Cerebrovascular autoregulation monitoring and patient‐centred outcomes after cardiac surgery: a systematic review

Background

Impaired cerebrovascular autoregulation (CVAR) is observed in up to 20% of cardiac surgical patients. This systematic review aims to evaluate the association between impaired CVAR, measured by current monitoring techniques, and patient‐centred outcomes in adults following cardiac surgery.

Methods

MEDLINE, EMBASE, PubMed, MEDLINE In‐Process and Cochrane Library were systematically searched through 8 December 2017. Studies were included if they assessed associations between CVAR and patient‐centred outcomes in the adult cardiac surgical population. The primary outcome of this systematic review was mortality. Secondary outcomes were stroke, delirium and acute kidney injury. Risk of bias was systematically assessed, and the GRADE methodology was used to evaluate the quality of evidence across outcomes.

Results

Eleven observational studies and no randomised controlled trials met the inclusion criteria. Due to methodological heterogeneity, meta‐analysis was not possible. There was a high risk of bias within individual studies and low quality of evidence across outcomes. Of the included studies, one assessed mortality, five assessed stroke, four assessed delirium, and three assessed acute kidney injury. No reliable conclusions can be drawn from the one study assessing mortality. Interpretation of studies investigating CVAR and stroke, delirium and acute kidney injury was complicated by the lack of standardisation of monitoring techniques as well as varying definitions of impaired CVAR.

Conclusions

There is a paucity of high quality evidence for CVAR monitoring and its associations with outcome measures in post‐cardiac surgical patients, highlighting the need for future studies.

     

Corticosteroids and risk of gastrointestinal bleeding in critically ill adults: Protocol for a systematic review

Background

Corticosteroids are frequently prescribed to critically ill patients. However, their use may increase the risk of gastrointestinal (GI) bleeding, which is associated with morbidity and mortality. Accordingly, we aim to assess whether continued administration of corticosteroids for >24 hours increases the rate of GI bleeding in adult critically ill patients compared to placebo or no treatment.

Methods/Design

We will conduct a systematic review of randomized clinical trials with meta‐analysis and trial sequential analysis. The participants will be adult (as defined in the included trials) critically ill patients. The intervention will be any corticosteroid administered systematically for >24 hours and the comparator will be placebo or no treatment. The primary outcome will be rate of clinically important GI bleeding. We will systematically search EMBASE, MEDLINE, Medline In‐Process, Cochrane Library, Epistemonikos and trial registries for relevant literature, as well as perform a hand search. We will follow the recommendations by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) statement. The risk of systematic errors (bias) and random errors will be assessed and the overall quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Discussion

The risk of GI bleeding in adult critically ill patients treated with corticosteroids is unknown. Hence, there is need for a robust systematic review to assess this risk and provide clinicians with a clearer understanding of the strength and limitations of existing data.

     

Stress ulcer prophylaxis in adult intensive care unit patients – a protocol for a systematic review

Background

In the intensive care unit (ICU), stress ulcer prophylaxis with proton pump inhibitors or histamine‐2‐receptor antagonists is standard of care although gastrointestinal bleeding remains uncommon. It remains unknown whether its use is associated with benefits or harms and the quality of evidence supporting the use of stress ulcer prophylaxis has been questioned. Accordingly, the objective of this systematic review was to critically assess the evidence from randomized clinical trials on the benefits and harms of stress ulcer prophylaxis vs. placebo or no prophylaxis in adult ICU patients.

Methods

We will systematically search for randomized clinical trials in major international databases. Two authors will independently screen and select trials for inclusion, extract data and assess the methodological quality using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will perform conventional meta‐analyses using Review Manager, and STATA 15, and we will assess the risk of random errors using Trial Sequential Analysis. Also, we will assess and report the overall quality of evidence for all outcomes according to GRADE.

Discussion

The evidence on the benefits and harms of stress ulcer prophylaxis in adult ICU patients is unclear and an updated systematic review is warranted as new trials have been published. To control risks of systematic and random errors, we will use Cochrane and GRADE methodology and Trial Sequential Analysis. Our ambition with this systematic review is to provide updated, reliable and precise data to better inform decision makers on the use of stress ulcer prophylaxis in adult ICU patients.

     

Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta‐analysis

Background

Postoperative cognitive complications are associated with substantial morbidity and mortality. Ketamine has been suggested to have neuroprotective effects in various settings. This systematic review evaluates the effects of intraoperative ketamine administration on postoperative delirium and postoperative cognitive dysfunction (POCD).

Methods

Medline, Embase and Central were searched to 4 March 2018 without date or language restrictions. We considered randomised controlled trials (RCTs) comparing intraoperative ketamine administration versus no intervention in adults undergoing surgery under general anaesthesia. Primary outcomes were postoperative delirium and POCD. Non‐cognitive adverse events, mortality and length of stay were considered as secondary outcomes. Data were independently extracted. The quality of the evidence (GRADE approach) was assessed following recommendations from the Cochrane collaboration. Risk ratios were calculated for binary outcomes, mean differences for continuous outcomes. We planned to explore the effects of age, specific anaesthesia regimen, depth of anaesthesia and intraoperative haemodynamic events through subgroup analyses.

Results

Six RCTs were included. The incidence of postoperative delirium did not differ between groups (4 trials, 557 patients, RR 0.83, 95% CI [0.25, 2.80]), but patients receiving ketamine seemed at lower risk of POCD (3 trials, 163 patients, RR 0.34, 95% CI [0.15, 0.73]). However, both analyses presented limitations. Therefore, the quality of the evidence (GRADE) was deemed low (postoperative delirium) and very low (POCD).

Conclusion

The effect of ketamine on postoperative delirium remains unclear but its administration may offer some protection towards POCD. Large, well‐designed randomised trials are urgently needed to further clarify the efficacy of ketamine on neurocognitive outcomes.

     

Perioperative hyperoxia and post‐operative cardiac complications in adults undergoing non‐cardiac surgery: Systematic review protocol

Background

Oxygen therapy is used liberally for all patients undergoing anaesthesia. Recent studies have raised concerns that it may not be without complications when arterial oxygen concentrations reach supranormal concentrations (hyperoxia). Studies of oxygen therapy have raised concerns that the risk of myocardial injury and infarction is elevated in patients with hyperoxia due to vasoconstriction and formation of reactive oxygen species. Due to lack of symptoms or silent ischaemia, post‐operative myocardial injury may be missed clinically. In some studies, perioperative hyperoxia has been linked to increased long‐term mortality, but cardiac complications are sparsely evaluated. The aim of this review is to summarize current evidence to assess the risk and benefits of perioperative hyperoxia on post‐operative cardiac complications.

Methods

This systematic review will include meta‐analyses and Trial Sequential Analyses. We will include randomized clinical trials with patients undergoing non‐cardiac surgery if the allocation separates patients into a target of either higher (above 0.60) or lower (below 0.40) inspired oxygen fraction. To minimize the risk of systematic error, we will assess the risk of bias of the included trials using the Cochrane Risk of Bias Tool. The overall quality of evidence for each outcome will be assessed with the Grading of Recommendation, Assessment, Development and Evaluation (GRADE).

Discussion

This systematic review will provide data on a severe, albeit rare, potential risk of oxygen therapy. We will do a trial sequential analysis to assess the robustness of results as well as help estimate the required patient size for future clinical trials.

     

Effect of requiring a general practitioner at scenes of serious injury: A systematic review

Background

In Norway, each municipality is responsible for providing first line emergency healthcare, and it is mandatory to have a primary care physician/general practitioner on call continuously. This mandate ensures that a physician can assist patients and ambulance personnel at the site of severe injuries or illnesses. The compulsory presence of the general practitioner at the scene could affect different parts of patient treatment, and it might save resources by obviating resources from secondary healthcare, like pre‐hospital anaesthesiologists and other specialized resources. This systematic review aimed to examine how survival, time spent at the scene, the choice of transport destination, assessment of urgency, the number of admissions, and the number of cancellations of specialized pre‐hospital resources were affected by the presence of a general practitioner at the scene of a suspected severe injury.

Methods

We searched for published and planned systematic reviews and primary studies in the Cochrane Library, Medline, Embase, OpenGrey, GreyLit and trial registries. The search was completed in December 2017. Two individuals independently screened the references and assessed the eligibility of all potentially relevant studies.

Results

The search for systematic reviews and primary studies identified 5981 articles. However, no studies met the pre‐defined inclusion criteria.

Conclusion

No studies met our inclusion criteria; consequently, it remains uncertain how the presence of a general practitioner at the injury scene might affect the selected outcomes.

     

Oxygen supplementation for critically ill patients—A protocol for a systematic review

Background

In critically ill patients, hypoxaemia is a common clinical manifestation of inadequate gas exchange in the lungs. Supplemental oxygen is therefore given to all critically ill patients. This can result in hyperoxaemia, and some observational studies have identified harms with hyperoxia. The objective of this systematic review is to critically assess the evidence of randomised clinical trials on the effects of higher versus lower inspiratory oxygen fractions or targets of arterial oxygenation in critically ill adult patients.

Methods

We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and Trial Sequential Analysis. To assess the quality of the evidence, we will create a ‘Summary of Findings’ table containing our primary and secondary outcomes using the GRADE assessment.

Discussion

Supplemental oxygen administration is widely recommended in international guidelines despite lack of robust evidence of its effectiveness. To our knowledge, no systematic review of randomised clinical trials has investigated the effects of oxygen supplementation in critically ill patients. This systematic review will provide reliable evidence to better inform future trialists and decision‐makers on clinical practice on supplemental oxygen administration in critically ill patients.

     

The efficacy and safety of cold‐induced lipolysis in the treatment of pseudogynecomastia

Background

The treatment options for pseudogynecomastia have been limited. Cold‐induced lipolysis provides a noninvasive, localized subcutaneous adipocyte destruction by inducing adipocyte apoptosis.

Objective

This study has been designed to evaluate the efficacy of cold‐induced lipolysis as a treatment modality for pseudogynecomastia.

Methods

In this 28‐week prospective trial, a total of 12 male pseudogynecomastia patients (Korean) were treated twice with cold‐induced lipolysis. Efficacy was determined by chest circumference, ultrasonographic measurement of fat thickness, Simon's Gynecomastia class (SGC), photographic assessment, and the patient's satisfaction (baseline, weeks 4, 8, 16, and 28). Using a questionnaire, safety was evaluated at each visit.

Results

For 10 subjects that completed the trial, chest circumference and fat thickness significantly improved by week 8. This same improvement was gradually noticed through week 28. The patients SGC scores continuously decreased after two sessions. Photographic assessment showed an improvement until week 28. The result of the patient's satisfaction score was also meaningful. While there were no adverse events observed, transient pain and bruising at the treatment site were noticed.

Limitations

We recruited a limited number of participants. Also, we could not exclude there might be other individual factors in association with the patients pseudogynecomastia.

Conclusion

Cold‐induced lipolysis is a safe, effective therapeutic option in the treatment of pseudogynecomastia. Lasers Surg. Med. 48:584–589, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals Inc.

     

Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): systematic reviews and meta‐analyses of longitudinal studies of HPV acquisition and clearance by HIV status,and of HIV acquisition by HPV status

Introduction

Observational studies suggest HIV and human papillomavirus (HPV) infections may have multiple interactions. We reviewed the strength of the evidence for the influence of HIV on HPV acquisition and clearance, and the influence of HPV on HIV acquisition.

Methods

We performed meta‐analytic systematic reviews of longitudinal studies of HPV incidence and clearance rate by HIV status (review 1) and of HIV incidence by HPV status (review 2). We pooled relative risk (RR) estimates across studies using random‐effect models. I² statistics and subgroup analyses were used to quantify heterogeneity across estimates and explore the influence of participant and study characteristics including study quality. Publication bias was examined quantitatively with funnel plots and subgroup analysis, as well as qualitatively.

Results and Discussion

In review 1, 37 publications (25 independent studies) were included in the meta‐analysis. HPV incidence (pooled RR = 1.55, 95% CI: 1.29 to 1.88; heterosexual males: pooled RR = 1.95, 95% CI: 1.62, 2.34; females: pooled RR = 1.63, 95% CI: 1.26 to 2.11; men who have sex with men: pooled RR = 1.36, 95% CI: 1.01 to 1.82) and high‐risk HPV incidence (pooled RR = 2.20, 95% CI: 1.90 to 2.54) was approximately doubled among people living with HIV (PLHIV) whereas HPV clearance rate (pooled RR = 0.53, 95% CI: 0.42 to 0.67) was approximately halved. In review 2, 14 publications (11 independent studies) were included in the meta‐analysis. HIV incidence was almost doubled (pooled RR = 1.91, 95% CI 1.38 to 2.65) in the presence of prevalent HPV infection. There was more evidence of publication bias in review 2, and somewhat greater risk of confounding in studies included in review 1. There was some evidence that adjustment for key confounders strengthened the associations for review 2. Misclassification bias by HIV/HPV exposure status could also have biased estimates toward the null.

Conclusions

These results provide evidence for synergistic HIV and HPV interactions of clinical and public health relevance. HPV vaccination may directly benefit PLHIV, and help control both HPV and HIV at the population level in high prevalence settings. Our estimates of association are useful for mathematical modelling. Although observational studies can never perfectly control for residual confounding, the evidence presented here lends further support for the presence of biological interactions between HIV and HPV that have a strong plausibility.

     

Purely off‐clamp robotic partial nephrectomy: Preliminary 3‐year oncological and functional outcomes

Objectives

To describe our surgical technique and to report perioperative, 3‐year oncological and functional outcomes of a single‐center series of purely off‐clamp robotic partial nephrectomy.

Methods

A prospective renal cancer institutional database was queried, and data of consecutive patients treated with purely off‐clamp robotic partial nephrectomy between 2010 and 2015 in a high‐volume center were collected. Perioperative complications, and 3‐year oncological and functional outcomes were assessed. Univariable and multivariable analyses were carried out to identify independent predictors of renal function deterioration.

Results

Out of 308 patients treated, 41 (13.3%) experienced perioperative complications, 2.9% of which were Clavien grade ≥3. The 3‐year local recurrence‐free survival and renal cell carcinoma‐specific survival rates were 99.5% and 97.9%, respectively. No patient with preoperative chronic kidney disease stage ≤3B developed severe renal function deterioration (chronic kidney disease stage 4) at 1‐year follow up. At multivariable analysis, preoperative estimated glomerular filtration rate (P = 0.005) was the only independent predictor of a new‐onset chronic kidney disease stage ≥3 in patients with preoperative chronic kidney disease stages 1 or 2.

Conclusions

Off‐clamp robotic partial nephrectomy is a safe surgical approach in tertiary referral centers, with adequate oncological outcomes and negligible impact on renal function.

     

Accuracy of administrative coding data in colorectal cancer resections and short‐term outcomes

Background

Administrative data are routinely captured for each hospital admission and may serve as an alternative source for populating databases. This study aims to determine the accuracy of administrative data to provide tumour characteristics and short‐term post‐operative outcomes, after a colorectal cancer (CRC) resection, compared with clinical data.

Methods

A retrospective study of all CRC resections at a single hospital from 1 January 2008 to 31 December 2013 was conducted. Local administrative data were coded as per ICD‐10‐AM (International Classification of Diseases, Tenth Revision, Australian Modification) and Australian Classification of Health Interventions. Clinical data for all patients were extracted from the medical charts and compared with administrative data. Code combinations and algorithms were used to improve the accuracy of administrative data.

Results

A total of 436 patients were identified. The accuracy of algorithms combining tumour location and type of operation for right colon, left colon and rectum were 93, 89 and 88%, respectively. The accuracy of histological type was 89%, lymph node status 92% and metastasis status 88%. The accuracy of return to theatre and in‐hospital mortality was 100%.

Conclusion

Administrative data can provide reliable information on tumour details and short‐term post‐operative outcomes. The potential for administrative data to validate data captured in registries and be used independently for audit and research should be further explored.

     

Delay in Diagnosis and Its Effect on Clinical Outcome in High‐grade Sarcoma of Bone: A Referral Oncological Centre Study

Objective

To investigate delay in diagnosis by both patients and doctors, and to evaluate its effect on outcomes of high‐grade sarcoma of bone in a single‐referral oncological center.

Methods

Fifty‐four patients with osteosarcoma, 29 with Ewing sarcoma and 19 with chondrosarcoma were enrolled in this retrospective study. Delay in diagnosis was defined as the period between initial clinical symptoms and histopathological diagnosis at our center. The delays were categorized as patient‐ or doctor‐related. Short total delays were defined as <4 months; prolonged delays >4 months were assumed to have prognostic relevance.

Results

Total delay in diagnosis was 688.0 days in patients with chondrosarcoma, which is significantly longer than the 163.3 days for osteosarcoma (P < 0.01) and 160.2 days for Ewing sarcoma (P < 0.01). Most doctor‐related delays were at the pre‐hospital stage, occurring at the general practitioner (GP)'s office. However, prolonged total delays (≥4 months) did not result in lower survival rates. Five‐year‐overall survival rates were 67.0% for osteosarcoma, 49.0% for Ewing sarcoma and 60.9% for chondrosarcoma. Survival was significantly lower for patients with metastatic disease for all three types of sarcoma.

Conclusion

Prolonged delay in diagnosis does not result in lower survival. Metastatic disease has a pronounced effect on survival. Aggressive tumor behavior results in shorter delays. Minimizing GP‐related delays could be achieved by adopting a lower threshold for obtaining plain radiographs at the pre‐hospital stage.

     

A five‐CpG DNA methylation score to predict metastatic‐lethal outcomes in men treated with radical prostatectomy for localized prostate cancer

Background

Prognostic biomarkers for localized prostate cancer (PCa) could improve personalized medicine. Our group previously identified a panel of differentially methylated CpGs in primary tumor tissue that predict disease aggressiveness, and here we further validate these biomarkers.

Methods

Pyrosequencing was used to assess CpG methylation of eight biomarkers previously identified using the HumanMethylation450 array; CpGs with strongly correlated (r >0.70) results were considered technically validated. Logistic regression incorporating the validated CpGs and Gleason sum was used to define and lock a final model to stratify men with metastatic‐lethal versus non‐recurrent PCa in a training dataset. Coefficients from the final model were then used to construct a DNA methylation score, which was evaluated by logistic regression and Receiver Operating Characteristic (ROC) curve analyses in an independent testing dataset.

Results

Five CpGs were technically validated and all were retained (P < 0.05) in the final model. The 5‐CpG and Gleason sum coefficients were used to calculate a methylation score, which was higher in men with metastatic‐lethal progression (P = 6.8 × 10^?6) in the testing dataset. For each unit increase in the score there was a four‐fold increase in risk of metastatic‐lethal events (odds ratio, OR = 4.0, 95%CI = 1.8–14.3). At 95% specificity, sensitivity was 74% for the score compared to 53% for Gleason sum alone. The score demonstrated better prediction performance (AUC = 0.91; pAUC = 0.037) compared to Gleason sum alone (AUC = 0.87; pAUC = 0.025).

Conclusions

The DNA methylation score improved upon Gleason sum for predicting metastatic‐lethal progression and holds promise for risk stratification of men with aggressive tumors. This prognostic score warrants further evaluation as a tool for improving patient outcomes.

     

Prostate‐specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer

Objective

To clarify the impact of prostate‐specific antigen screening on surgical outcomes of prostate cancer.

Methods

Patients who underwent radical prostatectomy were divided into two groups according to prostate‐specific antigen testing opportunity (group 1, prostate‐specific antigen screening; group 2, non‐prostate‐specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank‐sum and χ²‐tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence‐free survival.

Results

In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate‐specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5‐year biochemical recurrence‐free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate‐specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate‐specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate‐specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study.

Conclusions

Detection by screening results in favorable outcomes after surgery. Prostate‐specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer.

     

Evaluation of Quality of Life Using EORTC QLQ‐BM22 in Patients with Bone Metastases after Treatment with Magnetic Resonance Guided Focused Ultrasound

Objective

To reveal the alterations in quality of life (QOL) in bone metastases patients after magnetic resonance guided focused ultrasound (MRgFUS).

Methods

This retrospective study enrolled 26 patients diagnosed with bone metastases. Patients had various primary malignant tumors and tumor lesions in different locations. All patients received MRgFUS for bone metastasis. Each focal spot sonication pulse that was applied to create energy deposition lasted 20 s and was performed at a frequency of 1.05 MHz. The visual analog scale (VAS) was used to measure pain level and the EORTC QLQ‐BM22 was applied to evaluate QOL for 12 months. The lower the QLQ‐BM22 score, the better the QOL of patients.

Results

The painful site subscale of the EORTC QLQ‐BM22 was observed without significant change. Significant reductions in the functional subscales were observed after therapy compared with the baseline. The functional interference was reduced significantly during the first 12 months. From the 2‐month time point onwards, the pain characteristics subscale also decreased significantly. VAS scores had decreased by 40.8% 1 month after the operation and had decreased 10.9% compared with VAS scores preoperation. Scores for pain characteristics decreased by 28.8% after the operation and the scores were still down by 10.8% 1 year after the treatment. VAS scores indicated a significant reduction in pain over the course of the research until the 12‐month time point follow‐up compared with the baseline.

Conclusion

MRgFUS therapy improved the QOL of patients with bone metastasis by relieving bone pain.

     

The Relationship Between Metformin and Serum Prostate‐Specific Antigen Levels

BACKGROUND

Metformin is the first‐line oral antihyperglycemic of choice for individuals with type 2 diabetes. Recent evidence supports a role for metformin in prostate cancer chemoprotection. However, whether metformin indeed influences prostate biology is unknown. We aimed to study the association between metformin and serum prostate‐specific antigen (PSA) levels—the primary prostate cancer biomarker.

METHODS

We conducted a cross‐sectional study of 326 prostate cancer‐free men with type 2 diabetes were recruited between 2004 and 2013 at St. Michael's Hospital. Men were excluded if they had a PSA ≥10‐ng/ml, or used >2,550‐mg/d metformin or supplemental androgens. Multivariate linear regressions quantified the association between metformin dose and log‐PSA. Secondary analyses quantified the association between other antihyperglycemics (sulfonylureas, thiazolidinediones) and PSA; sensitivity analyses tested covariate interactions.

RESULTS

Median PSA was 0.9‐ng/ml (IQR: 0.5–1.6‐ng/ml). Metformin dose associated positively with BMI, HbA1c, diabetes duration, and number of statin, acetylsalicylic acid, diuretic users, and number of antihyperglycemics used, and negatively with LDL‐C. In multivariate models, PSA changed by ?8% (95%CI: ?13 to ?2%, P = 0.011) per 500‐mg/d increase in metformin. Men with diabetes for ≥6 years (n = 163) saw a greater difference in PSA per 500‐mg/d metformin (?12% [95% CI: ?19 to ?4%, P = 0.002], P‐interaction = 0.018). Serum PSA did not relate with sulfonylureas, thiazolidinediones, or total number of antihyperglycemic agents used. Our findings are limited by the cross‐sectional design of this study.

CONCLUSIONS

Metformin dose‐dependently inversely associated with serum PSA, independent of other antihyperglycemic medications. Whether metformin confers a dose‐dependent benefit on prostate tumorigenesis and progression warrants investigation. Prostate 76:1445–1453, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.

     

Development of a new patient‐reported outcome (PRO) measure on the Impact of Nighttime Urination (INTU) in patients with nocturia—Psychometric validation

Aims

To psychometrically evaluate the Impact of Nighttime Urination (INTU) questionnaire, a new patient‐reported outcome measure developed to assess the impact of nocturia on health and functioning in a multicenter, behavioral modification (fluid restriction) study.

Methods

Participants aged 50‐95 years with at least two voiding episodes/night for ≥6 months completed voiding diaries and the INTU on 3 consecutive days during weeks 1 and 2 (same day recall) and completed the Pittsburgh Sleep Quality Index (PSQI) and Nocturia Quality of Life Questionnaire (N‐QOL) at baseline and days 8 and 15. Psychometric evaluations of the INTU were conducted.

Results

Rasch analysis showed the INTU to be a unidimensional construct, with most items located on the severe end of the symptom severity continuum. In addition to an Overall Impact Score (10 items), exploratory factor analysis affirmed by confirmatory factor analysis identified two domains: Daytime (six items) and Nighttime (four items) Impact Scores (comparative fit index = 0.968; root mean square error of approximation = 0.08). Concurrent validity met prespecified hypotheses, indicating similarity of concepts with the PSQI (correlation [r] = 0.627) and N‐QOL (r = ?0.784) total scores. The INTU differentiated among patients with different nocturic episode frequencies (P < 0.05 for all three summary scores). Statistically significant decreases were observed in mean Overall and Nighttime Impact Scores at week 2 versus week 1 in responders, indicating that the instrument can detect changes in response to symptom improvements.

Conclusions

The INTU questionnaire demonstrated robust measurement properties and is a suitable tool for assessing the patient‐reported impact of nocturia on health and functioning.

     

Partial nephrectomy for small children: Robot‐assisted versus open surgery

Objectives

To compare the outcomes of robot‐assisted heminephrectomy for duplex kidney in children with those of open heminephrectomy.

Methods

The present retrospective multicentric analysis reviewed the records of robot‐assisted versus open heminephrectomy carried out for duplex kidney in children from 2007 to 2014. Demographic data, weight, surgical time, hospital stay, complications and outcome were recorded. Follow up was based on a clinical review, renal sonography and dimercaptosuccinic acid renal scintigraphy.

Results

A total of 15 patients underwent robot‐assisted heminephrectomy, and 13 patients underwent retroperitoneal heminephrectomy by open approach. All patients weighed <15 kg. The mean age at the time of surgery was 20.2 months (range 7–39 months) in the robotic group, and 18.4 months (range 6–41 months) in the open group. The mean hospital stay was statistically longer for the open surgery group (6.3 days, range 5–8 days vs 3.4 days, range 1–7 days; P < 0.001). Regarding postoperative pain control, total morphine equivalent intake was statistically greater for the open group (0.52 mg/kg/day vs 1.08 mg/kg/day; P < 0.001). No patient lost the remaining healthy moiety. There was no significant difference in terms of operating time, complication rate or renal outcomes.

Conclusions

Robot‐assisted heminephrectomy in small children seems to offer comparable renal outcomes with those of its standard open surgery counterpart. Specific technical adjustments are necessary, which typically increase the set‐up time.

     

A two‐drug combination simulation study for metastatic castrate resistant prostate cancer

Background

Prostate cancer often evolves resistance to androgen deprivation therapy leading to a lethal metastatic castrate‐resistant form. Besides androgen independence, subpopulations of the tumor are genetically heterogeneous. With the advent of tumor genome sequencing we asked which has the greater influence on reducing tumor size: genetic background, heterogeneity, or drug potency?

Methods

A previously developed theoretical evolutionary dynamics model of stochastic branching processes is applied to compute the probability of tumor eradication with two targeted drugs. Publicly available data sets were surveyed to parameterize the model.

Results

Our calculations reveal that the greatest influence on successful treatment is the genetic background including the number of mutations overcoming resistance. Another important criteria is the tumor size at which it is still possible to achieve tumor eradication, for example, 2‐4 cm large tumors have at best a 10% probability to be eradicated when 50 mutations can confer resistance to each drug.

Conclusion

Overall, this study finds that genetic background and tumor heterogeneity are more important than drug potency in treating mCRPC. It also points toward identifying metastatic sites early using biochemical assays and/or dPET.

     

Oral administration of cernitin pollen extract (Cernilton®) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study

Objectives

To assess the effect of cernitin pollen extract on serum prostate‐specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure.

Methods

A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate‐specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate‐specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer.

Results

The mean change in serum prostate‐specific antigen and rate of change after administration of cernitin pollen extract in all patients were ?0.6 ± 1.4 ng/mL and ?7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate‐specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively).

Conclusions

The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate‐specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.