Low Non-structured Antiretroviral Therapy Interruptions in HIV-Infected Persons Who Inject Drugs Receiving Multidisciplinary Comprehensive HIV Care at an Outpatient Drug Abuse Treatment Center.

Continuous HIV treatment is necessary to ensure successful combined antiretroviral therapy (cART). The aim of this study was to evaluate the incidence of patient-initiated non-structured treatment interruptions in HIV-infected persons who inject drugs and who received a multidisciplinary comprehensive program, including medical HIV care, drug-dependence treatment and psychosocial support, at a drug outpatient addiction center. Non-structured treatment interruptions were defined as ≥30 consecutive days off cART without medical indication. During a median follow-up of 53.8 months, 37/132 (28 %) patients experienced the first non-structured treatment interruptions. The cumulative probability of cART interruption at 5 years was 31.2 % (95 % CI 22.4-40.0). Current drug use injection ≥1/day (HR 14.77; 95 % CI 5.90-36.96) and cART naive patients (HR 0.35, 95 % CI 0.14-0.93) were predictive factors for non-structured treatment interruptions. HIV care provided at a drug addiction center is a useful strategy to sustain continuous cART, however, drug abstinence is essential for the long-term maintenance of cART.

Three measures of physical rehabilitation effectiveness in elderly patients: a prospective, longitudinal, comparative analysis.

BACKGROUND: Rehabilitation success is measured by instruments that assess performance of activities of daily living. Guidelines on the use and choice of these instruments are lacking. The present study aimed to analyse prognostic indicators of physical rehabilitation effectiveness in elderly patients according to three rehabilitation impact indices. METHODS: Prospective, longitudinal study in a post-acute care unit. The study included rehabilitation-eligible deconditioned elderly in-patients prospectively admitted to post-acute care (n = 685, aged 83.2 ± 8.3 years, mean length of stay 15 ± 9.2 days). DATA COLLECTION: Premorbid health status variables (PHSV): age, sex, comorbidity (Charlson index), medical history (heart failure, pulmonary disease, cerebrovascular disease, dementia), previous living situation and pre-admission functional status (premorbid Lawton and Barthel indices). Admission health status variables (AHSV): main diagnoses, referral source, physical (Barthel-adm) and cognitive function (Pfeiffer test), undernutrition and dysphagia. OUTCOME MEASURES: Absolute functional gain (AFG, admission-to-discharge Barthel change), relative functional gain (RFG, achieved percentage of potential gain) and rehabilitation efficiency index (REI, AFG over length of stay). Univariate analysis considered these parameters, along with PHSV and AHSV. Multivariate logistic regression analysis was performed for AFG ≥20, RFG ≥35 % and REI ≥ 0.50. RESULTS: Greater AFG was associated with 14 variables, 8 PHSV (57.1 %) and 6 AHSV (42.8 %); greater RFG with 9 variables, 3 PHSV (33.3 %) and 6 AHSV (66.6 %); and REI with 9 variables, 4 PHSV (44.4 %) and 5 AHSV (55.5 %). Mean AFG value was 34.5 ± 15.8 in patients who achieved complete recovery (RFG 100 %, n = 189, 27.5 %) and 35.3 ± 15.0 (p = 0.593) in the remaining patients (n = 311, 45.4 %). In multivariate analysis, only Barthel-adm was related to all three rehabilitation impact indices. CONCLUSIONS: Both premorbid and acute-process variables have a greater impact on AFG and REI, compared to RFG. Although AFG gives information about the degree of reduction in dependence, it does not provide clinical information about post-rehabilitation functional status (mean AFG values did not differ between patients with and without complete recovery). A future implication for evaluating rehabilitation effectiveness in elderly patients is to recommend RFG corrected by premorbid Barthel score, which is less affected by previous health conditions, as the optimum method to assess the degree to which maximum potential improvement was achieved.

Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy.

BACKGROUND: Concern regarding the QTc interval in human immunodeficiency virus (HIV)-infected patients has been growing in recent years, and cases of prolonged QTc interval and torsades de pointes have been described in HIV-infected patients on methadone therapy. This study aimed to determine the prevalence and factors associated with long QTc interval in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. METHODS: A cross-sectional study was conducted in opioid-dependent HIV-infected patients on methadone maintenance therapy at a drug abuse outpatient center. Patients with any cardiac disease, drug-positive urine test, electrolyte abnormalities, and changes in their antiretroviral therapy (ART) or methadone doses in the last 2 months were excluded. Heart rate and QT interval in lead II were measured using the Bazett formula. RESULTS: Ninety-one patients were included: 58 (63.7%) were men with a median age of 44.5 years and 68 of 91 (74.7%) were on ART. Median methadone dose was 70 mg/day (range 15-250 mg/day) and mean QTc interval was 438 ± 34 ms. Prolonged QTc interval (>450 ms) was documented in 33 of 91(36.3%) patients, and 3 of 91 (3.2%) had QTc >500 ms. On multiple linear regression analysis, methadone doses (P = .005), chronic hepatitis C-induced cirrhosis (P = .008), and being ART-naive (P = .036) were predictive of prolonged QTc. CONCLUSIONS: The prevalence of prolonged QTc interval in opioid-dependent HIV-infected patients on methadone maintenance therapy is high. Risk factors for prolongation of the QTc interval are chronic hepatitis C-induced cirrhosis, higher methadone doses, and being ART-naive. Thus, electrocardiographic monitoring is required to minimize cardiovascular morbidity and mortality in this specific HIV group.

mTOR signaling pathway in penile squamous cell carcinoma: pmTOR and peIF4E over expression correlate with aggressive tumor behavior.

PURPOSE: Penile squamous cell carcinoma is a rare neoplasm associated with a high risk of metastasis and morbidity. There are limited data on the role of the mTOR signaling pathway in penile squamous cell carcinoma carcinogenesis and tumor maintenance. We assessed a possible role for mTOR signaling pathway activation as a potential predictive biomarker of outcome and a therapeutic target for penile cancer. MATERIAL AND METHODS: A cohort of 67 patients diagnosed with invasive penile squamous cell carcinoma from 1987 to 2010 who had known HPV status were selected for study. Tissue microarrays were constructed with 67 primary penile squamous cell carcinomas, matched normal tissues and 8 lymph node metastases. Immunohistochemical staining was performed for p53, pmTOR, pERK, p4E-BP1, eIF4E and peIF4E. Expression was evaluated using a semiquantitative H-score on a scale of 0 to 300. RESULTS: Expression of pmTOR, p4E-BP1, eIF4E and peIF4E was increased in penile tumors compared with matched adjacent normal tissues, indicating activation of the mTOR signaling pathway in penile tumorigenesis. Over expression of pmTOR, peIF4E and p53 was significantly associated with lymph node disease. peIF4E and p53 also correlated with a poor outcome, including recurrence, metastasis or disease specific death. In contrast, pERK and p4E-BP1 were associated with lower pT stages. pmTOR and intense p53 expression was associated with HPV negative tumors. CONCLUSIONS: Activation of mTOR signaling may contribute to penile squamous cell carcinoma progression and aggressive behavior. Targeting mTOR or its downstream signaling targets, such as peIF4E, may be a valid therapeutic strategy.

Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: correlation with pathologic subtypes, p16(INK4a) expression, and prognosis.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a tumor with a high metastatic potential. In PSCC the attributable fraction to human papillomavirus (HPV) is not well established. OBJECTIVE: We sought to provide novel data about the prevalence of HPV in a large series of penile intraepithelial neoplasia (PeIN) and invasive PSCC, correlating the results with the histologic subtype, p16(INK4a) immunostaining, and prognosis. METHODS: A total of 82 PSCC were included in the study, 69 invasive and 13 PeIN. HPV detection was performed by polymerase chain reaction with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe assay. P16(INK4a) immunohistochemical expression on tissue microarrays was also analyzed. RESULTS: HPV DNA was identified in 31 of 77 (40.2%) PSCC (22 of 67 invasive and 9 of 10 PeIN). In 25 of 31 (80.6%) cases HPV-16 was identified. HPV detection was significantly associated with some histologic subtypes: most basaloid and warty tumors were high-risk HPV (hrHPV) positive, whereas only 15% of usual PSCC were hr-HPV positive. All hrHPV-positive PSCC had an adjacent undifferentiated PeIN. Strong p16(INK4a) immunostaining correlated with hrHPV infection. Most undifferentiated PeIN showed p16(INK4a) immunohistochemical overexpression. Both hrHPV-positive and p16(INK4a)-positive tumors showed a better overall survival without reaching statistical significance. LIMITATIONS: This was a retrospective study. CONCLUSIONS: Our results suggest that most hrHPV-positive PSCC develop from undifferentiated hrHPV-positive PeIN. P16(INK4a) immunostaining may be useful in identifying both etiologically related hrHPV-positive tumors and those with better outcome. The routine use of p16(INK4a) staining should be incorporated in histologic evaluation of PSCC.

Antiretroviral Therapy (ART) Use, Human Immunodeficiency Virus (HIV)-1 RNA Suppression, and Medical Causes of Hospitalization Among HIV-Infected Intravenous Drug Users in the Late ART Era.

BACKGROUND: Antiretroviral therapy (ART) has reduced the rates and changed the causes of hospital admission. However, human immunodeficiency virus-positive intravenous drug users (HIV-IDU) continue to have increased hospitalizations and discharge diagnosis are less defined in the late ART era. Our aim was to examine ART use, HIV-1 RNA suppression, and hospital discharge diagnoses among HIV-IDU admitted to an urban hospital. METHODS: A retrospective analysis was made of HIV-IDU admitted for medical causes for the first time (2006-2010). Surgical, obstetric, or mental (except HIV-associated neurocognitive disorder) diagnoses were excluded. Clinical characteristics, number of admissions, and primary discharge diagnoses were determined for each patient. RESULTS: Three hundred and seventy-five admissions were recorded among 197 hospitalized HIV-IDU. Lifetime prevalence of ART use was 83.2% (164 of 197) and the rate of HIV-1 RNA <50 copies/mL was 38.1% (75 of 197). Primary discharge diagnosis groups were as follows: bacterial infections (59.2%), chronic end-organ damage (16.8%), complications derived from injected drug use (16.8%), malignancies (9.1%), and opportunistic infections (6.6%). Chronic end-organ damage was diagnosed more frequently in patients with HIV-1 RNA <50 copies/mL (36% vs 4.9%; P < .000), and complications derived from injected drug use (23.8% vs 5.3%; P < .0008) and acquired immune deficiency syndrome (AIDS) opportunistic infections (19.8% vs 1.3% P < .019) were usually diagnosed in patients with HIV-1 RNA detectable viral load. CONCLUSIONS: Human immunodeficiency virus-positive intravenous drug users are admitted to hospitals mainly for non-AIDS-related illnesses; however, sustained HIV-1 RNA viral load suppression is poor and determines hospital discharge diagnoses. Providers need to be aware of the management of HIV-related comorbidities and reinforce strategies to improve ART retention in this population.

Morbidity and mortality in a large series of surgical patients with pulmonary metastases of colorectal carcinoma: a prospective multicentre Spanish study (GECMP-CCR-SEPAR).

OBJECTIVE: Little information is available on postoperative morbidity and mortality after pulmonary metastasectomy. We describe the postoperative morbidity and mortality in a large multicentre series of patients after a first surgical procedure for pulmonary metastases of colorectal carcinoma (CRC) and identify the pre- and intraoperative variables influencing the clinical outcome. METHODS: A prospective, observational and multicentre study was conducted. Data were collected from March 2008 to February 2010. Patients were grouped into Groups A and B according to the presence or absence of postoperative complications. Variables in both groups were compared by univariate and multivariate analyses. P-values of <0.05 were considered statistically significant. RESULTS: A total of 532 patients (64.5% males) from 32 hospitals were included. The mean (SD) ages of both study groups were similar [68 (10) vs 67 (10) years, P = NS). A total of 1050 lung resections were performed (90% segmentectomies or wedge, n = 946 and 10% lobectomies or greater, n = 104). Group A included 83 (15.6%) patients who developed a total of 100 complications. These included persistent air leaks in 18, atelectasis in 13, pneumonia in 13, paralytic ileum in 12, arrhythmia in 9, acute respiratory distress syndrome in 4 and miscellanea in 31. Reoperation was performed in 5 (0.9%) patients due to persistent air leaks in 4 and lung ischaemia in 1. The mortality rate was 0.4% (n = 2). Causes of death were sepsis in 1 patient and ventricular fibrillation in 1. In the multivariate analysis, lobectomy or greater lung resection [odds ration (OR) 1.9, 95% confidence interval (95% CI) 1.04-3.3, P = 0.03], respiratory co-morbidity (OR 2.3, 95% CI 1.1-4.6, P = 0.01) and cardiovascular co-morbidity (OR 2, 95% CI 1-3.8, P = 0.02) were independent risk factors for postoperative morbidity. Video-assisted surgery vs thoracotomy showed a protective effect (OR 0.3, 95% CI 0.1-0.8, P = 0.01). CONCLUSIONS: The first episode of lung surgery for pulmonary metastases of CRC was associated with very low mortality and reoperation rates (<1%). The postoperative morbidity rate was 16%. Independent risk factors of postoperative morbidity were major lung resection and respiratory and/or cardiovascular co-morbidity. Video-assisted surgery showed a protective effect.

Sarcopenia, physical rehabilitation and functional outcomes of patients in a subacute geriatric care unit.

Sarcopenia is the loss of muscle mass and strength, which in the elderly can result in disability and affect functional outcomes after hospitalization. The aim of this study was to evaluate the functional outcomes and mortality during hospitalization and at three months post-discharge, according to the presence of sarcopenia. Prospective study of 99 patients (38.4% men, aged 84.6) admitted in a subacute geriatric care unit who underwent a rehabilitation intervention. Main outcomes were mortality and functional improvement at discharge and at three-month follow-up. Sarcopenia was assessed by handgrip strength (hydraulic dynamometer) and by body composition bioimpedance. Forty-six (46.5%) patients met diagnostic criteria of sarcopenia. Patients with sarcopenia had a worse prior functional status than those without the condition (Barthel Index: 64.2±22.8 vs 73.3±21.8; p=0.04) but both groups had similar functional decline at admission (Barthel Index: 24±15.1 vs 28.5±15.2; p=0.1) and achieved similar functional improvement at discharge (20.4±18.3 vs 27.4±21; p=0.08). Barthel Index at discharge remained comparatively worse in patients with sarcopenia (44.2±26.6 vs 55.9±26.7; p=0.03). After completing a 3-month at-home rehabilitation program, no changes in functional capacity were observed in patients with sarcopenia; their peers improved their Barthel Index scores (45.5±24.8 vs 61.6±26.6; p=0.007). Mortality rates at 3-month follow-up did not differ between groups. In conclusion, patients with sarcopenia had a worse functional status, similar functional improvement during hospitalization and a lack of recovery after returning home. Further studies are needed to establish long-terms effects on mortality.