The Standardization of Outpatient Procedure (STOP) Narcotics after anorectal surgery: a prospective non-inferiority study to reduce opioid use.

BACKGROUND: Prescription of opioid medication after ambulatory anorectal surgery may be excessive and lead to opioid misuse. The purpose of this study was to evaluate the efficacy of a multi-modality opioid-sparing approach to control postoperative pain and reduce opioid prescriptions after outpatient anorectal surgery. METHODS: A prospective non-inferiority pre- and post-intervention study was completed at three academic hospitals. Patients included were 18-75 years of age who had outpatient anorectal surgeries. The Standardization of Outpatient Procedure (STOP) Narcotics intervention was implemented, which is a multi-pronged analgesia bundle integrating patient education, health care provider education, and intra-/postoperative analgesia focused on multi-modal pain control strategies and opioid-reduced prescriptions. The primary outcome was patient-reported average pain in the first 7 postoperative days. Secondary outcomes included patient-reported quality of pain management, medication utilization, prescription refills and medication disposal. RESULTS: Ninety-three patients had outpatient anorectal surgery (42 pre-intervention and 51 post-intervention). No difference was seen in average postoperative pain in the pre- vs. post-intervention groups (2.8 vs. 2.6 on an 11-point scale, p = 0.33) or patient-reported quality of pain control (good/very good in 57% vs. 63%, p = 0.58). The median oral morphine equivalents (OME) prescribed was significantly less [112.5 (IQR 50-150) pre-intervention vs. 50 (IQR 50-50) post-intervention, p < 0.001]. In the post-intervention group, only 45% of patients filled their opioid prescription and median opioid use was 12.5 OME (2.5 pills). CONCLUSIONS: While pain control after anorectal surgery must consider the individual patient's needs, a standardized pain care bundle significantly decreased opioid prescribing without an increase in patient-reported postoperative pain.

TAK-228 (formerly MLN0128), an investigational dual TORC1/2 inhibitor plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies.

PURPOSE: This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. METHODS: Sixty-seven patients received TAK-228 6-40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m2 (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20). Doses were escalated using a modified 3 + 3 design, based upon dose-limiting toxicities in cycle 1. RESULTS: TAK-228 pharmacokinetics exhibited dose-dependent increase in exposure when dosed with paclitaxel and no apparent differences when administered with or 24 h after paclitaxel. Dose-limiting toxicities were dehydration, diarrhea, stomatitis, fatigue, rash, thrombocytopenia, neutropenia, leukopenia, and nausea. The maximum tolerated dose of TAK-228 was determined as 10-mg QDx3d QW; the expansion phase proceeded with 8-mg QDx3d QW. Overall, the most common grade ≥3 drug-related toxicities were neutropenia (21%), diarrhea (12%), and hyperglycemia (12%). Of 54 response-evaluable patients, eight achieved partial response and six had stable disease lasting ≥6 months. CONCLUSION: TAK-228 demonstrated a safety profile consistent with other TORC inhibitors and promising preliminary antitumor activity in a range of tumor types; no meaningful difference was noted in the pharmacokinetics of TAK-228 when administered with or 24 h after paclitaxel. These findings support further investigation of TAK-228 in combination with other agents including paclitaxel, with/without trastuzumab, in patients with advanced solid tumors. CLINICALTRIALS. GOV IDENTIFIER: NCT01351350.

Are retrievable vena cava filters placed in trauma patients really retrievable?

PURPOSE: Concerns have arisen regarding the use of retrievable inferior vena cava filters (rIVCFs) in trauma patients due to increasing reports of low retrieval rates. We hypothesized that complete follow-up with a dedicated trauma nurse practitioner would be associated with a higher rate of retrievability. This study was undertaken to determine the rate of retrievability of rIVCFs placed in a Canadian Lead Trauma Centre, and to compare the rate of retrievability in our trauma population to our non-trauma patients. METHODS: We performed a retrospective cohort study of all patients with rIVCF placed between Jan 1 2000 and June 30 2014. Data were collected on demographics, indication for filter placement, retrieval status, and reasons for non-retrieval. Comparison was made between trauma patients and non-trauma patients. RESULTS: A total of 374 rIVCFs were placed (61 in trauma patients and 313 in non-trauma patients) and follow-up was complete for the entire cohort. Filter retrieval was achieved in 86.9 % of trauma patients. Reasons for non-retrieval were technical in two patients, and death before retrieval in six patients. Retrieval was successful in 48.9 % of non-trauma patients. CONCLUSIONS: This study demonstrates that rIVCFs can be successfully retrieved amongst trauma patients. We demonstrated a higher rate of successful retrieval amongst trauma patients than non-trauma patients in our institution. Careful patient follow-up may play a role in successful retrieval of rIVCFs.

Surgical management for rectal prolapse: an update.

Surgical management of rectal prolapse remains a challenge with the bredth of choices available and varies on the international, national, regional and locoregional level depending on expertise, comfort and perception of the available evidence. Long-standing opinions on approach of repair, abdominal vs. perineal, have been based on limited evidence and on anesethetic methods that are now relics of the past. Laparoscopic surgical repair and modern anesthethesia has made the abdominal approach more attractive even to the octagenerian with multiple comorbidities. Surgical management should still be individualized and prior to offering surgical correction of rectal prolapse one must understand each patient's syptoms, particularly incontinence and constipation, as well the effect rectal prolapse has on the patient's overall quality of life.

A cohort study to identify simple clinical tests for chronic respiratory failure in obese patients with sleep-disordered breathing.

BACKGROUND: Chronic respiratory failure complicating sleep-disordered breathing in obese patients has important adverse clinical implications in terms of morbidity, mortality and healthcare utilisation. Screening strategies are essential to identify obese patients with chronic respiratory failure. METHOD: Prospective data were collected from patients with obesity-related sleep-disordered breathing admitted for respiratory assessment at a UK national sleep and ventilation centre. Hypercapnia was defined as an arterial partial pressure of carbon dioxide of >6kPa. RESULTS: 245 obese patients (56±13 years) with a body mass index of 48±12 kg/m(2), forced vital capacity (FVC) of 2.1±1.1 L, daytime oximetry (SpO2) of 91±6% and abnormal overnight oximetry were included in the analysis. Receiver operator curve analysis for the whole group showed that an FVC ≤3 L had a sensitivity of 90% and a specificity of 41% in predicting hypercapnia, and an SpO2 ≤95% had a sensitivity of 83% and a specificity of 63% in predicting hypercapnia. Gender differences were observed and receiver operator curve analysis demonstrated 'cut-offs' for (1) SpO2 of ≤95% for men and ≤93% for women and (2) FVC of ≤3.5 L for men and ≤2.3 L for women, in predicting hypercapnia. CONCLUSIONS: The measurement of FVC and clinic SpO2 in obese patients with abnormal overnight limited respiratory studies predicted hypercapnia. This may have clinical utility in stratifying patients attending sleep clinics.

Development and psychometric evaluation of the Environment-Behavior Interaction Code (EBIC).

BACKGROUND: Although the behavioral changes with progressive dementia are seen to increasingly depend on the environmental context until late stage disease, measurement has not reflected this interaction in real time to allow examination of antecedents to disruptive behavior. OBJECTIVES: To develop and evaluate the psychometric properties of the Environment-Behavior Interaction Code (EBIC) for use in dementia care research with either sequential or nonsequential analyses of behavioral data. METHOD: Development of the computer-based (sequential event format) EBIC provided an observational coding system to classify all behavior and environmental context in real time, so that the probability of social environmental antecedents to resident disruptive behavior could be estimated. A checklist (interval format) EBIC, based on the same behavioral taxonomy, was developed for clinical outcome research. A total of 158 elderly residents of dementia care units were purposively selected from three large long-term care facilities for the psychometric study components. RESULTS: Psychometric results indicated significant (p < 0.01) known-groups validity for the disruptive behavior construct, which was defined as a composite of aversive, harmful, and high intensity neutral behavior. Interrater agreement for the event format of the EBIC was estimated by average kappa (0.65) and percentage agreement (78%). For the interval format, the mean interrater kappa was 0.80 with 96% agreement. Stability of the event format using a 2-week retest interval ranged from r= .50 (positive behavior) to r = 0.73 (negative behavior, defined as aversive + harmful). On replication with a new sample, stability was higher for positive (r = 0.92) and negative (r = 0.95) components, and for composite scores of nondisruptive (positive + low intensity neutral; r = 0.65) and disruptive (r= 0.85) behavior. CONCLUSION: This research provided support for the reliability and validity of both event and interval EBIC formats. Measurement using the EBIC taxonomy has applicability to dementia care research questions that call for either sequential analysis of social interactions or nonsequential analysis of behavioral outcomes in intervention studies.

High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer.

BACKGROUND: The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. METHODS: Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. RESULTS: Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths. CONCLUSIONS: This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

A phase II trial of cisplatin and prolonged administration of oral etoposide in extensive-stage small cell lung cancer.

Etoposide is a schedule-dependent agent with greater activity against small cell lung cancer (SCLC) when a given dose is administered over several days compared with a 1-day administration of the same dose. In an attempt to capitalize on the schedule dependency of etoposide, 22 previously untreated extensive-stage SCLC patients were given cisplatin (100 mg/m2 on day 1) plus 21 days of low-dose, oral etoposide (50 mg/m2/d). Chemotherapy was repeated every 28 days for four cycles. Complete blood counts were monitored weekly, and etoposide was discontinued if either the leukocyte or platelet count dropped below 2000/microliters or 75,000/microliters, respectively. All 22 patients were evaluable for response; 18 had either a complete (9%) or partial response (73%), an overall response rate of 82% (95% confidence interval, 62% to 93%). The median response duration was 7 months, and the median survival was 9.9 months (range, 1 to 17+ months). Sixteen (73%) patients received all planned cycles of etoposide. In Cycle 1 of chemotherapy, the median leukocyte nadir was 2700/microliters (range, 100 to 6300/microliters), and median platelet nadir was 180,000/microliters (range, 51,000 to 397,000/microliters). Life-threatening leukopenia (less than 1000/microliters) was rare (3 of 74 cycles). There were three treatment-related deaths, only one of which was associated with neutropenia. One patient had mild renal insufficiency that resolved after discontinuation of therapy. Alopecia was observed in all patients, but other nonhematologic toxicities were uncommon. A randomized study is necessary to determine if this schedule of cisplatin and etoposide administration is superior to more standard methods. However, these data do not indicate a major survival benefit will be derived from increasing the duration of etoposide administration when used in combination with cisplatin given every 28 days.

Prolonged administration of oral etoposide plus cisplatin in extensive stage small cell lung cancer.

Etoposide is a highly schedule-dependent agent. We previously reported that a 21-day schedule of oral etoposide had good activity in small cell lung cancer (SCLC). The current phase II study was designed to test the combination of 21-day oral etoposide with cisplatin in hopes of capitalizing on etoposide's schedule dependency. Sixteen extensive stage SCLC patients were treated with cisplatin 100 mg/m2 day 1 plus 21 days of low-dose oral etoposide 50 mg/m2/day. Chemotherapy was repeated every 28 days for 4 cycles. Blood counts were monitored weekly, and etoposide was discontinued if the leukocyte or platelet count dropped below 2.0 x 10(9)/l or 75 x 10(9)/l, respectively. Fifteen of 16 patients were evaluable for response; 13 achieved either a complete (13%) or partial response (73%), for an overall response rate of 86% (95% confidence interval, 62-93%). Median response duration was approximately 7 months; median survival was not reached. Thirteen patients (81%) received all the planned cycles of chemotherapy. In cycle 1 of chemotherapy, the median leukocyte nadir was 2.8 x 10(9)/l (range, 0.1-6.3 x 10(9)/l; median platelet nadir was 180 x 10(9)/l (range, 51-397 x 10(9)/l). Life-threatening leukopenia (less than 1.0 x 10(9)/l) was unusual (2 of 58 cycles). There was 1 treatment-related death. One patient developed mild renal insufficiency that resolved after therapy. Nonhematologic toxicities were uncommon, but alopecia occurred in all patients. These data do not suggest that a major survival benefit will be derived for patients with extensive stage SCLC by increasing the duration of etoposide administration when used in combination with cisplatin. A randomized study is needed to determine if this long-term schedule of etoposide plus cisplatin is superior to the standard schedule of etoposide plus cisplatin.

Normal and malignant human myeloid progenitors differ in their sensitivity to hyperthermia.

The effect of in vitro hyperthermia on normal human bone marrow granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was compared to its effect on clonogenic acute nonlymphocytic leukemic (ANLL) cells. Mononuclear normal bone marrow cells, blasts from patients with ANLL, and HL-60 cells were incubated at room temperature (control) and at 42 degrees-44 degrees C for 0-120 min prior to assay in methylcellulose. The heat sensitivity of the leukemic cells was significantly greater than that of normal bone marrow progenitors. Two-h exposure to 43 degrees C, for example, resulted in survival of 52% of normal marrow CFU-GM, whereas only 3% of leukemic CFU-GM survived (p less than 0.001 for HL-60 cells and p less than 0.005 for patient blast cells). To determine the effect of hyperthermia on more primitive progenitors and on marrow stromal cells, long-term cultures of normal bone marrow were established using control and heat-treated cells. Generation of CFU-GM was detected in the nonadherent fraction of hyperthermia-treated samples throughout the 5-week culture period. Although stromal development was slightly delayed, hyperthermia-treated cells were able to establish stromal layers similar to control cells. These results indicate that normal bone marrow committed progenitor cells are more resistant to hyperthermia than are myeloid leukemic cells. Normal stromal cells and primitive cells assayed in long-term culture are also resistant to hyperthermia that is toxic for leukemic cells. Because of this differential sensitivity to heat, ex vivo hyperthermia may be applicable for removing residual leukemic cells from bone marrow harvested for autologous transplantation.