Effect of a multiple-site intensive care unit telemedicine program on clinical and economic outcomes: an alternative paradigm for intensivist staffing

OBJECTIVE: To examine whether a supplemental remote intensive care unit (ICU) care program, implemented by an integrated delivery network using a commercial telemedicine and information technology system, can improve clinical and economic performance across multiple ICUs. DESIGN: Before-and-after trial to assess the effect of adding the supplemental remote ICU telemedicine program. SETTING: Two adult ICUs of a large tertiary care hospital. PATIENTS: A total of 2,140 patients receiving ICU care between 1999 and 2001. INTERVENTIONS: The remote care program used intensivists and physician extenders to provide supplemental monitoring and management of ICU patients for 19 hrs/day (noon to 7 am) from a centralized, off-site facility (eICU). Supporting software, including electronic data display, physician note- and order-writing applications, and a computer-based decision-support tool, were available both in the ICU and at the remote site. Clinical and economic performance during 6 months of the remote intensivist program was compared with performance before the intervention. MEASUREMENTS AND MAIN RESULTS: Hospital mortality for ICU patients was lower during the period of remote ICU care (9.4% vs. 12.9%; relative risk, 0.73; 95% confidence interval [CI], 0.55-0.95), and ICU length of stay was shorter (3.63 days [95% CI, 3.21-4.04] vs. 4.35 days [95% CI, 3.93-4.78]). Lower variable costs per case and higher hospital revenues (from increased case volumes) generated financial benefits in excess of program costs. CONCLUSIONS: The addition of a supplemental, telemedicine-based, remote intensivist program was associated with improved clinical outcomes and hospital financial performance. The magnitude of the improvements was similar to those reported in studies examining the impact of implementing on-site dedicated intensivist staffing models; however, factors other than the introduction of off-site intensivist staffing may have contributed to the observed results, including the introduction of computer-based tools and the increased focus on ICU performance. Although further studies are needed, the apparent success of this on-going multiple-site program, implemented with commercially available equipment, suggests that telemedicine may provide a means for hospitals to achieve quality improvements associated with intensivist care using fewer intensivists.     

Familial Nephropathic Non-neuropathic Amyloidosis: Clinical Features, Immunohistochemistry and Chemistry

Classification of familial amyloidosis by the chemical natureof the fibrillar protein has become possible. Most such amyloidogenicproteins so far recognized are variant transthyretins, but twokindreds with the same apolipoprotein AI modification have beenreported. We describe the clinical features of another suchfamily in whom petechial skin rash appeared to be a marker forthe disease, which was non-neuropathic and of the Ostertag-type.Immunohistochemistry showed the protein to be apolipoproteinAI, but allele-specific DNA amplification indicated that itwas not the Arg²⁶ variant previously identified.     

alpha(2C)-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy.

The alpha(2A)-adrenergic receptor (AR) subtype mediates antinociception induced by the alpha(2)AR agonists clonidine, dexmedetomidine, norepinephrine, and 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK-14,304) as well as antinociceptive synergy of UK-14,304 with opioid agonists [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin and deltorphin II. Differential localization of alpha(2)-adrenergic (alpha(2A)-, alpha(2B)-(,) alpha(2C)-) and opioid (mu-, delta-, kappa-) subtypes suggests differential involvement of subtype pairs in opioid-adrenergic analgesic synergy. The present study applies a novel imidazoline(1)/alpha(2)-adrenergic receptor analgesic, moxonidine, to test for involvement of alpha(2B)- and alpha(2C)ARs in antinociception and antinociceptive synergy, because spinal antinociceptive activity of moxonidine shows minimal dependence on alpha(2A)AR. Intrathecal administration of moxonidine produced similar (2-3-fold) decreases in both mutant mice with a functional knockout of alpha(2A)AR (D79N-alpha(2A)AR) and alpha(2C)AR knockout (KO) mice. The potency of moxonidine was not altered in alpha(2B)KO mice, indicating that this subtype does not participate in moxonidine-induced spinal antinociception. Moxonidine-mediated antinociception was dose dependently inhibited by the selective alpha(2)-receptor antagonist SK&F 86466 in both D79N-alpha(2A) mice and alpha(2C)KO mice, indicating that alpha(2)AR activation is required in the absence of either alpha(2A)- or alpha(2C)AR. Spinal administration of antisense oligodeoxynucleotides directed against the alpha(2C)AR decreased both alpha(2C)AR immunoreactivity and the antinociceptive potency of moxonidine. Isobolographic analysis demonstrates that moxonidine-deltorphin antinociceptive synergy is present in the D79N-alpha(2A) mice but not in the alpha(2C)AR-KO mice. These results confirm that the alpha(2C)AR subtype contributes to spinal antinociception and synergy with opioids.     

UPBEAT: the impact of a psychogeriatric intervention in VA medical centers. Unified Psychogeriatric Biopsychosocial Evaluation and Treatment

BACKGROUND: The Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT) program provides individualized interdisciplinary mental health treatment and care coordination to elderly veterans whose comorbid depression, anxiety, or alcohol abuse may result in overuse of inpatient services and underuse of outpatient services. OBJECTIVES: To determine whether proactive screening of hospitalized patients can identify unrecognized comorbid psychiatric conditions and whether comprehensive assessment and psychogeriatric intervention can improve care while reducing inpatient use. DESIGN: Randomized trial. SUBJECTS: Veterans aged 60 and older hospitalized for nonpsychiatric medical or surgical treatment in 9 VA sites (UPBEAT, 814; usual care, 873). MEASURES: The Mental Health Inventory (MHI) anxiety and depression subscales, the Alcohol Use Disorder Identification Test (AUDIT) scores, RAND 36-Item Health Survey Short Form (SF-36), inpatient days and costs, ambulatory care clinic stops and costs, and mortality and readmission rates. RESULTS: Mental health and general health status scores improved equally from baseline to 12-month follow-up in both groups. UPBEAT increased outpatient costs by $1,171 (P <0.001) per patient, but lowered inpatient costs by $3,027 (P = 0.017), for an overall savings of $1,856 (P = 0.156). Inpatient savings were attributable to fewer bed days of care (3.30 days; P = 0.016) rather than fewer admissions. Patients with 1 or more pre-enrollment and postenrollment hospitalizations had the greatest overall savings ($6,015; P = 0.069). CONCLUSIONS: UPBEAT appears to accelerate the transition from inpatient to outpatient care for acute nonpsychiatric admissions. Care coordination and increased access to ambulatory psychiatric services produces similar improvement in mental health and general health status as usual care.     

Immunization with a recombinant MAGE-A3 protein after high-dose therapy for myeloma

MAGE-A3 is frequently expressed in high-risk multiple myeloma (MM). We immunized a healthy donor with MAGE-A3 protein formulated in AS02B to transfer immunity to her identical twin, diagnosed with MAGE-A3-positive MM. After a melphalan 200 mg/m syngeneic peripheral blood stem cell transplant, primed donor cells collected after immunizations were transferred and followed by repeated patient immunizations. MAGE-A3 immunizations were well tolerated. Strong MAGE-A3-specific antibody, cytotoxic T-lymphocyte (CTL), and T-helper responses were induced in both twins. A humoral response was transferred to the patient with the donor peripheral blood stem cells and increased by booster immunization. The CTL response targeted a previously undescribed HLA-A*6801 binding MAGE-A3115-123 peptide. MAGE-A3115-123 CTLs were detected in the patient more than 1 year after the last immunization. Multiple T-helper cellular responses were detected with the dominant response to an HLA-DR11 restricted MAGE-A3 epitope. The patient remains in remission 2.5 years after the second transplant. This report shows for the first time that immunization of a healthy donor with a defined cancer-testis protein induces immune responses that can be transferred and expanded posttransplant in the recipient. MAGE-A3 immunization may be a useful adjunct to high dose melphalan-based peripheral blood stem cell transplant, providing a new therapeutic option for high-risk MM.     

Serine proteases stimulate mucous glycoprotein release from hamster tracheal ring organ culture

The effects of several neurohumoral agents and serine proteases on glycoconjugate release from hamster tracheal organ cultures were assessed. The beta-adrenergic agonist isoproterenol inhibited glycoconjugate release, and its effect was abolished by the specific beta-blocking agent propranolol. A cholinergic agonist, pilocarpine, marginally increased glycoconjugate release, and its effect was abolished by the antagonist atropine. Human neutrophil elastase and porcine pancreatic trypsin consistently increased glycoconjugate release by 1.8 to 2.8-fold. When the proteases were inactivated, they were no longer effective in stimulating glycoconjugate release. Histologic and electron microscopic analysis of the protease-treated organ cultures revealed no discernible toxic reaction. In addition, organ cultures prelabeled with chromium 51 did not release an increased amount of radioactivity when treated with the proteases. Biochemical analysis of the glycoconjugates released into the culture medium showed them to be of high molecular weight (90% eluted in the void volume of a Sepharose 6B column) and to be resistant to digestion with hyaluronidase and heparinase, properties consistent with mucous glycoproteins. The mechanism of protease-induced glycoconjugate release is unknown. We speculate that stimulation of airway secretory cells by serine proteases of neutrophilic or other inflammatory cell origin may play a role in the increased airway secretion that is characteristic of acute tracheobronchitis.     

The ORION statement: guidelines for transparent reporting of outbreak reports and intervention studies of nosocomial infection

The quality of research in hospital epidemiology (infection control) must be improved to be robust enough to influence policy and practice. In order to raise the standards of research and publication, a CONSORT equivalent for these largely quasi-experimental studies has been prepared by the authors of two relevant systematic reviews, following consultation with learned societies, editors of journals and researchers. It consists of a 22 item checklist, and a summary table. The emphasis is on transparency to improve the quality of reporting and on the use of appropriate statistical techniques. The statement has been endorsed by a number of professional special interest groups and societies. Like CONSORT, ORION should be considered a 'work in progress', which requires ongoing dialogue for successful promotion and dissemination. The statement is therefore offered for further public discussion. Journals and research councils are strongly recommended to incorporate it into their submission and reviewing processes. Feedback to the authors is encouraged and the statement will be revised in 2 years.     

Cocaine-associated rhabdomyolysis and acute renal failure

We have described four male patients, aged 21 to 39 years, who had rhabdomyolysis and acute renal failure during parenteral cocaine use. This complication has only recently been attributed to cocaine. Their illnesses behaved clinically like nonoliguric acute tubular necrosis, though renal biopsies were not done. No permanent nerve, muscle, or kidney damage resulted.     

Improved liquid chromatographic/immunoassay of digoxin in serum

This HPLC/immunoassay procedure measures digoxin in serum with no interference from digoxin metabolites or digoxin-like factors. We used solid-phase (C18 and Diol) extraction, a C18 column with a tetrahydrofuran/water mobile phase, and final quantification by fluorescence polarization immunoassay. Deslanoside and gitoxigenin were used as the internal standard and the retention-time marker, respectively. The average CV for 300-microL samples at digoxin concentrations between 0.9 and 3.9 nmol/L was 9.3%. Minimum column lifetime with daily use was three months. We also compared results, for 49 samples from patients taking digoxin, obtained with the Abbott "TDx FPIA digoxin I" and the present procedure. Discrepancies between the two methods were substantial for 20% of the samples.