The Hospital-Acquired Conditions (HAC) reduction program: using cranberry treatment to reduce catheter-associated urinary tract infections and avoid Medicare payment reduction penalties.

OBJECTIVE: The Affordable Care Act (ACA) established the Hospital-Acquired Condition (HAC) Reduction Program. The Centers for Medicare and Medicaid Services (CMS) established a total HAC scoring methodology to rank hospitals based upon their HAC performance. Hospitals that rank in the lowest quartile based on their HAC score are subject to a 1% reduction in their total Medicare reimbursements. In FY 2017, 769 hospitals incurred payment reductions totaling $430 million. This study analyzes how improvements in the rate of catheter-associated urinary tract infections (CAUTI), based on the implementation of a cranberry-treatment regimen, impact hospitals' HAC scores and likelihood of avoiding the Medicare-reimbursement penalty. METHODS: A simulation model is developed and implemented using public data from the CMS' Hospital Compare website to determine how hospitals' unilateral and simultaneous adoption of cranberry to improve CAUTI outcomes can affect HAC scores and the likelihood of a hospital incurring the Medicare payment reduction, given results on cranberry effectiveness in preventing CAUTI based on scientific trials. The simulation framework can be adapted to consider other initiatives to improve hospitals' HAC scores. RESULTS: Nearly all simulated hospitals improved their overall HAC score by adopting cranberry as a CAUTI preventative, assuming mean effectiveness from scientific trials. Many hospitals with HAC scores in the lowest quartile of the HAC-score distribution and subject to Medicare reimbursement reductions can improve their scores sufficiently through adopting a cranberry-treatment regimen to avoid payment reduction. LIMITATIONS: The study was unable to replicate exactly the data used by CMS to establish HAC scores for FY 2018. The study assumes that hospitals subject to the Medicare payment reduction were not using cranberry as a prophylactic treatment for their catheterized patients, but is unable to confirm that this is true in all cases. The study also assumes that hospitalized catheter patients would be able to consume cranberry in either juice or capsule form, but this may not be true in 100% of cases. CONCLUSION: Most hospitals can improve their HAC scores and many can avoid Medicare reimbursement reductions if they are able to attain a percentage reduction in CAUTI comparable to that documented for cranberry-treatment regimes in the existing literature.

Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115.

We designed a trial using two sequential cycles of modified high-dose melphalan at 100 mg/m(2) and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM) patients through SWOG-0115. The primary objective was to evaluate OS. From 2004 to 2010, 93 eligible patients were enrolled at 17 centers in the United States (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and ALM was 68 months and 47 months, respectively, and has not been reached for patients with hM. The median PFS for patients with AL and ALM was 38 months and 16 months, respectively, and has not been reached for patients with hM. The treatment-related mortality (TRM) was 12% (11/93) and was observed only in patients with AL after SCT. Grade 3 and higher non-hematologic adverse events were experienced by 81%, 67% and 57% of patients with AL, ALM and hM, respectively, during the first and second HDM/SCT. This experience demonstrates that with careful selection of patients and use of mHDM for SCT in patients with AL, ALM and hM, even in the setting of a multicenter study, OS can be improved with acceptable TRM and morbidity.

Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols.

To determine whether primary plasma cell leukemia (PPCL) remains a high-risk multiple myeloma feature in the context of contemporary therapy and gene-expression profiling (GEP), we reviewed records of 1474 patients with myeloma, who were enrolled in Total Therapy protocols or treated identically off protocol. A total of 27 patients (1.8%) were classified as having PPCL. As a group, these patients more often had low hemoglobin, high beta-2-microglobulin, high lactate dehydrogenase, low albumin and cytogenetic abnormalities. Among 866 patients with GEP results, the PPCL group more often had disease that was classified as high risk, and in CD-1 and MF molecular subgroups. Regardless of the therapeutic protocol, patients with PPCL had shorter median overall survival (OS; 1.8 years), progression-free survival (PFS; 0.8 years) and complete response duration (CRD; 1.3 years) than the remainder, whose clinical outcomes had improved markedly with successive protocols. Multivariate analyses of pretreatment parameters showed that PPCL was a highly significant independent adverse feature linked to OS, PFS and CRD. In GEP analyses, 203 gene probes distinguished PPCL from non-PPCL; the identified genes were involved in the LXR/RXR activation, inositol metabolism, hepatic fibrosis/hepatic stellate-cell activation and lipopolysaccharide/interleukin-1-mediated inhibition of RXR function pathways. Different treatment approaches building on these genomic differences may improve the grave outcome of patients with PPCL.

A multi-state Salmonella Typhimurium outbreak associated with frozen vacuum-packed rodents used to feed snakes.

From December 2005 through January 2006, the Minnesota Department of Health (MDH) identified four human clinical isolates of Salmonella Typhimurium that were indistinguishable by pulsed-field gel electrophoresis (PFGE). During routine interviews, three of the cases reported attending the same junior high school and two handled snakes in the science classroom. MDH collected environmental samples from the school's science classroom for Salmonella culturing; these included environmental samples and frozen vacuum-packed mice purchased over the internet to feed the classroom snakes. Through PulseNet, a national molecular subtyping surveillance network for enteric bacteria, 21 human S. Typhimurium isolates with indistinguishable PFGE patterns were identified in the United States since December 2005. Each state determined whether these human cases had recent exposure to snakes fed vacuum-packed rodents. Texas state officials conducted tracebacks of the vacuum-packed mice and collected samples at the breeding facility. Nineteen of 21 cases were interviewed, and seven reported contact with frozen vacuum-packed rodents from the same internet-based supplier in Texas. In Minnesota, the outbreak PFGE subtype of S. Typhimurium was isolated from the snakes, frozen feed rodents, and the classroom environment. Three human cases were identified in Michigan, Pennsylvania, and Wyoming. The outbreak PFGE subtype of S. Typhimurium was isolated from the Pennsylvania case's frozen rodents and the Michigan case's pet snake. The outbreak PFGE subtype of S. Typhimurium was also isolated from the supplier's rodent facility. This was a S. Typhimurium outbreak associated with frozen rodents. Human transmission likely occurred through direct contact with snakes and contaminated environmental surfaces. This report represents the second recent multi-state salmonellosis outbreak associated with commercially distributed rodents. Stronger oversight of the commercial rodent industry is warranted.

Long-term results show triple stapling facilitates safe low colorectal and coloanal anastomosis and is associated with low rates of local recurrence after anterior resection for rectal cancer.

BACKGROUND: During low anterior resection (AR), placement of a staple line distal to an occlusion clamp is often difficult due to the confines of a narrow bony pelvis. This study reviewed the results of AR with a technique in which a linear staple line is fired below the tumour as an oncologically safe occlusion clamp. METHODS: Between 1995 and 2000, a total of 174 patients were operated for rectal cancer, and 153 of these patients had AR. Triple stapling (TS) was used to place a line of staples that occluded the fully mobilised rectum below a tumour. After rectal washout, a further linear stapler was applied below the first, and the rectum was divided prior to a standard circular stapled anastomosis. RESULTS: TS was performed in 127 (83%) of 153 patients undergoing AR, and 9 TS patients developed leaks (7%). In the whole series of 174 cases, 9 patients had local recurrence (5%), but the local recurrence rate for procedures classified as 'locally curative' was 2%. CONCLUSIONS: Triple stapling reliably occludes the rectum allowing for distal rectal washout. It eliminates clamp slippage and faecal spillage and improves access to the distal rectum for low anastomoses.

Operability and early outcome in 100 consecutive laparotomies for peritoneal malignancy.

BACKGROUND: Peritoneal malignancy is common at the terminal stages of many intra-abdominal neoplasms. In selected patients a novel approach of complete macroscopic tumour removal by extensive surgical cytoreduction, combined with intraperitoneal chemotherapy, provides a possibility of cure. Initial experience with 100 consecutive laparotomies is reported. METHODS: Between 1994 and 2002, 218 patients with peritoneal malignancy were referred to a specialized unit. One hundred underwent laparotomy, of whom 85 had a primary appendiceal tumour. Treatment aims were complete macroscopic tumour excision combined with intraoperative intraperitoneal chemotherapy. RESULTS: Sixty-five patients had complete macroscopic tumour excision, 28 palliative major cytoreduction and seven were inoperable. The overall mortality rate was 8 per cent. The most common complications were pulmonary (25 per cent) and wound (14 per cent) infection. At a median follow-up of 30 (range 3-113) months, 44 of 51 patients with primary appendiceal tumours who had complete macroscopic cytoreduction were alive and 36 were disease free. CONCLUSION: Cytoreduction combined with intraperitoneal chemotherapy is an emerging technique with promising results in selected patients with peritoneal malignancy.

Elevated tumour markers prior to complete tumour removal in patients with pseudomyxoma peritonei predict early recurrence.

OBJECTIVE: To assess the potential value of pre-operative CEA, CA 125 and CA 19-9 in identifying Pseudomyxoma peritonei (PMP) patients at risk of recurrence following complete cytoreductive surgery and intraperitoneal chemotherapy. METHOD: Between March 1996 and October 2001, 35 patients, with documented pre-operative tumour marker measurements, underwent complete cytoreduction. Outcome in the 32 survivors was recorded. RESULTS: Median age was 53 years (range: 32-74). There were 17[53%] females. In 9/32[28%] all tumour markers were normal. The most common abnormality was elevated CEA level in 14/32[44%]. Median follow up was 23 months (range: 11-74). Recurrence was detected in 8/32[25%]. The 2-year recurrence free interval was 53% in those with elevated CEA compared with 94% with normal CEA. The 2-year disease free intervals were 100% in 9 patients with normal preop markers compared with 66% for the group with at least one abnormal marker. CONCLUSION: PMP patients with elevated CEA, or more than one abnormal serum tumour maker, are at risk of developing recurrent disease.

Almost all five year disease free survivors are cured following rectal cancer surgery, but longer term follow-up detects some late local and systemic recurrences.

BACKGROUND: The necessity, timing and benefits of follow-up after rectal cancer surgery remain controversial, with two years traditionally considered adequate to detect most local recurrences. This unit has a policy of lifetime follow-up, and this paper investigates, at 23 years, the value of prolonged surveillance. METHOD: Six hundred and sixty consecutive patients undergoing surgery for rectal cancer were prospectively followed-up between 1978 and 2002, and local or systemic recurrence recorded. This analysis was performed on the 509/660 (76%) patients who underwent potentially curative surgery. RESULTS: Total mesorectal excision (TME) was performed in 422/509 (83%) patients, mesorectal transection in 78 (15%), and local excision in 9 (2%). Follow-up ranged from 1 to 23 years (mean = 9.7). Seven (1.4%) patients had local recurrence alone, 11 (2.2%) local plus systemic, and 86 (17%) systemic recurrence alone. Of the local recurrences 3 (17%) became evident within 1 year, 9 (50%) within 2 years, 16 (89%) within 5 years, and 2 (11%) presented after 5 years, at 5.6 and 5.8 years. Of the systemic recurrences 26 (27%) became evident within 1 year, 57 (59%) within 2 years, 93 (96%) within 5 years, and 4 (4%) presented after 5 years at 5.3, 5.3, 5.4 and 7.9 years. CONCLUSION: This long-term surveillance of patients undergoing curative surgery for rectal cancer demonstrates that most local and systemic recurrences occur within 5 years. Almost half occurred more than 2 years after surgery. However, those centres wishing to set standards of care, or evaluate current or new therapies in rectal cancer treatment, should be aware that unexpected late recurrences occasionally develop.

Optimal preoperative assessment and surgery for rectal cancer may greatly limit the need for radiotherapy.

BACKGROUND: Radiation is being used increasingly in the management of patients with rectal cancer. Over the past decade the Basingstoke Colorectal Research Unit has combined precision total mesorectal excision with the highly selective use of preoperative radiotherapy. METHODS: One hundred and fifty consecutive patients who underwent major surgical excision for cancers of all stages comprised the study group. Preoperative clinical assessment was based largely on tumour size, fixation and distance from the anal verge. Only preoperative radiotherapy was considered and this only for tumours judged to be at high risk of mesorectal fascia involvement. RESULTS: During a 5-year period 35 of 150 patients were selected for preoperative irradiation. In the non-irradiated patients the local recurrence rate after a median follow-up period of 870 (range 51-1903) days was 2.6 per cent (three of 115 patients), compared with 17.1 per cent (six of 35 patients) in those chosen for irradiation. Sixty patients (52.2 per cent) who were not irradiated were node positive. The local recurrence rate for the whole group was 6.0 per cent. CONCLUSION: The great majority of patients undergoing major excision for rectal cancer can be managed without radiation therapy if the preoperative assessment of the mesorectal fascia and surgery are performed optimally.

A 5-cm colonic J pouch colo-anal reconstruction following anterior resection for low rectal cancer results in acceptable evacuation and continence in the long term.

BACKGROUND: Optimal treatment for low rectal cancer is total mesorectal excision, with most patients suitable for low colo-rectal or colo-anal anastomosis. A colon pouch has early functional benefits, although long-term function, especially evacuation, might mitigate against its routine use. The aim of this study was to assess evacuation and continence in patients with a colon pouch, and to examine the impact of possible risk factors. METHODS: In 1998, all 102 surviving patients with a colon pouch, whose stoma had been closed for more than one year, were sent a postal questionnaire. A composite incontinence score was calculated from questions on urgency, use of a pad, incontinence of gas, liquid or faeces; and a composite evacuation score from questions on medication taken to evacuate, straining, the need and number of times returned to evacuate. RESULTS: The response rate was 90% (50 M, 42 F), with a median age of 68 years (IQR 60-78) and median follow-up of 2.6 years (IQR 1.7-3.9). The anastomosis was 3 cm or less from the anus in 45/92 (49%), and incontinence scores were worse in this group (P = 0.001). There were significantly higher incontinence scores in females (P = 0.014). Age, preoperative radiotherapy, part of colon used for anastomosis, postoperative leak and length of follow-up had no demonstrable effect on either score. CONCLUSION: Gender and anastomotic height were the only variables which influenced incontinence. Ninety percent of patients reported that their bowel function did not affect their overall wellbeing, and none would have preferred to have a stoma.

Caspase-9 activation in hypoxic human corneal epithelial cells.

The purpose of this study was to determine the effect of hypoxia on caspase-8 and -9 gene and protein expression and activity in corneal epithelium. Non-transformed human corneal epithelial cells (HCEC) were cultured in 2% oxygen. A cDNA expression array coupled with densitometric analysis was used to compare relative mRNA expression levels of 96 apoptosis-related genes in hypoxic and normoxic HCEC. Caspase-8, caspase-9, FLIP, Fas, FasL, and TNFalpha protein expression was assessed further using Western blot analysis and ELISA. Caspase-8 and -9 activities were measured using a fluorometric activity assay. Hypoxia did not affect caspase-8 or -9 gene or protein expression in HCEC, however caspase-9 activity was significantly increased. Hypoxia significantly suppressed the activity of caspase-8. FLIP and Fas gene and protein expression were not significantly altered in hypoxic cells compared to normoxic controls. mRNA and protein levels of TNFalpha and TNFR-1 were significantly decreased, while FasL mRNA and proteins levels were significantly increased in hypoxic HCEC. In corneal epithelium stressed by hypoxia caspase-9 activity is upregulated, suggesting that apoptosis proceeds via the mitochondrial pathway. Caspase-8 activity may be suppressed because the loss of TNFalpha and TNFR-1 gene and protein expression inhibits the initial formation of a death signaling complex.

Aspirin in cardiovascular disease.

The historic genesis of aspirin as a therapeutic agent is discussed. The use of aspirin as a primary and secondary chemo-preventive agent is reviewed. Those who introduced aspirin in the late 19th century would be surprised by the uses of aspirin today. It is anticipated that existing and further studies on the use of aspirin as a primary preventive agent will establish its utility and a more precise niche for it as a chemo-preventive agent. Reports indicate that it may be useful as a chemo-preventive agent in the prevention and possibly in the treatment of cancer of the colon and other malignancies. This plebeian drug, aspirin, has earned a position, some would say an egalitarian position, along with thrombolysis and primary coronary angioplasty in the emergency treatment of AMI. There are those who would add an intravenous beta blocker and an ACE inhibitor to this regimen. The laborious history of aspirin should again remind clinicians that they should continue to heed the admonition of Alexander Pope when he asserted, "Be not the first by whom the new is tried nor yet the last to lay the old aside."

Stoma-related complications are more frequent after transverse colostomy than loop ileostomy: a prospective randomized clinical trial.

BACKGROUND: The consequences of leakage from low colorectal or coloanal anastomoses are reduced by the use of a loop stoma to divert the faecal stream. Controversy continues as to whether loop ileostomy (LI) or loop transverse colostomy (LTC) is the optimal method of defunctioning such anastomoses. METHODS: Patients requiring defunctioning following anterior resection and total mesorectal excision were randomized to receive either LI or LTC. Comparison was made between the groups regarding the difficulty of stoma formation and closure, the recovery after stoma closure and stoma-related complications. The minimum follow-up after stoma closure was 6 months (median 36 months). RESULTS: Between October 1995 and August 1999, 70 patients were randomized (LTC 36, LI 34) of whom 63 underwent stoma closure (LTC 31, LI 32). There were no significant differences in the difficulty of formation or closure, or in the postoperative recovery between the groups. However, there were ten complications related directly to the stoma in the LTC group: faecal fistula (one patient), prolapse (two), parastomal hernia (two) and incisional hernia during follow-up (five). None of these complications occurred in the LI group. CONCLUSION: In this randomized study, the frequency of herniation before or after colostomy closure supports the choice of LI as a method of defunctioning a low anastomosis. Both methods appear to provide satisfactory protection for the low anastomosis.

Analysis of gene promoters for two tomato polygalacturonases expressed in abscission zones and the stigma.

The tomato (Lycopersicon esculentum cv Ailsa Craig) polygalacturonase genes TAPG1 (LYCes;Pga1;2) and TAPG4 (LYCes;Pga1;5) are abundantly expressed in both abscission zones and the pistils of mature flowers. To further investigate the spatial and temporal expression patterns for these genes, the TAPG gene promoters were ligated to beta-glucuronidase (GUS) reporter genes and transformed into tomato. GUS expression with both constructs was similar and entirely consistent with the expression patterns of the native gene transcripts. GUS activity was observed in the weakening abscission zones of the leaf petiole, flower and fruit pedicel, flower corolla, and fruit calyx. In leaf petiole and flower pedicel zones this activity was enhanced by ethylene and inhibited by indole-3-acetic acid. On induction of abscission with ethylene, GUS accumulation was much earlier in TAPG4:GUS than in TAPG1:GUS transformants. Moreover, TAPG4:GUS staining appeared to predominate in the vascular bundles relative to surrounding cortex cells whereas TAPG1:GUS was more evenly distributed across the separation layer. Like the native genes, GUS was also expressed in the stigma. Activity was not apparent in pistils until the flowers had opened and was confined to the stigma and style immediately proximal to it. A minimal promoter construct consisting of a 247-bp 5'-upstream element from TAPG1 was found to be sufficient to direct GUS expression in both abscission zones and the stigma.

Outcomes of primary phakic trabeculectomies without versus with 0.5- to 1-minute versus 3- to 5-minute mitomycin C.

PURPOSE: To compare the intraocular pressure and hypotony outcomes of primary phakic trabeculectomies with no mitomycin C (MMC), shorter MMC, and longer MMC exposure. METHODS: We evaluated primary phakic trabeculectomies with no MMC (36 eyes of 36 patients), 0.5- to 1-minute MMC (50 eyes of 50 patients), and 3- to 5-minute MMC (38 eyes of 38 patients) at the concentration of 0.5 mg/ml. Successful trabeculectomy was defined as an intraocular pressure of 21 mm Hg or less without development of a marked visual acuity loss associated with prolonged hypotony (intraocular pressure < 6 mm Hg over 3 months) and without the need for additional surgery to control intraocular pressure or treat postoperative complications. RESULTS: The three groups were similar in demographics, preoperative intraocular pressure, and medical dependency. However, the incidence of hypotony during the postoperative periods of 3 to 12 months was significantly higher in the 3- to 5-minute MMC group (P < .05, chi-square test). Severe visual acuity loss associated with hypotony was also more frequently found in the 3- to 5-minute MMC group than in the 0.5- to 1-minute (P = .009, chi-square test) group or the control group (P = .014, chi-square test). In addition, the success probabilities were significantly different among the three groups (P = .001, Kaplan-Meier survival analysis with log-rank test) and were the highest in the 0.5- to 1-minute MMC group and the lowest in the 3- to 5-minute MMC group. CONCLUSION: Shorter application (0.5 to 1 minute) of MMC appears to be optimal for the successful outcome of primary phakic trabeculectomy compared with no MMC or longer application of MMC at a concentration of 0.5 mg/ml.