Alessandro Orlando

A randomized double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of two doses of the tramadol orally disintegrating tablet for the treatment of premature ejaculation within less than 2 minutes.

BACKGROUND Premature ejaculation (PE) is a widely observed male sexual dysfunction with a major impact on quality of life for many men and their sexual partners. OBJECTIVE To assess the safety of tramadol orally disintegrating tablet (ODT) (Zertane) and its efficacy in prolonging intravaginal ejaculation latency time (IELT) and improving Premature Ejaculation Profile (PEP) scores. DESIGN, SETTING, AND PARTICIPANTS We conducted an integrated analysis of two identical 12-wk randomized double-blind, placebo-controlled phase 3 trials across 62 sites in Europe. Healthy men 18-65 yr of age with a history of lifelong PE according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, and an IELT ≤ 120 s were included. There were 604 intent-to-treat subjects included in the analysis. INTERVENTION Subjects were randomized to receive 1:1:1 placebo (n=200), 62 mg tramadol ODT (n=206), or 89 mg tramadol ODT (n=198). MEASUREMENTS We measured overall change and fold increase in median IELT and the mean change in all four measures of the PEP. Differences across treatment groups were analyzed using Wilcoxon rank-sum tests, analysis of variance, and chi-square analyses. RESULTS AND LIMITATIONS Tramadol ODT resulted in significant increases in median IELT compared with placebo; increases were 0.6 min (1.6 fold), 1.2 min (2.4 fold), and 1.5 min (2.5 fold) for placebo, 62 mg tramadol ODT, and 89 mg tramadol ODT, respectively (p<0.001 for all comparisons). Men saw significantly greater improvement in all four measures of the PEP in both doses compared with placebo (p<0.05 for all comparisons). Tramadol ODT was well tolerated; study discontinuation occurred in 0%, 1.0%, and 1.6% of subjects in placebo, 62 mg, and 89 mg tramadol ODT groups, respectively. Limitations include study inclusion for men with IELT up to 120 s. CONCLUSIONS On-demand 62mg tramadol ODT is an effective treatment for PE in a low and safe therapeutic dose and provides a new option for managing mild to severe PE.

Outcomes of a nontransfer protocol for mild traumatic brain injury with abnormal head computed tomography in a rural hospital setting.

OBJECTIVE This study sought to investigate outcomes after a novel nontransfer protocol for mild traumatic brain injuries patients with small intracranial hemorrhage (ICH) in a rural trauma center without neurosurgical capabilities. METHODS This was a retrospective cohort study. In 2007, a nontransfer protocol was implemented at a Level III Trauma Center. It included adult patients from April 2007 through December 2012 with mild traumatic brain injury (mTBI) (Glasgow Coma Scale score 13 to 15) and computed tomography (CT) showing small ICH and no coagulopathy. The following ICHs were allowed: 1) minimal or small traumatic subarachnoid hemorrhage, 2) punctuate or minimal superficial cerebral contusion, 3) punctuate or minimal intraparenchymal hemorrhage, or 4) very small subdural hemorrhage (SDH) without mass effect (a very thin smear SDH along the tentorium or falx). CT scans were reviewed by the on-call neurosurgeon at an affiliated Level I Trauma Center, and consensus was obtained on the suitability for nontransfer. RESULTS A total of 76 patients were included. The median hospital length of stay was 1 day (interquartile range = 1 day). No patient required a neurosurgical intervention or postadmission transfer to a Level I facility. There were no in-hospital deaths, and all patients were discharged with stable head CTs and in good neurologic condition. Two patients were readmitted for nonprotocol-related reasons: 1 acute-on-chronic SDH 6 weeks postdischarge, and 1 visual eye change with normal CT 2 days postdischarge. CONCLUSIONS Our 6-year study corroborates the low neurosurgical rate reported in the literature for mTBI with small ICH. Nontransfer protocols may lead to a more efficient use of hospital resources while providing safe, effective and economical health care.

Should the management of isolated traumatic subarachnoid hemorrhage differ from concussion in the setting of mild traumatic brain injury

BACKGROUND In the setting of mild traumatic brain injury (TBI), the clinical significance of a traumatic subarachnoid hemorrhage (tSAH) has not been sufficiently studied. We examined the impact of an isolated tSAH on patient outcomes in the mild TBI population. METHODS We retrospectively identified all mild TBI patients (Glasgow Coma Scale score ≥13) who presented to a Level I trauma center over a 10-year period. We compared isolated tSAH patients with isolated concussion patients. χ(2) and logistic regression analyses were used to compare intensive care unit (ICU) admission, ICU length of stay (LOS), hospital LOS, progression of tSAH, in-hospital mortality, and disposition to rehabilitation. RESULTS There were 1,144 concussion and 117 tSAH patients included in our study. After adjustment, tSAH patients had increased odds of admission to the ICU (odds ratio, [OR] = 8.87; p < 0.0001), yet their ICU LOS was significantly shorter (OR = 0.29; p = 0.01). The overall hospital LOS and mortality rate were not significantly different between the TBI groups. When stratified by age, only the 40-year to 69-year-old tSAH patients had significantly increased adjusted odds of disposition to rehabilitation compared with concussion patients, independent of ICU admission (OR = 7.96; p = 0.004). None of the patients required any neurosurgical interventions. CONCLUSIONS We encourage healthcare facilities to consider revising or creating ICU admission criteria for the mild TBI population to help optimize the utilization of their ICUs. We believe clinicians should place more emphasis on variables such as age, comorbidities, and neurologic condition rather than the presence of a small volume of blood in the subarachnoid space when admitting mild isolated TBI patients to the ICU.

Association Between a Geriatric Trauma Resuscitation Protocol Using Venous Lactate Measurements and Early Trauma Surgeon Involvement and Mortality Risk

To investigate whether implementing a geriatric resuscitation protocol that uses lactate‐guided therapy with early trauma surgeon involvement is associated with lower mortality through the early recognition of occult hypoperfusion (OH).

The epidemiology of do-not-resuscitate orders in patients with trauma: a community level one trauma center observational experience

BackgroundDo-Not-Resuscitate (DNR) orders in patients with traumatic injury are insufficiently described. The objective is to describe the epidemiology and outcomes of DNR orders in trauma patients.MethodsWe included all adults with trauma to a community Level I Trauma Center over 6 years (2008–2013). We used chi-square, Wilcoxon rank-sum, and multivariate stepwise logistic regression tests to characterize DNR (established in-house vs. pre-existing), describe predictors of establishing an in-house DNR, timing of an in-house DNR (early [within 1 day] vs late), and outcomes (death, ICU stay, major complications).ResultsIncluded were 10,053 patients with trauma, of which 1523 had a DNR order in place (15%); 715 (7%) had a pre-existing DNR and 808 (8%) had a DNR established in-house. Increases were observed over time in both the proportions of patients with DNRs established in-house (p = 0.008) and age ≥65 (p < 0.001). Over 90% of patients with an in-house DNR were ≥65 years. The following covariates were independently associated with establishing a DNR in-house: age ≥65, severe neurologic deficit (GCS 3–8), fall mechanism of injury, ED tachycardia, female gender, and comorbidities (p < 0.05 for all). Age ≥65, female gender, non-surgical service admission and transfers-in were associated with a DNR established early (p < 0.05 for all). As expected, mortality was greater in patients with DNR than those without (22% vs. 1%), as was the development of a major complication (8% vs. 5%), while ICU admission was similar (19% vs. 17%). Poor outcomes were greatest in patients with DNR orders executed later in the hospital stay.ConclusionsOur analysis of a broad cohort of patients with traumatic injury establishes the relationship between DNR and patient characteristics and outcomes. At 15%, DNR orders are prevalent in our general trauma population, particularly in patients ≥65 years, and are placed early after arrival. Established prognostic factors, including age and physiologic severity, were determinants for in-house DNR orders. These data may improve physician predictions of outcomes with DNR and help inform patient preferences, particularly in an environment with increasing use of DNR and increasing age of patients with trauma.

Unintentional discontinuation of statins may increase mortality after traumatic brain injury in elderly patients: a preliminary observation.

Background The abrupt discontinuation of statin therapy has been suggested as being deleterious to patient outcomes. Although pre-injury statin (PIS) therapy has been shown to have a protective effect in elderly trauma patients, no study has examined how this population is affected by its abrupt discontinuation. This study examined the effects of in-hospital statin discontinuation on patient outcomes in elderly traumatic brain injury (TBI) patients. Methods This was a multicenter, retrospective cohort study on consecutively admitted elderly (≥ 55) PIS patients who were diagnosed with a blunt TBI and who had a hospital length of stay (LOS) ≥ 3 days. Patients who received an in-hospital statin within 48 hours of admission were considered continued, and patients who never received an in-hospital statin were considered discontinued. Differences in in-hospital mortality, having at least one complication, and LOS > 1 week were examined between those who continued and discontinued PIS. Results Of 93 PIS patients, 46 continued and 15 discontinued statin therapy. The two groups were equivalent vis-a-vis demographic and clinical characteristics. Those who discontinued statin therapy had a 4-fold higher mortality rate than those who continued (n = 4, 27% vs. n = 3, 7%, P = 0.055). Statin discontinuation did not have a higher complication rate, compared to statin continuation (n = 3, 20% vs. n = 7, 15%, P = 0.70), and no difference was seen in the proportion with a hospital LOS > 1 week (P > 0.99). Conclusions Though our study is not definitive, it does suggest that the abrupt, unintended discontinuation of statin therapy is associated with increased mortality in the elderly TBI population. Continuing in-hospital statin therapy in PIS users may be an important factor in the prevention of in-hospital mortality in this elderly TBI population.

A standardized neurointerventional thrombectomy protocol leads to faster recanalization times

Background and purpose Intra-arterial therapy (IAT) is most effective when performed rapidly after ischemic stroke onset. However, there are limited performance benchmarks in IAT and there is a scarcity of information on how to structure an effective IAT protocol and its impact on time to treatment. The objective of our study was to detail a standardized IAT protocol, and to assess its influence on time to treatment in ischemic stroke. Methods This was a retrospective observational study over 4 years at a comprehensive stroke center. A standardized IAT protocol was implemented in June 2013 that included pre-notifying the stroke team before hospital arrival, defining clinician roles, processing tasks in parallel, and standardizing IAT procedures. Three time metrics were examined and reported as median (IQR) minutes: arrival to CT imaging, CT to groin puncture, and puncture to recanalization. We compared these metrics in patients admitted before implementation (January 2012–May 2013) to patients admitted after (June 2013–December 2015) using Wilcoxon Mann–Whitney tests. Results 380 patients were included. After the protocol was implemented, there were significant reductions in time from arrival to CT (17 (14–21) vs 13 (11–19) min, p<0.001), CT to puncture (46 (30–82) vs 31 (23–54) min, p<0.001), and puncture to recanalization (65 (33–90) vs 37 (22–65) min, p<0.001). 60% of time was saved during puncture to recanalization. Significant reductions in time were observed during both normal working hours and off-hours. Conclusions Implementation of a standardized protocol resulted in a significant reduction in time to recanalization for patients with an ischemic stroke. A standardized IAT protocol decreases time to recanalization when team roles are clearly defined, tasks are processed in parallel, and procedures are standardized.

A rapid, real-time quantitative polymerase chain reaction test for the identification of pathogens in bronchoalveolar lavage samples.

BACKGROUND Standard bacteriologic culture techniques offer results within 2 days to 3 days, precluding a focused and timely antibiotic therapy in ventilated trauma patients. Our laboratory developed a real-time quantitative polymerase chain reaction (qPCR) test that can detect 25 different bacteria and fungi and methicillin resistance and offers results within 3 hours. The objective of this study was to compare the qPCR method to standard culture techniques. METHODS This was a prospective observational cohort study at a Level I trauma center from 2009 to 2012. Adult trauma patients on ventilation, receiving at least one bronchoalveolar lavage (BAL) with culture results were eligible for inclusion. DNA was isolated from the BAL samples and analyzed in 96-well plates using qPCR. Student’s t tests were used to examine differences in mean qPCR cycle counts. Sensitivities, specificities, negative predictive values, and positive predictive values were calculated for the qPCR primer sets. RESULTS There were 28 BALs in the study. The qPCR method detected a total of 165 organisms, and culture methods found 54. The qPCR test had an overall sensitivity of 85%, specificity of 74%, negative predictive value of 98%, and positive predictive value of 27%. Those organisms that were only identified through qPCR had significantly less DNA than those identified through both qPCR and quantitative culture (28.8 vs. 23.3, p < 0.001). Concurrent antibiotic therapy was found to decrease the qPCR specificity in some primer sets, and methicillin resistance was only found in BAL samples that were concurrent with antibiotics. CONCLUSION The qPCR method shows promising initial diagnostic value. Many of the organisms not identified by quantitative culture had late cycle calls, suggesting that they might have been in quantities too low to result in culture identification. Once refined, our qPCR method has the potential to identify pathogens faster and earlier than standard quantitative culture methods, allowing for targeted antibiotic therapy within 3 hours. LEVEL OF EVIDENCE Diagnostic test, level II

A 5-year review of a trauma-trained hospitalist program for trauma patients: A matched cohort study.

BACKGROUND Level I trauma centers have requirements on the percentage of trauma patients admitted to either a trauma surgeon or surgical subspecialist; however, surgical resources are in steady decline. Therefore, a trauma system might better utilize its surgical resources if trained hospitalists admitted a larger percentage of mild to moderately injured trauma patients. The objective of this report is to provide a 5-year evaluation of a trauma medical service (TMED) at treating mild to moderately injured trauma patients. METHODS Adult trauma patients consecutively admitted to a Level I trauma center between January 2006 and December 2010 were analyzed. Patients admitted to trauma surgical services were matched 1:1 to those admitted to TMED, via propensity scores. Paired t tests examined differences in hospital duration of stay (DOS), and exact conditional logistic regression examined differences in the odds of having a delayed diagnosis, developing a complication, and dying. RESULTS Of 1,202 TMED patients, 494 were matched; matched TMED patients had similar patient outcomes to nonmatched TMED patients. There were no differences between study groups in the mean hospital DOS, the proportion having a delayed diagnosis, or in the odds of dying in the hospital (P > .05 for all). The TMED group had a nominally higher complication rate (P = .12) owing to a higher rate of urinary tract infections. CONCLUSION Since its inception, the TMED service has successfully and safely treated mild to moderately injured trauma patients, and decreased the dependency on trauma surgical services. Trauma centers might utilize declining surgical services more efficiently with the addition of trauma medical hospitalists.

A Four-Year Experience of Symptomatic Intracranial Hemorrhage Following Intravenous Tissue Plasminogen Activator at a Comprehensive Stroke Center

BACKGROUND To describe the 4-year experience of symptomatic intracranial hemorrhage (sICH) rate at a high-volume comprehensive stroke center. METHODS All admitted adult (≥18 years) patients presenting with an ischemic stroke from 2010 to 2013 were included in this study. The primary outcome was sICH, defined as any hemorrhage with neurological deterioration (change in National Institutes of Health Stroke Scale score ≥4) within 36 hours of intravenous tissue plasminogen activator (IV-tPA) treatment, or any hemorrhage resulting in death. Secondary outcomes were in-hospital mortality and having a favorable modified Rankin Scale (mRS) score (≤2). RESULTS A total of 1925 did not receive intravascular (IV) or intra-arterial (IA) therapy; only 451 received IV therapy; and 175 received both IV and IA therapies. In IV-only patients, the overall rate of sICH was 2.2%; in IV and IA patients, the rate was 5.7%; and in patients who received no therapy, the rate was .4%. The IV-only group had an sICH rate of .9% in 2013. There were no differences in the adjusted odds of dying in the hospital between the study groups. IV-only treatment offered significantly better odds of achieving a favorable functional outcome, compared to no therapy, among patients with moderate stroke severity, whereas IV and IA treatments offered significantly better odds among patients with severe strokes. The odds of achieving a favorable functional outcome by discharge were decreased by 97% if patients suffered an sICH (OR = .03, 95%CI = .004, .19). CONCLUSIONS Despite an increased risk of sICH with IV-tPA, treatment with IV-tPA continues to be associated with increased odds of a favorable discharge mRS.