Relationship Between Spiritual Coping and Survival in Patients with HIV

BACKGROUND

Studies of spirituality in initially healthy people have shown a survival advantage, yet there are fewer research studies in the medically ill, despite the widespread use of spirituality/religiousness to cope with serious physical illness. In addition, many studies have used limited measures such as religious service attendance.

OBJECTIVE

We aimed to examine if, independent of medication adherence, the use of spirituality/religiousness to cope with HIV predicts survival over 17 years.

DESIGN

This was a longitudinal study, started in 1997. Study materials were administered semi annually.

PARTICIPANTS

A diverse sample of 177 HIV patients initially in the mid-stage of disease (150–500 CD4-cells/mm³; no prior AIDS-defining symptoms) participated in the study.

MAIN MEASURES

Participants were administered a battery of psychosocial questionnaires and a blood draw. They completed interviews and essays to assess current stressors. Spiritual coping (overall/strategies) was rated by qualitative content analysis of interviews regarding stress and coping with HIV, and essays.

KEY RESULTS

Controlling for medical variables (baseline CD4/viral load) and demographics, Cox regression analyses showed that overall positive spiritual coping significantly predicted greater survival over 17 years (mortality HR?= 0.56, p?= 0.039). Findings held even after controlling for health behaviors (medication adherence, substance use) and social support. Particular spiritual coping strategies that predicted longer survival included spiritual practices (HR?= 0.26, p?<?0.001), spiritual reframing (HR?= 0.27, p?= 0.006), overcoming spiritual guilt (HR?= 0.24, p?<?0.001), spiritual gratitude (HR?= 0.40, p?= 0.002), and spiritual empowerment (HR?= 0.52, p?= 0.024), indicating that people using these strategies were 2–4 times more likely to survive.

CONCLUSIONS

To our knowledge this is the first study showing a prospective relationship of spiritual coping in people who are medically ill with survival over such a long period of time, and also specifically identifies several strategies of spirituality that may be beneficial.

     

Prevalence of Nausea and Vomiting in Adults Using Ropinirole: A Systematic Review and Meta-Analysis

Background

Nausea and vomiting are commonly associated with medication use. Dopaminergic agonists have been associated with these symptoms, but their impact in patients without Parkinson’s disease, such as those with restless legs syndrome (RLS), is not well characterized.

Aims

We sought to determine whether the non-ergoline dopamine agonist ropinirole is associated with nausea and vomiting in adults with RLS.

Methods

We conducted a systematic review using PUBMED, EMBASE, and clinical trial databases to identify placebo-controlled clinical trials of ropinirole for RLS treatment. We extracted data including dosing schedule and the proportion of patients reporting nausea and/or vomiting. We also determined hazard ratios (HR) using a random effects proportional hazard model.

Results

We extracted data from a pool of 13 studies. The prevalence of nausea in the ropinirole-treated RLS group (RLS-R; N = 1528) was 37.2% compared to 9.4% in the placebo-treated RLS group (RLS-P; N = 1395) (p < 0.0001). The prevalence of vomiting in the RLS-R group was 10.9% compared to 2.6% in the RLS-P group (p < 0.0001). Ropinirole use was associated with a higher risk of reporting nausea (HR 5.924 [4.410–7.959], p < 0.001) and experiencing vomiting (HR 4.628 [3.035–7.057], p < 0.0001). Nausea and vomiting represented nearly 50% of all adverse events reported.

Conclusions

Nausea and vomiting are quite common side effects in those using ropinirole for RLS. As RLS is more widely recognized and treated; the prevalence of ropinirole-induced nausea and vomiting could grow substantially. Ropinirole use should be considered as a cause of chronic nausea and vomiting.

     

Symptom Domain Groups of the Patient-Reported Outcomes Measurement Information System Tools Independently Predict Hospitalizations and Re-hospitalizations in Cirrhosis

Background

Patient-Reported Outcomes Measurement Information System (PROMIS) tools can identify health-related quality of life (HRQOL) domains that could differentially affect disease progression. Cirrhotics are highly prone to hospitalizations and re-hospitalizations, but the current clinical prognostic models may be insufficient, and thus studying the contribution of individual HRQOL domains could improve prognostication.

Aim

Analyze the impact of individual HRQOL PROMIS domains in predicting time to all non-elective hospitalizations and re-hospitalizations in cirrhosis.

Methods

Outpatient cirrhotics were administered PROMIS computerized tools. The first non-elective hospitalization and subsequent re-hospitalizations after enrollment were recorded. Individual PROMIS domains significantly contributing toward these outcomes were generated using principal component analysis. Factor analysis revealed three major PROMIS domain groups: daily function (fatigue, physical function, social roles/activities and sleep issues), mood (anxiety, anger, and depression), and pain (pain behavior/impact) accounted for 77% of the variability. Cox proportional hazards regression modeling was used for these groups to evaluate time to first hospitalization and re-hospitalization.

Results

A total of 286 patients [57 years, MELD 13, 67% men, 40% hepatic encephalopathy (HE)] were enrolled. Patients were followed at 6-month (mth) intervals for a median of 38 mths (IQR 22–47), during which 31% were hospitalized [median IQR mths 12.5 (3–27)] and 12% were re-hospitalized [10.5 mths (3–28)]. Time to first hospitalization was predicted by HE, HR 1.5 (CI 1.01–2.5, p = 0.04) and daily function PROMIS group HR 1.4 (CI 1.1–1.8, p = 0.01), independently. In contrast, the pain PROMIS group were predictive of the time to re-hospitalization HR 1.6 (CI 1.1–2.3, p = 0.03) as was HE, HR 2.1 (CI 1.1–4.3, p = 0.03).

Conclusions

Daily function and pain HRQOL domain groups using PROMIS tools independently predict hospitalizations and re-hospitalizations in cirrhotic patients.

     

Tumor characteristics associated with malignant large bowel obstruction in stage IV colorectal cancer patients undergoing chemotherapy

Purpose

Little is known about predictable clinical factors associated with the occurrence of malignant large bowel obstruction (MLBO) in incurable stage IV colorectal cancer (CRC) patients undergoing medical treatment. This study investigates the clinical characteristics associated with MLBO that occurred while patients with stage IV CRC were receiving chemotherapy.

Methods

A total of 216 patients who were diagnosed with stage IV CRC without bowel obstruction and who received chemotherapy between May 2005 and June 2012 were retrospectively included in this study. Patients were divided into an “obstruction group” and a “non-obstruction group” based on whether they did or did not develop MLBO during chemotherapy or follow-up, respectively. The initial endoscopic findings and clinical information were retrospectively reviewed and compared between the two groups.

Results

Forty-six patients (21.3 %) developed MLBO during the treatment or follow-up periods. The mean duration between diagnosis and MLBO was 9.8 ± 9.3 months. After adjusting for clinically relevant factors, MLBO development was independently associated with the following factors: higher initial tumor-occupying circumference (HR 1.030 [95 % CI, 1.012–1.049], P = 0.001), longer initial horizontal tumor width (HR 1.035 [95 % CI, 1.011–1.059], P = 0.004), primary tumor location at a turning point in the colon (HR 2.404 [95 % CI, 1.185–4.877], P = 0.015), and the presence of primary tumor ulceration at presentation (HR 3.767 [95 % CI, 1.882–7.538], P < 0.001). MLBO development was not associated with tumor response to chemotherapy.

Conclusion

In patients with stage IV CRC, MLBO development during chemotherapy treatment is associated with tumor ulceration, location, circumference, and width at diagnosis.

     

Risk factors and outcomes of acute lower gastrointestinal bleeding in intestinal Behçet’s disease

Background

Intestinal Behçet’s disease (BD) can cause acute lower gastrointestinal bleeding, which is sometimes fatal.

Aim

We aimed to identify the risk factors and outcomes of acute lower gastrointestinal bleeding and factors associated with rebleeding in intestinal BD patients.

Methods

Of the total of 588 intestinal BD patients, we retrospectively reviewed the medical records of 66 (11.2%) patients with acute lower gastrointestinal bleeding and compared them with those of 132 matched patients without bleeding.

Results

The baseline characteristics were comparable between the bleeding group (n = 66) and the non-bleeding group (n = 132). On multivariate analysis, the independent factors significantly associated with lower gastrointestinal bleeding were older age (>52 years) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.058–4.684, p = 0.035) and a nodular ulcer margin (HR 7.1, 95% CI 2.084–24.189, p = 0.002). Rebleeding occurred in 23 patients (34.8%). Female patients (p = 0.044) and those with previous use of corticosteroids or azathioprine (p = 0.034) were more likely to develop rebleeding. On multivariate analysis, only use of steroids or azathioprine was significantly associated with rebleeding (HR 3.2, 95% CI 1.070–9.462, p = 0.037).

Conclusions

Age >52 years and the presence of a nodular margin of the ulcer were found to be related to increased risk of bleeding in patients with intestinal BD. Rebleeding is not uncommon and not effectively prevented with currently available medications. Further studies are warranted to identify effective measures to decrease rebleeding in intestinal BD.

     

Preoperative patient-related factors associated with prognosis after esophagectomy for esophageal cancer

Background

To investigate the impact of the preoperative patient-related factors on survival after esophagectomy in patients with esophageal cancer.

Methods

We retrospectively reviewed 140 patients with esophageal cancer who underwent esophagectomy. Preoperative comorbidities, nutritional and inflammation status including the neutrophil to lymphocyte ratio and Glasgow prognostic score (GPS), and their pathological findings were analyzed to assess their relationships with prognosis.

Results

Univariate analysis demonstrated that a history of cardiovascular disease (CVD), a GPS of 1 or 2, lack of neo-adjuvant chemotherapy (NAC), no thoracoscopic esophagectomy, blood loss volume ≥255 ml, the number of lymph node metastasis (LNM) ≥2, lymphatic invasion, venous invasion, and residual cancer were associated with poor survival. Multivariate analysis revealed that a history of CVD [hazard ratio (HR) 2.129; 95% confidence interval (CI) 1.327–4.226; P = 0.041], a GPS of 1 or 2 (HR 3.232; 95% CI 1.516–6.437; P = 0.003), LNM ≥2 (HR 3.133; 95% CI 1.355–7.760; P = 0.007), and pathological residual cancer (HR 2.429; 95% CI 1.050–5.105; P = 0.039) were independently associated with poor survival, and NAC was associate with better survival (HR 0.289; 95% CI 0.118–0.667; P = 0.003).

Conclusions

Preoperative patient-related factors including a history of CVD and a GPS of 1 or 2 were predictors of poor prognosis after esophagectomy in patients with esophageal cancer.

     

Statin Use,Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients

BACKGROUND

The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk.

OBJECTIVE

We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG).

DESIGN AND PARTICIPANTS

Observational cohort study of 13,508 normoglycemic patients (n?=?4460; 33 % taking statins) and 4563 IFG patients (n?=?1865; 41 % taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999–2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan–Meier method.

MAIN MEASURES

The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality.

KEY RESULTS

After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95 % CI, 1.05 to 1.35; p?=?0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p?=?0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95 % CI, 0.66 to 0.80; p?<?0.0001) and IFG patients (HR 0.77, 95 % CI, 0.64 to 0.91; p?=?0.0029) with statin use.

CONCLUSION

In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19–24 %) risk.

     

Left atrial appendage exclusion during mitral valve surgery and stroke in atrial fibrillation

Purpose

The purpose of this study was to determine whether surgical left atrial appendage (LAA) exclusion performed during mitral valve surgery is associated with a reduction in cerebrovascular events in patients with atrial fibrillation.

Methods

We retrospectively studied patients with atrial fibrillation who underwent mitral valve surgery from 1/1/2001 through 12/31/2014. We screened 1352 patients using ICD-9 codes and included 281 patients in the study. The primary end point was a composite of strokes and transient ischemic attacks occurring within 5 years after surgery. Secondary end points were stroke, transient ischemic attack, and all-cause mortality.

Results

The LAA exclusion group (n?=?188) had a lower prevalence of female gender, hypertension, and diabetes mellitus compared with the non-LAA exclusion group (n?=?93). The CHA₂DS₂VASc scores were comparable between groups (2.6 vs 2.9, P?=?.11), as was anticoagulant use (82.4% vs 85.0%, P?=?.60). Concomitant surgical ablation was performed in 73.9% of patients who underwent LAA exclusion. Nine cerebrovascular events occurred in the LAA exclusion group and 13 in the non-LAA exclusion group (HR 0.30 [0.12–0.75], P?=?.01). There was no difference in all-cause mortality between groups. On multivariate analysis of the primary end point of strokes or transient ischemic attacks, significant variables were LAA exclusion (HR 0.31 [0.12–0.76], P?=?.01) and CHA₂DS₂VASc score (HR 1.44 [1.11–1.87], P?=?.006). The benefit of LAA exclusion was detected only when performed together with surgical ablation (HR 0.27 [0.09–0.72], P?=?.01).

Conclusions

LAA exclusion was associated with fewer cerebrovascular events. However, this benefit was seen only with concomitant surgical ablation.

     

Impact of residual urine volume decline on the survival of chronic hemodialysis patients in Kinshasa

Background

Despite the multiple benefits of maintaining residual urine volume (RUV) in hemodialysis (HD), there is limited data from Sub-Saharan Africa. The aim of this study was to assess the impact of RUV decline on the survival of HD patients.

Methods

In a retrospective cohort study, 250 consecutive chronic HD patients (mean age 52.5 years; 68.8% male, median HD duration 6 months) from two hospitals in the city of Kinshasa were studied, between January 2007 and July 2013. The primary outcome was lost RUV. Preserved or lost RUV was defined as decline RUV?<?25 (median decline) or?≥?25 ml/day/month, respectively. The second endpoint was survival (time-to death). Survival curves were built using the Kaplan-Meier methods. We used Log-rank test to compare survival curves. Predictors of mortality were assessed by Cox proportional hazards regression models.

Results

The cumulative incidence of patients with RUV decline was 52, 4%. The median (IQR) decline in RUV was 25 (20.8–33.3) ml/day/month in the population studied, 56.7 (43.3–116.7) in patients deceased versus 12.9 (8.3–16.7) in survivor patients (p?<?0.001). Overall mortality was 78 per 1000 patient years (17 per 1000 in preserved vs 61 per 1000 lost RUV). Forty six patients (18.4%) died from withdrawal of HD due to financial constraints. The Median survival was 17 months in the whole group while, a significant difference was shown between lost (10 months, n?=?119) vs preserved RUV group (30 months, n?=?131; p?=?0001). Multivariate Cox proportional hazards models showed that, decreased RUV (adjusted HR 5.35, 95% CI [2.73–10.51], p?<?0.001), financial status (aHR 2.23, [1.11–4.46], p?=?0.024), hypervolemia (a HR 2.00, [1.17–3.40], p?=?0.011), lacking ACEI (aHR 2.48, [1.40–4.40], p?=?0.002) or beta blocker use (aHR 4.04, [1.42–11.54], p?=?0.009), central venous catheter (aHR 6.26, [1.71–22.95], p?=?0.006), serum albumin (aHR 0.93, [0.89–0.96], p?<?0.001) and hemoglobin (aHR 0.73, [0.63–0.84], p?<?0.001) had emerged as the independent predictors of all-cause mortality.

Conclusion

More than half of HD patients in this cohort study experienced fast RUV decline which contributed substantially to increase mortality, highlighting the need for its prevention and management.

     

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study—The Importance of Pathological N Status,More Than We Thought

Background

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Methods

We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors.

Results

TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72–8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77–5.26), p < 0.0001], and higher SUV_max [HR 4.33 (95% CI 1.03–7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13–18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85–10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01–1.20), p = 0.047]; and SUV_max [HR 1.83 (95% CI 1.04–3.23), p = 0.035].

Conclusion

Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUV_max.

     

Type 1 diabetic patients with peripheral neuropathy have pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile

Aims/hypothesis

We hypothesised that type 1 diabetic patients with established diabetic sensorimotor polyneuropathy (DSPN) would have segmental and/or pan-enteric dysmotility in comparison to healthy age-matched controls. We aimed to investigate the co-relationships between gastrointestinal function, degree of DSPN and clinical symptoms.

Methods

An observational comparison was made between 48 patients with DSPN (39 men, mean age 50 years, range 29–71 years), representing the baseline data of an ongoing clinical trial (representing a secondary analysis of baseline data collected from an ongoing double-blind randomised controlled trial investigating the neuroprotective effects of liraglutide) and 41 healthy participants (16 men, mean age 49 years, range 30–78) who underwent a standardised wireless motility capsule test to assess gastrointestinal transit. In patients, vibration thresholds, the Michigan Neuropathy Screening Instrument and Patient Assessment of Upper Gastrointestinal Symptom questionnaires were recorded.

Results

Compared with healthy controls, patients showed prolonged gastric emptying (299?±?289 vs 179?±?49 min; p?=?0.01), small bowel transit (289?±?107 vs 224?±?63 min; p?=?0.001), colonic transit (2140, interquartile range [IQR] 1149–2799 min vs 1087, IQR 882–1650 min; p?=?0.0001) and whole-gut transit time (2721, IQR 1196–3541 min vs 1475 (IQR 1278–2214) min; p?<?0.0001). Patients also showed an increased fall in pH across the ileocaecal junction (?1.8?±?0.4 vs ?1.3?±?0.4 pH; p?<?0.0001), which was associated with prolonged colonic transit (r?=?0.3, p?=?0.001). Multivariable regression, controlling for sex, disease duration and glycaemic control, demonstrated an association between whole-gut transit time and total GCSI (p?=?0.02).

Conclusions/interpretation

Pan-enteric prolongation of gastrointestinal transit times and a more acidic caecal pH, which may represent heightened caecal fermentation, are present in patients with type 1 diabetes. The potential implication of delayed gastrointestinal transit on the bioavailability of nutrition and on pharmacotherapeutic and glycaemic control warrants further investigation.

Trial registration

EUDRA CT: 2013-004375-12

     

Self-expandable metallic stent as a bridge to elective surgery versus emergency surgery for acute malignant colorectal obstruction

Backgroud

The efficacy and safety of self-expandable metallic stents (SEMSs) as a bridge for patients with acute malignant colorectal obstructions (AMCOs) are still controversial. We conducted this study to evaluate the outcomes of patients with AMCOs treated by different strategies.

Methods

From January 2010 to March 2014, a total of 171 patients with AMCOs from Zhongshan Hospital were retrospectively enrolled in this study. One hundred twenty patients successfully received stent placement followed by one-stage laparoscopic or open resection in the stent group, and 51 patients received emergency operations in the emergency group.

Results

The operation duration and postoperative hospital stay were significantly shorter in the stent group (114.51?±?28.65 vs. 160.39?±?58.94 min, P?<?0.001; 8.00?±?3.97 vs. 12.59?±?9.07 days, P?=?0.001). The stent group also had significantly reduced intraoperative blood loss and the incidence of postoperative complications compared with the emergency group (61.00?±?43.70 vs. 121.18?±?85.90 ml, P?<?0.001; 16.7 vs. 37.3 %, P?=?0.003). Kaplan–Meier survival curves showed that the median survival time in the stent group was significantly longer than that in the emergency group (53 vs. 41 months, P?=?0.034). In subgroup analysis of stent group, the stent laparoscopy group had significantly decreased postoperative complications (P?=?0.025), and similar long-term survival (P?=?0.81).

Conclusions

Stent placement as a bridge to surgery is a safe and feasible procedure and provides significant advantages in terms of short-term outcomes and favorable prognoses for patients with AMCOs. Laparoscopic surgery could be considered as an optimal treatment after stent placement.

     

Macroscopic serosal invasion and small tumor size as independent prognostic factors in stage IIA colon cancer

Background

This study aimed to investigate the prognostic factors of patients with stage IIA (T3N0M0) colon cancer in terms of macroscopic serosal invasion and small tumor size.

Methods

We enrolled 375 stage IIA colon cancer patients who underwent curative resection between January 2004 and December 2011. Macroscopic serosal invasion was defined as tumor nodules or colloid changes protruding the surface of the serosa. The clinicopathologic characteristics were analyzed to identify independent prognostic factors.

Results

The median follow-up was 47 months (range, 1–90 months). On multivariate survival analysis, macroscopic serosal invasion (adjusted hazard ratio [HR]?=?4.750; p?=?0.013), tumor size <?5 cm (adjusted HR?=?3.112, p?=?0.009), perineural invasion (adjusted HR?=?3.528; p?=?0.002), <?12 retrieved lymph nodes (adjusted HR?=?4.257; p?=?0.002), and localized perforation (adjusted HR?=?7.666; p?=?0.008) were independent risk factors for recurrence.

Conclusion

We found novel prognostic factors of stage IIA colon cancer, including macroscopic serosal invasion and small tumor size (<?5 cm). Further studies are needed to evaluate the benefit of adjuvant chemotherapy in patients with these prognostic factors.

     

Diabetes was the only comorbid condition associated with mortality of invasive pneumococcal infection in ICU patients: a multicenter observational study from the Outcomerea research group

Purposes

Streptococcus pneumoniae is a leading pathogen of severe community, hospital or nursing facility infections. We sought to describe characteristics of invasive pneumococcal infection (IPI) and pneumonia (due to the high mortality of intensive care-associated pneumonia) and to report outcomes according to various types of comorbidity.

Methods

Multicenter observational cohort study on the prospective Outcomerea database, including adult patients, with a hospital stay?<?48 h before ICU admission and a documented IPI within the first 72 h of ICU admission. Comorbid conditions were defined according to the Knaus and Charlson classification.

Results

Of the 20,235 patients, 5310 (26.4%) had an invasive infection, including 560/5,310 (10.6%) who had an IPI. The ICU 28-day mortality was 109/560 (19.8%). Four factors were independently associated with mortality: SOFA day 1–2: [hazard ratio (HR) 1.21; 95% confidence interval (95% CI) 1.15–1.27, p?<?0.001]; maximum lactate level day 1–2: (HR 1.07, 95% CI 1.02–1.12, p?=?0.006); diabetes mellitus: (HR 1.91, 95% CI 1.23–3.03, p?=?0.006) and appropriate antibiotics (HR 0.28, 95% CI 0.15–0.50, p?<?0.001). Comparable results were obtained when other comorbid conditions were forced into the model. Diabetes impact was more pronounced in case of micro- or macro-angiopathy (HR 4.17, 95%CI 1.68–10.54, p?=?0.003), in patients?≥?65 years old (HR 2.59, 95% CI 1.56–4.28, <?0.001) and in those with body mass index (BMI)?<?25 kg/m² (HR 2.11, 95% CI 1.10–4.06, p?=?0.025).

Conclusions

Diabetes mellitus was the only comorbid condition which independently influenced mortality in patients with IPI. Its impact was more pronounced in patients with complications, aged?≥?65 years and with BMI?<?25 kg/m².

     

Poor prognosis of young patients with colorectal cancer: a retrospective study

Purpose

The present study aimed to explore the survival outcomes of patients with colorectal cancer (CRC) aged 35 years and younger.

Methods

This retrospective cohort study included a total of 995 patients with CRC treated between January 2003 and September 2011. The patients were assorted into the young (aged 18–35 years) and older (aged 36–75 years) groups. The clinical characteristics and survival outcomes of the patients in the young group were compared with those of the patients in the older group for evaluation.

Results

Compared with the older group, a significantly higher number of patients in the young group had right-sided colon cancer (30.9 vs. 19.6%, P = 0.026), high histologic grade tumor (14.7 vs. 6.4%, P = 0.021), and stage III disease (50.0 vs. 35.5%, P = 0.016). In stage III disease, compared with the older group, the patients in the young group had worse survival outcome in terms of 5-year overall survival (OS, P = 0.007), cancer-specific survival (CSS, P = 0.010), and disease-free survival (DFS, P = 0.039). Multivariate analysis revealed that age ≤35 years was an independent risk factor in terms of 5-year OS (hazard ratio [HR] = 1.68; 95% confidence interval [CI]: 1.12–2.54; P = 0.012), CSS (HR = 1.74; 95% CI: 1.15–2.65; P = 0.009), and DFS (HR = 1.58; 95% CI: 1.06–2.35; P = 0.024).

Conclusions

The young patients with CRC aged 35 years and younger had worse prognosis compared with older patients, especially for stage III disease.

     

Short- and long-term outcomes after colorectal anastomotic leakage is affected by surgical approach at reoperation

Background

Anastomotic leakage is the most serious surgical complication following colorectal resection, and surgical intervention is often required. The purpose of the study was to investigate short- and long-term outcomes after reoperation for anastomotic leakage.

Method

Patients with a symptomatic anastomotic leakage following a laparoscopic colorectal cancer resection from January 2009 to December 2014 were identified from our local prospective database. Patients were grouped according to the management of anastomotic leaks: local, lap, or open approach. Primary outcomes were length of stay, chance of bowel continuity, and overall mortality.

Results

A total of 113 patients were included. The median follow-up time was 40 months (0–82 months). Overall mortality was significantly associated with UICC stage III–VI disease (vs. UICC stage I–II disease) [adj. HR 5.35 (CI 2.32–12.4), p?=?0.0001] and minimal invasive reoperation compared with open approach [local: adj. HR 0.12 (CI 0.03–0.52), p?=?0.004; lap: adj. HR 0.32 (CI 0.12–0.86), p?=?0.024]. Chance of bowel continuity was significantly increased in younger patients below 67 years [adj. OR 6.15 (1.76–21.5), p?=?0.004] and following a local procedure [adj. OR 7.45 (1.07–51.8), p?=?0.043]. Patients in the open group had significantly longer length of stay and time to initiation of adjuvant chemotherapy compared with those in the lap group.

Conclusion

Our data confirms that minimal invasive reoperation for anastomotic leakage is a safe and feasible approach associated with short- and long-term advantages and can be chosen in selected cases.

     

Plasma branched chain/aromatic amino acids,enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

Aims/hypothesis

Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial.

Methods

We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n?=?273), a MedDiet+nuts (n?=?324) or a control diet (n?=?295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial.

Results

Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend?=?0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD?=?1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p?= 0.005 vs the control group).

Conclusions/interpretation

Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence.Clinical trial number: SRCTN35739639 (www.controlled-trials.com)

     

Optimal duration of antimicrobial therapy for uncomplicated Gram-negative bloodstream infections

Purpose

Optimal antimicrobial treatment duration for Gram-negative bloodstream infection (BSI) remains unclear. This retrospective cohort study examined effectiveness of short (7–10 days) and long (>10 days) courses of antimicrobial therapy for uncomplicated Gram-negative BSI.

Methods

Hospitalized adults with uncomplicated Gram-negative BSI at Palmetto Health hospitals in Columbia SC, USA from January 1, 2010 to December 31, 2013 were identified. Multivariate Cox proportional hazards regression with propensity score adjustment was used to examine risk of treatment failure in the two groups.

Results

During the study period, 117 and 294 patients received short and long courses of antimicrobial therapy for uncomplicated Gram-negative BSI, respectively. Overall, the median age was 67 years, 258 (63%) were women, 282 (69%) had urinary source of infection, and 271 (66%) had BSI due to Escherichia coli. The median duration of antimicrobial therapy was 8.5 and 13.3 days in the short and long treatment groups, respectively. After adjustment for the propensity to use a short course of therapy, risk of treatment failure was higher in patients receiving short compared to long courses of antimicrobial agents (HR 2.60, 95% CI: 1.20–5.53, p = 0.02). Other risk factors for treatment failure included liver cirrhosis (HR 5.83, 95% CI: 1.89–15.02, p = 0.004) and immune compromised status (HR 4.30, 95% CI: 1.57–10.80, p = 0.006). Definitive antimicrobial therapy with intravenous or highly bioavailable oral agents was associated with reduced risk of treatment failure (HR 0.33, 95% CI: 0.14–0.73, p = 0.006).

Conclusions

The current results support common clinical practice of 2 weeks of antimicrobial therapy for uncomplicated Gram-negative BSI.

     

Identifying Subpopulations with Distinct Response to Treatment Using Plasma Biomarkers in Acute Heart Failure: Results from the PROTECT Trial

Background

Over the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.

Methods

We studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.

Results

In the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82–1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1α, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1α, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40–0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68–18.13, p = 0.005; treatment by score interaction p < 0.001). Internal validation estimated similar hazard ratio estimates (0 points: HR 5.56, 95% CI 5.27–7–5.87; 1 point: HR 1.31, 95% CI 1.25–1.33; 2 points: HR 0.75, 95% CI 0.74–0.76; 3 points: HR 1.13, 95% CI 1.11–1.15; 4 points, HR 0.61, 95% CI 0.61–0.62) compared to the original data.

Conclusion

Biomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.

     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.