StudyBody mass index (BMI) has been widely used to evaluate the mortality risk associated with obesity. Although many large epidemiological studies of the general population report a positive association between BMI and mortality,^1-3 consistent inverse associations (the so-called obesity paradox) have been observed among patients with heart failure,⁴ coronary heart disease,^5,6 hypertension,⁷ peripheral artery disease,⁸ type 2 diabetes,⁹ and chronic kidney disease.¹⁰ An obesity paradox has also been observed in healthier populations as diverse as San Francisco longshoremen,¹¹ Native American women of the Pima tribe,¹² men from rural Scotland,¹³ Nauruan men,¹⁴ and the elderly.¹⁵Although substantial evidence for an obesity paradox has accumulated during the past decade,¹⁶ including a recent examination of the influence of weight loss,¹⁷ the influence of cardiorespiratory fitness (fitness) has not been adequately explored. Objective measures of fitness from clinical exercise testing are not readily available. Consequently, few studies have examined the combined effects of fitness and BMI on mortality, and these data come from only 2 cohorts: the Lipid Research Clinics Study^18,19 and the Aerobics Center Longitudinal Study.^20-26 Collectively, these reports provide convincing evidence that fitness is a more powerful predictor of mortality than BMI. However, these findings are from populations without an obesity paradox.For editorial comment, see page 112The Veterans Exercise Testing Study (VETS) affords a unique opportunity to study simultaneous measures of fitness and adiposity in a large patient population exhibiting an obesity paradox. A previous report from our group provided compelling evidence that higher levels of fitness, as well as higher BMI, reduced mortality risk in men referred for exercise testing.²⁷ However, this report did not examine the combined effects of fitness and BMI on mortality. Such joint analyses may identify associations obscured in independent analyses alone. To avoid bias associated with age,²⁸ we confined our investigation to men aged 40 to 70 years. The purpose of the current study was to examine the influence of fitness on the obesity paradox in middle-aged men with known or suspected cardiovascular disease (CVD).     

A Comparison of Long- and Short-Acting Opioids for the Treatment of Chronic Noncancer Pain: Tailoring Therapy to Meet Patient Needs

Management of chronic noncancer pain (CNCP) requires a comprehensive assessment of the patient, the institution of a structured treatment regimen, an ongoing reassessment of the painful condition and its response to therapy, and a continual appraisal of the patient''s adherence to treatment. For many patients with CNCP, the analgesic regimen will include opioids. Physicians should consider the available evidence of efficacy, the routes of administration, and the pharmacokinetics and pharmacodynamics of the various formulations as they relate to the temporal characteristics of the patient''s pain. When making initial decisions, physicians should decide whether to prescribe a short-acting opioid (SAO) with a relatively quick onset of action and short duration of analgesic activity, a long-acting opioid (LAO) with a longer duration of analgesic action but a potentially longer onset of action, or both. Studies suggest that SAOs and LAOs are both effective for most types of CNCP. A review of published studies found no data to suggest that either SAOs or LAOs are generally more efficacious for treating any particular CNCP condition. The LAOs may provide more stable analgesia with less frequent dosing; however, opioid therapy should be tailored to the pain state and the individual patient, and SAOs may be appropriate for some patients with CNCP. MEDLINE and PubMed searches were conducted to locate relevant studies published from January 1975 to April 2008 using the following search terms: opioids, short-acting opioids, long-acting opioids, chronic pain, chronic pain AND opioids, and narcotics. English-only randomized controlled trials and nonrandomized studies were considered.ADL = activities of daily living; AE = adverse effect; ATC = around-the-clock; BPI = Brief Pain Inventory; CNCP = chronic noncancer pain; CR = controlled-release; DN = diabetic neuropathy; ER = extended-release; IR = immediate-release; LAO = long-acting opioid; LBP = low back pain; NSAID = nonsteroidal anti-inflammatory drug; PHN = postherpetic neuralgia; QOL = quality of life; SAO = short-acting opioid; SNRI = serotonin norepinephrine reuptake inhibitor; SR = sustained-release; TCA = tricyclic antidepressantThe International Association for the Study of Pain defines chronic pain as persistent pain lasting longer than the time required for normal tissue healing; for chronic noncancer pain (CNCP), this is generally defined as 3 months or longer.^1,2 Chronic pain affects an estimated 75 million people in the United States and is the nation''s leading cause of disability.³ Individuals with chronic pain may also experience depression, impaired sleep, and a diminished ability to perform normal activities of daily living (ADLs).^4,5 Chronic pain conditions have a substantial financial impact, accounting for an estimated annual total economic loss of $100 billion (in 1998 dollars),⁶ including $61.2 billion attributed to lost workplace productivity.⁷Management of chronic pain often requires a multimodal approach that integrates pharmacological and nonpharmacological treatments, such as rehabilitative measures and interventional techniques.⁸ Many single-agent or combination pharmacological options for CNCP treatment are available, including nonselective and cyclooxygenase 2-specific nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, anticonvulsant agents, antidepressant agents, local anesthetics, α₂-adrenergic agonists, and opioids.⁸ Opioids often are used to manage moderate to severe CNCP^9-11 and are particularly advantageous because they are effective for many types of CNCP.⁹ No evidence indicates that long-term use of single-agent opioid analgesic preparations results in end-organ failure, as may be seen with other analgesics (eg, NSAIDs), or with certain combination opioid analgesics.¹² In addition to their role in the management of cancer pain, opioids are recommended for the treatment of select patients with a variety of CNCP conditions, several of which are discussed in this review.^13-17 For example, opioids may be used in patients with chronic low back pain (LBP) who do not respond adequately to mild analgesic agents, such as acetaminophen or NSAIDs.¹⁵ Opioids are recommended for various neuropathic pain states, particularly if trials of gabapentin, pregabalin, tricyclic antidepressants (TCAs), and/or serotonin norepinephrine reuptake inhibitors (SNRIs) fail to provide adequate analgesia.^18-20A recent review of available data on the management of osteoarthritis led to a recommendation for weak opioids (eg, tramadol) when pain is refractory to treatment with nonopioid pharmacological approaches (eg, acetaminophen, NSAIDs, injected corticosteroids) or when these agents are contraindicated; stronger opioids (eg, oxycodone, morphine) are recommended for the management of severe osteoarthritis-related pain that adversely affects patients'' quality of life (QOL).²¹For editorial comment, see page 572To develop this comparison between short-acting opioids (SAOs) and long-acting opioids (LAOs), we searched the MEDLINE and PubMed databases for relevant studies published from January 1975 to April 2008 using the following search terms: opioids, short-acting opioids, long-acting opioids, chronic pain, chronic pain AND opioids, and narcotics. Only randomized controlled trials and nonrandomized studies published in English were considered.Opioid formulations have been classified as short- or long-acting on the basis of their duration of action. The SAOs are distinguished from LAOs by a more rapid increase and decrease in serum levels; LAOs are formulated to release drug more gradually into the bloodstream or have a long half-life for prolonged activity.²² Generally, SAOs are considered appropriate for transient pain types, such as acute, breakthrough, or chronic intermittent pain, which do not require long-lasting analgesia.^22-24 Commonly prescribed SAOs include immediate-release (IR) morphine, hydromorphone, oxymorphone, codeine, fentanyl, hydrocodone, and oxycodone²²; codeine, hydrocodone, and oxycodone are also available in combination with acetaminophen or an NSAID,^25-28 which limits the maximum daily dose because of the risk of liver and gastrointestinal toxic effects. This ceiling effect, which is related only to the nonopioid component, may prevent titration to an adequate opioid analgesic dose.²² However, these risks of toxic effects have not been shown to reduce misuse and abuse of these agents.The LAO analgesic effect is generally more prolonged than that of SAOs.^23,29-33 Some LAOs (eg, methadone, levorphanol) are inherently pharmacologically long acting (32 whereas others, such as extended-release (ER), sustained-release (SR), or controlled-release (CR) formulations of oxycodone,²⁹ oxymorphone,³³ fentanyl,³⁵ and morphine,³⁰ have been modified to temporally extend the release of drug into the bloodstream. The analgesic effects of LAOs generally last 8 to 72 hours,²² making them appropriate for patients with persistent CNCP that requires stable, around-the-clock (ATC) dosing.^22,36 Open in a separate window     

Patients Dismissed From the Hospital With a Diagnosis of Noncardiac Chest Pain: Cardiac Outcomes and Health Care Utilization

OBJECTIVE: To determine the proportion of patients with noncardiac chest pain (NCCP) who see a gastroenterologist, the type and frequency of gastrointestinal (GI) and cardiac tests performed, and the frequency of cardiac death.PATIENTS AND METHODS: A cohort of Olmsted County, Minnesota, residents presenting to the emergency department (ED) with chest pain between January 1, 1985, and December 31, 1992, was identified through the Rochester Epidemiology Project. We assessed the frequency of ED, cardiology, and gastroenterology visits and corresponding tests after a diagnosis of NCCP (n=320). We also assessed the frequency of cardiac events.RESULTS: During follow-up, 49% of patients sought care in the ED, 42% had repeated cardiology evaluations, and 15% were seen by a gastroenterologist. Thirty-eight percent underwent esophagogastroduodenoscopy, but very few underwent manometry or a pH probe. Patients with NCCP of unknown origin had 3 times the rate of GI consultations as their counterparts with a GI disorder. Survival free of cardiac death in the subset with NCCP with a GI disorder was 90.2% at 10 years and 84.8% at 20 years, compared with 93.7% at 10 years and 88.1% at 20 years for the subset with NCCP of unknown origin.CONCLUSION: The frequency of health care utilization in NCCP patients is high, but relatively few GI consultations and even fewer GI tests are performed. Patients dismissed from the hospital with NCCP continue to experience cardiac events, which may highlight a need for more aggressive cardiovascular risk factor management in this population.CABG = coronary artery bypass graft; CI = confidence interval; ED = emergency department; EGD = esophagogastroduodenoscopy; GERD = gastroesophageal reflux disease; GI = gastrointestinal; MI = myocardial infarction; NCCP = noncardiac chest pain; NCCP-GI = NCCP secondary to GI diagnoses; NCCP-U = NCCP of unknown originIn 2005, the American Heart Association estimated that 80 million Americans have cardiovascular disease.¹ The magnitude of this number has impelled patients and physicians to consider acute chest pain as a harbinger for impending myocardial infarction (MI) and potential death. Along with heightened sensitivity to the evaluation of chest pain has come increasing evidence that a significant proportion of individuals with chest pain have noncardiac chest pain (NCCP).² Noncardiac chest pain is defined by substernal chest pain in the absence of significant epicardial coronary artery stenoses. Previous population-based studies have reported the prevalence of this entity to be 23%.³Noncardiac chest pain is attributed to a variety of disorders, including gastroesophageal reflux disease (GERD) and esophageal hypersensitivity,⁴ panic attack,⁵ musculoskeletal pain,⁶ and microvascular disease (cardiac syndrome X).⁷ GERD is the most prevalent cause of NCCP, accounting for up to 60% of cases.^8-12 The prevalence of GERD in NCCP has been studied by pH monitoring and found to be 41% to 43%.^13,14The cost of evaluation of NCCP is estimated to be between $315 million and $1.8 billion per year.^4,15 The economic impact is further illustrated by a hospital-based prospective study that reported more frequent health care visits by patients with NCCP than by those with ischemic heart disease.¹⁶ Therefore, determining whether subgroups of patients with NCCP use more health care resources than others is important.For editorial comment, see page 309Although it is thought that patients with NCCP have a good prognosis, there is a paucity of data to support this conclusion. A few studies report that patients with normal findings on coronary angiography have minimal cardiac morbidity and mortality.^16,17 However, some studies point to increased cardiac mortality. A 16-year cohort study by Wilhelmsen et al¹⁸ found that men with nonspecific chest pain and normal findings on cardiac evaluation ultimately have high cardiovascular and noncardiovascular mortality rates. No large, long-term community studies have recorded the frequency of cardiac deaths that occur after a diagnosis of NCCP.We identified patients with a diagnosis of NCCP to determine the frequency of gastrointestinal (GI) consultations and testing and to identify the frequency of cardiac death.