Seminal papers in urology: two-year outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for refractory urgency urinary incontinence: a Randomized Trial.

In this critical review, we explore the study design, strengths and limitations of the paper: "Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial." The paper reports 24 month follow-up data of the landmark ROSETTA trial. This multi-centre, open-labelled parallel randomised trial allocated females 1:1 to receive Sacral Neuromodulation (SNM) or OnabotulinumtoxinA(BTX) 200 units (U). The primary outcome was change in mean daily urinary urgency incontinence episodes (UUIE) over 24 months. The study did not demonstrate a difference between treatments (-3.88 vs. -3.50 episodes per day), however women treated with BTX were more satisfied; but reported higher rates of UTI. The two treatments provide comparable third-line treatment options for patients with refractory urgency urinary incontinence.

Responsiveness and construct validity of EPIC-26, AQoL-6D and SF-6D following treatment in prostate cancer.

PURPOSE: To assess construct validity and responsiveness of the Expanded Prostate Cancer Index Composite Instrument (EPIC-26) relative to the Short-Form Six-Dimension (SF-6D) and Assessment of Quality of Life 6-Dimension (AQoL-6D) in patients following treatment for prostate cancer. METHODS: Retrospective prostate cancer registry data were used. The SF-6D, AQoL-6D, and EPIC-26 were collected at baseline and one year post treatment. Analyses were based on Spearman's correlation coefficient, Bland-Altman plots and intra-class correlation coefficient, Kruskal Wallis, and Effect Size and the Standardised Response Mean for responsiveness. RESULTS: The study sample was comprised of 1915 patients. Complete case analysis of 3,697 observations showed moderate evidence of convergent validity between EPIC-26 vitality/hormonal domain and AQoL-6D (r = 0.45 and 0.54) and SF-6D (r = 0.52 and 0.56) at both timepoints. Vitality/hormonal domain also showed moderate convergent validity with coping domain of AQoL-6D (r = 0.45 and 0.54) and with role (r = 0.41 and 0.49) and social function (r = 0.47 and 0.50) domains of SF-6D at both timepoints, and with independent living (r = 0.40) and mental health (r = 0.43) of AQoL-6D at one year. EPIC-26 sexual domain had moderate convergent validity with relationship domain (r = 0.42 and 0.41) of AQoL-6D at both timepoints. Both AQoL-6D and SF-6D did not discriminate between age groups and tumour stage at both timepoints but AQoL-6D discriminated between outcomes for different treatments at one year. All EPIC-26 domains discriminated between age groups and treatment at both timepoints. The EPIC-26 was more responsive than AQoL-6D and SF-6D between baseline and one year following treatment. CONCLUSIONS: AQoL-6D can be used in combination with EPIC-26 in place of SF-12. Although EPIC-26 is not utility based, its popularity amongst clinicians and ability to discriminate between disease-specific characteristics and post-treatment outcomes in clinical trials makes it a candidate for use within cost-effectiveness analyses. The generic measure provides a holistic assessment of quality of life and is suitable for generating quality adjusted life years (QALYs).

The Effect of Dietary Nitrate on the Contractile Properties of Human Skeletal Muscle: A Systematic Review and Meta-Analysis.

The propose of this study was to systematically review the current literature and meta-analyse the effects of dietary nitrate (NO3-) supplementation on the contractile properties of skeletal muscle. A literature search of three databases was conducted in June 2021, with 19 studies meeting the inclusion criteria. Studies were included if a placebo versus dietary NO3--only supplementation protocol was used in healthy human, assessed muscle contraction or activities that was < 3 minutes in duration and focused on the lower-body. For the meta-analysis, a pooled standardised mean difference (SMD) was determined for maximum voluntary contraction (MVC) (n = 11), cycling, running and inertial load squad peak power output (PPO) (n = 8), mean power output (MPO) (n = 6) and time to PPO (n = 4). NO3- supplementation demonstrated a small improvement in PPO (SMD = 0.25, P = 0.030) and MPO (SMD = 0.28, P = 0.030) when compared to the placebo. NO3- also resulted in an enhanced time to PPO (SMD = -0.78, P < 0.001). There was no clear effect of NO3- on isometric MVC (SMD = 0.03, P = 0.758). This review reports that NO3- supplementation may have potential to enhance PPO, MPO and time to PPO during dynamic exercise, which may transfer to brief explosive actions commonly observed in sporting activities. Due to the variability in studies, we encourage researchers to use this work to explore areas where evidence in lacking and standardize the study design and procedures.Key teaching pointsFindings from this meta-analysis highlight the potential positive ergogenic effect of dietary NO3-supplementation on PPO, MPO and time to PPO during short duration (<10 s) dynamic exercise.NO3- supplementation might be considered as an ergogenic aid when executing power-based actions (e.g., 100 m sprinter or weightlifter).This review highlights that further research is required to address some of the contrasting findings presented here using a standardised procedure to allow for improved synthesis.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center.

Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.

Predicting post-radiation genitourinary hospital admissions in patients with localised prostate cancer.

PURPOSE: The risk of treatment-related toxicity is important for patients with localised prostate cancer to consider when deciding between treatment options. We developed a model to predict hospitalisation for radiation-induced genitourinary toxicity based on patient characteristics. METHODS: The prospective South Australian Prostate Cancer Clinical Outcomes registry was used to identify men with localised prostate cancer who underwent curative intent external beam radiotherapy (EBRT) between 1998 and 2019. Multivariable Cox proportional regression was performed. Model discrimination, calibration, internal validation and utility were assessed using C-statistics and area under ROC, calibration plots, bootstrapping, and decision curve analysis, respectively. RESULTS: There were 3,243 patients treated with EBRT included, of which 644 (20%) patients had a treated-related admission. In multivariable analysis, diabetes (HR 1.35, 95% CI 1.13-1.60, p < 0.001), smoking (HR 1.78, 95% CI 1.40-2.12, p < 0.001), and bladder outlet obstruction (BOO) without transurethral resection of prostate (TURP) (HR 7.49, 95% CI 6.18-9.08 p < 0.001) followed by BOO with TURP (HR 4.96, 95% CI 4.10-5.99 p < 0.001) were strong independent predictors of hospitalisation (censor-adjusted c-statistic = 0.80). The model was well-calibrated (AUC = 0.76). The global proportional hazards were met. In internal validation through bootstrapping, the model was reasonably discriminate at five (AUC 0.75) years after radiotherapy. CONCLUSIONS: This is the first study to develop a predictive model for genitourinary toxicity requiring hospitalisation amongst men with prostate cancer treated with EBRT. Patients with localised prostate cancer and concurrent BOO may benefit from TURP before EBRT.

Can a practice pharmacist improve prescribing safety and reduce costs in polypharmacy patients? A pilot study of an intervention in an Irish general practice setting.

OBJECTIVES: This study aimed to develop and assess the feasibility and cost impact of an intervention involving a practice pharmacist embedded in general practice to improve prescribing safety, deprescribe where appropriate and reduce costs. SETTING: Four-doctor suburban general practice. PARTICIPANTS: Inclusion criteria: patients receiving 10+ repeat drugs per month. EXCLUSION CRITERIA: deceased, <18 years of age, nursing home resident, no longer attending, late-stage life-limiting condition, unsuitable on clinical/capacity grounds. 137 patients were eligible. 78 were recruited as participants, all of whom completed the study. INTERVENTION: Pharmacist conducting holistic medication reviews in the study group over a 6-month period. PRIMARY OUTCOME MEASURES: Anonymised medication changes, cost, biochemical monitoring and clinical measurements data were collected. Cost analysis of having a pharmacist as part of the general practice team was calculated. RESULTS: In total, 198 potentially inappropriate prescriptions (PIPs), and 163 opportunities for deprescribing were identified; 127 PIPs (64.1%) were actioned; 104 deprescribing opportunities were actioned (63.8%). The pharmacist identified 101 instances in which further investigations were warranted prior to prescription issue, of which 80 were actioned (79.2%). It was calculated that monthly savings of €1252 were made as a result of deprescribing. CONCLUSIONS: This study has shown that the integration of pharmacists within general practice in Ireland is feasible and is an effective means of improving prescribing safety and implementing deprescribing through medication reviews. The combination of safety and cost concerns support taking a holistic approach to deprescribing with the patient. This study highlights the ease with which a pharmacist could integrate into the general practice setting in Ireland and points to how this could be sustainably funded.

Effect of nitrate supplementation on skeletal muscle motor unit activity during isometric blood flow restriction exercise.

BACKGROUND: Nitrate (NO3-) supplementation has been reported to lower motor unit (MU) firing rate (MUFR) during dynamic resistance exercise; however, its impact on MU activity during isometric and ischemic exercise is unknown. PURPOSE: To assess the effect of NO3- supplementation on knee extensor MU activities during brief isometric contractions and a 3 min sustained contraction with blood flow restriction (BFR). METHODS: Sixteen healthy active young adults (six females) completed two trials in a randomized, double-blind, crossover design. Trials were preceded by 5 days of either NO3- (NIT) or placebo (PLA) supplementation. Intramuscular electromyography was used to determine the M. vastus lateralis MU potential (MUP) size, MUFR and near fibre (NF) jiggle (a measure of neuromuscular stability) during brief (20 s) isometric contractions at 25% maximal strength and throughout a 3 min sustained BFR isometric contraction. RESULTS: Plasma nitrite (NO2-) concentration was elevated after NIT compared to PLA (475 ± 93 vs. 198 ± 46 nmol L-1, p < 0.001). While changes in MUP area, NF jiggle and MUFR were similar between NIT and PLA trials (all p > 0.05), MUP duration was shorter with NIT compared to PLA during brief isometric contractions and the sustained ischemic contraction (p < 0.01). In addition, mean MUP duration, MUP area and NF jiggle increased, and MUFR decreased over the 3 min sustained BFR isometric contraction for both conditions (all p < 0.05). CONCLUSIONS: These findings provide insight into the effect of NO3- supplementation on MUP properties and reveal faster MUP duration after short-term NO3- supplementation which may have positive implications for skeletal muscle contractile performance.

Evaluation of Hypofractionated Radiation Therapy Use and Patient-Reported Outcomes in Men With Nonmetastatic Prostate Cancer in Australia and New Zealand.

Importance: Randomized clinical trials in prostate cancer have reported noninferior outcomes for hypofractionated radiation therapy (HRT) compared with conventional RT (CRT); however, uptake of HRT across jurisdictions is variable. Objective: To evaluate the use of HRT vs CRT in men with nonmetastatic prostate cancer and compare patient-reported outcomes (PROs) at a population level. Design, Setting, and Participants: Registry-based cohort study from the Australian and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Participants were men with nonmetastatic prostate cancer treated with primary RT (excluding brachytherapy) from January 2016 to December 2019. Data were analyzed in March 2021. Exposures: HRT defined as 2.5 to 3.3 Gy and CRT defined as 1.7 to 2.3 Gy per fraction. Main Outcomes and Measures: Temporal trends and institutional, clinicopathological, and sociodemographic factors associated with use of HRT were analyzed. PROs were assessed 12 months following RT using the Expanded Prostate Cancer Index Composite (EPIC)-26 Short Form questionnaire. Differences in PROs were analyzed by adjusting for age and National Comprehensive Cancer Network risk category. Results: Of 8305 men identified as receiving primary RT, 6368 met the inclusion criteria for CRT (n = 4482) and HRT (n = 1886). The median age was 73.1 years (IQR, 68.2-77.3 years), 2.6% (168) had low risk, 45.7% (2911) had intermediate risk, 44.5% (2836) had high-/very high-risk, and 7.1% (453) had regional nodal disease. Use of HRT increased from 2.1% (9 of 435) in the first half of 2016 to 52.7% (539 of 1023) in the second half of 2019, with lower uptake in the high-/very high-risk (1.9% [4 of 215] to 42.4% [181 of 427]) compared with the intermediate-risk group (2.2% [4 of 185] to 67.6% [325 of 481]) (odds ratio, 0.26; 95% CI, 0.15-0.45). Substantial variability in the use of HRT for intermediate-risk disease remained at the institutional level (median 53.3%; range, 0%-100%) and clinician level (median 57.9%; range, 0%-100%) in the last 2 years of the study period. There were no clinically significant differences across EPIC-26 urinary and bowel functional domains or bother scores. Conclusions and Relevance: In this cohort study, use of HRT for prostate cancer increased substantially from 2016. This population-level data demonstrated clinically equivalent PROs and supports the continued implementation of HRT into routine practice. The wide variation in practice observed at the jurisdictional, institutional, and clinician level provides stakeholders with information that may be useful in targeting implementation strategies and benchmarking services.

Intra-operative cell salvage in urological surgery: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: To evaluate systematically the safety and efficacy of intra-operative cell salvage (ICS) in urology. METHODS: A search of Medline, Embase and Cochrane Library to August 2017 was performed using methods pre-published on PROSPERO. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Eligible titles were comparative studies published in English that used ICS in urology. Primary outcomes were allogeneic transfusion rates (ATRs) and tumour recurrence. Secondary outcomes were complications and cost. RESULTS: Fourteen observational studies were identified, with a total of 4 536 patients. ICS was compared with no the blood conservation technique (seven studies), preoperative autologous donation (PAD; five studies) or both (two studies). Cohorts underwent open prostatectomy (11 studies), open cystectomy (two studies) or open partial nephrectomy (one study). Meta-analysis was possible only for ATRs within prostatectomy studies. In this setting, ICS reduced ATR compared with no the blood conservation technique (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.15-0.76) but not PAD (OR 0.76, 95% CI 0.39-1.31). In the non-prostatectomy setting, ATRs amongst patients who underwent ICS were significantly higher or similar in one and two studies, respectively. Tumour recurrence was found to be significantly less common (two studies), similar (eight studies) or not measured (four studies). All six studies reporting complications found no difference in their ICS cohorts. Regarding cost, one study from 1995 found ICS more expensive than PAD, while two more recent studies found ICS to be cheaper than no blood conservation technique. As a result of inter-study heterogeneity, meta-analyses were not possible for recurrence, complications or cost. CONCLUSION: Low-level evidence exists that, compared with other blood conservation techniques, ICS reduces ATR and cost while not affecting complications. It does not appear to increase tumour recurrence post-prostatectomy, although follow-up durations were short. Small study sizes and short follow-ups mean conclusions cannot be drawn with regard to recurrence after nephrectomy or cystectomy. Randomized trials with long-term follow-up evaluating ICS in urology are required.

2018 Consensus statement on exercise therapy and physical interventions (orthoses, taping and manual therapy) to treat patellofemoral pain: recommendations from the 5th International Patellofemoral Pain Research Retreat, Gold Coast, Australia, 2017.

Patellofemoral pain affects a large proportion of the population, from adolescents to older adults, and carries a substantial personal and societal burden. An international group of scientists and clinicians meets biennially at the International Patellofemoral Research Retreat to share research findings related to patellofemoral pain conditions and develop consensus statements using best practice methods. This consensus statement, from the 5th International Patellofemoral Research Retreat held in Australia in July 2017, focuses on exercise therapy and physical interventions (eg, orthoses, taping and manual therapy) for patellofemoral pain. Literature searches were conducted to identify new systematic reviews and randomised controlled trials (RCTs) published since the 2016 Consensus Statement. The methodological quality of included systematic reviews and RCTs was graded using AMSTAR and PEDro, respectively. Evidence-based statements were developed from included papers and presented to a panel of 41 patellofemoral pain experts for consensus discussion and voting. Recommendations from the expert panel support the use of exercise therapy (especially the combination of hip-focused and knee-focused exercises), combined interventions and foot orthoses to improve pain and/or function in people with patellofemoral pain. The use of patellofemoral, knee or lumbar mobilisations in isolation, or electrophysical agents, is not recommended. There is uncertainty regarding the use of patellar taping/bracing, acupuncture/dry needling, manual soft tissue techniques, blood flow restriction training and gait retraining in patients with patellofemoral pain. In 2017, we launched the International Patellofemoral Research Network (www.ipfrn.org) to consolidate and grow our patellofemoral research community, facilitate collaboration and disseminate patellofemoral pain knowledge to clinicians and the general public. The 6th International Patellofemoral Research Retreat will be held in Milwaukee, Wisconsin, USA, in October 2019.

Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR.

Hepatocellular carcinoma (HCC) is one of the most serious and deadly diseases worldwide with limited options for effective treatment. Biomarker-based active compound targeting therapy may shed some light on novel drugs for HCC. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) play important roles in the regulation of cell fate and have become novel signaling targets for the development of anticancer drugs. Celastrol, a triterpene from traditional Chinese medicine, has been reported to possess anti-tumor effects on various cancers. We, along with several other research groups, have recently reported that UPR was induced by celastrol in several different cancers, including hepatocellular carcinoma. However, UPR status in HCC still remains unclear. The role of ER stress and autophagy in response to celastrol also has yet to be elucidated. Our results demonstrated that celastrol could cause G2/M phase rest and inhibit proliferation in HepG2 and Bel7402. Exposure to celastrol resulted in the activation of the intrinsic apoptotic pathway, via ER stress and the UPR. In murine syngeneic model studies celastrol inhibited H22 tumor growth via the induction of ER stress and apoptosis. Our study suggests that celastrol is a potential drug for HCC therapy via targeting ER-stress/UPR.

A retrospective analysis of Victorian and South Australian clinical registries for prostate cancer: trends in clinical presentation and management of the disease.

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed malignancy reported to Australian cancer registries with numerous studies from individual registries summarizing diagnostic and treatment characteristics. The aim of this study was to describe annual trends in clinical and treatment characteristics, and changes in surveillance practice within a large combined cohort of men with PCa in South Australia (SA) and Victoria, Australia in 2008-2013. METHODS: Common data items from clinical registries in SA and Victoria were merged to develop a cross-jurisdictional dataset consisting of 13,598 men with PCa. Frequencies were used to describe these variables using the National Comprehensive Cancer Network risk of disease progression categories in 10 year age groups. A logistic regression analysis was performed to assess the impact of a number of factors (both individually and together) on the likelihood of men receiving no active treatment within twelve months of the diagnosis (i.e. managed with active surveillance/watchful waiting). RESULTS: Trend analysis showed that over time: (1) men in SA and Victoria are being diagnosed at older age in 2013, 66.1 (SD = 9.7) years compared to 2009 (64.5 (SD = 9.7)); (2) diagnostic methods and characteristics have changed with time; and (3) types of the treatments have changed, with more men having no active treatment. The majority of men were diagnosed with Prostate-Specific Antigen (PSA) <10 ng/mL (66 %) and Grade Group < 4 (65 %). Nearly seventy percent received radical treatment within 12 months of diagnosis, while ~20 % had no active treatment. In 14 % of cases treatment was not recorded or had not commenced. Having no active treatment was strongly associated older age, lower PSA and lower Grade Group at diagnosis, and in 2013 it was offered more frequently (more than 3 times) than in 2009 (OR = 2.63, 95 % CI: 2.16-3.22). CONCLUSIONS: Findings of this study provide the first cross-jurisdictional description of PCa characteristics and management in Australia. These findings will provide benchmarking for ongoing monitoring and feedback of disease management and outcomes of PCa through the Prostate Cancer Outcomes Registry-Australia New Zealand to improve evidence-based practice.

Clinical utility of transcutaneous bilirubinometer (TcB) in very low birth weight (VLBW) infants.

OBJECTIVE: This is a comprehensive study designed to evaluate the clinical usefulness of transcutaneous bilirubinometry (TcB) in very low birth weight (VLBW) newborns of African American (AA) descent. METHODS: TcB was conducted at the anterior superior iliac spine (ASIS), temporal region and sternum within 2 h of total serum bilirubin (TSB) measurements in newborns born at ≤32 weeks' gestation prospectively. Average (AVG) TcB levels were also calculated. The relationships between TSB and TcB levels were analyzed using non-parametric Spearman bivariate correlations, a Bland-Altman plot procedure and a decision tree (DT) analysis. RESULTS: One hundred newborns and 555 TSB data points were available. Eighty-nine percent of the newborns were AA. A significant correlation (P<0.0001) was observed between TSB and TcB values obtained at the ASIS (r=0.73), sternum (0.73), temporal region (0.61) and AVG (0.77). The Bland-Altman plot revealed a good agreement between AVG TcB values and TSB values. A DT analysis indicated that AVG TcB was also found to be the most significant predictor of TSB values in both the no phototherapy (PT) and biliblanket subgroups. CONCLUSION: TcB can be used reliably in VLBW AA newborns in the absence of overhead PT. The use of TcB in monitoring jaundice in VLBW newborns would help decrease the number of blood draws and cost of care.

Celastrol induces unfolded protein response-dependent cell death in head and neck cancer.

The survival rate for patients with oral squamous cell carcinoma (OSCC) has not seen marked improvement in recent decades despite enhanced efforts in prevention and the introduction of novel therapies. We have reported that pharmacological exacerbation of the unfolded protein response (UPR) is an effective approach to killing OSCC cells. The UPR is executed via distinct signaling cascades whereby an initial attempt to restore folding homeostasis in the endoplasmic reticulum during stress is complemented by an apoptotic response if the defect cannot be resolved. To identify novel small molecules able to overwhelm the adaptive capacity of the UPR in OSCC cells, we engineered a complementary cell-based assay to screen a broad spectrum of chemical matter. Stably transfected CHO-K1 cells that individually report (luciferase) on the PERK/eIF2α/ATF4/CHOP (apoptotic) or the IRE1/XBP1 (adaptive) UPR pathways, were engineered [1]. The triterpenoids dihydrocelastrol and celastrol were identified as potent inducers of UPR signaling and cell death in a primary screen and confirmed in a panel of OSCC cells and other cancer cell lines. Biochemical and genetic assays using OSCC cells and modified murine embryonic fibroblasts demonstrated that intact PERK-eIF2-ATF4-CHOP signaling is required for pro-apoptotic UPR and OSCC death following celastrol treatment.

Complementary cell-based high-throughput screens identify novel modulators of the unfolded protein response.

Despite advances toward understanding the prevention and treatment of many cancers, patients who suffer from oral squamous cell carcinoma (OSCC) confront a survival rate that has remained unimproved for more than 2 decades, indicating our ability to treat them pharmacologically has reached a plateau. In an ongoing effort to improve the clinical outlook for this disease, we previously reported that an essential component of the mechanism by which the proteasome inhibitor bortezomib (PS-341, Velcade) induced apoptosis in OSCC required the activation of a terminal unfolded protein response (UPR). Predicated on these studies, the authors hypothesized that high-throughput screening (HTS) of large diverse chemical libraries might identify more potent or selective small-molecule activators of the apoptotic arm of the UPR to control or kill OSCC. They have developed complementary cell-based assays using stably transfected CHO-K1 cell lines that individually assess the PERK/eIF2α/CHOP (apoptotic) or the IRE1/XBP1 (adaptive) UPR subpathways. An 66 K compound collection was screened at the University of Michigan Center for Chemical Genomics that included a unique library of prefractionated natural product extracts. The mycotoxin methoxycitrinin was isolated from a natural extract and found to selectively activate the CHOP-luciferase reporter at 80 µM. A series of citrinin derivatives was isolated from these extracts, including a unique congener that has not been previously described. In an effort to identify more potent compounds, the authors examined the ability of citrinin and the structurally related mycotoxins ochratoxin A and patulin to activate the UPR. Strikingly, it was found that patulin at 2.5 to 10 µM induced a terminal UPR in a panel of OSCC cells that was characterized by an increase in CHOP, GADD34, and ATF3 gene expression and XBP1 splicing. A luminescent caspase assay and the induction of several BH3-only genes indicated that patulin could induce apoptosis in OSCC cells. These data support the use of this complementary HTS strategy to identify novel modulators of UPR signaling and tumor cell death.

Barriers to addressing overweight and obesity before conception.

OBJECTIVE: To investigate the issues that confront women when addressing overweight and obesity before conception. DESIGN: Questionnaire-based study of 412 unselected women in early pregnancy. SETTING AND PARTICIPANTS: 255 women who attended a public, antenatal "first visit" clinic at a major urban obstetric hospital in Brisbane and 157 women who presented to a private obstetrician in Brisbane for a routine ultrasound scan during a 6-week period in 2006 were surveyed. MAIN OUTCOME MEASURES: Preconception health activities, prepregnancy body mass index (BMI), self-reported weight category, attempts to lose weight before pregnancy, and weight loss advice received before pregnancy. RESULTS: Folic acid supplementation was reported by 56% of participants, and 53% attended a preconception health check. Of women who provided details of height and prepregnancy weight, 30% were overweight or obese before pregnancy. However, 23 of 65 women with a BMI in the overweight range categorised themselves as normal weight (36%), and only 8 of 50 women with a BMI in the obese range categorised themselves as obese (16%). As BMI increased, more women reported trying to lose weight (P < 0.001) and reported receiving advice regarding weight loss (P < 0.001). Prepregnancy weight loss was reported by 52 of 115 overweight and obese women (45%). CONCLUSIONS: Potential barriers to addressing overweight and obesity before pregnancy include poor uptake of routine prepregnancy health activities, inaccurate self-categorisation of weight, unsuccessful weight loss attempts and inadequate advice regarding prepregnancy weight loss.

Pulsed electromagnetic energy treatment offers no clinical benefit in reducing the pain of knee osteoarthritis: a systematic review.

BACKGROUND: The rehabilitation of knee osteoarthritis often includes electrotherapeutic modalities as well as advice and exercise. One commonly used modality is pulsed electromagnetic field therapy (PEMF). PEMF uses electro magnetically generated fields to promote tissue repair and healing rates. Its equivocal benefit over placebo treatment has been previously suggested however recently a number of randomised controlled trials have been published that have allowed a systematic review to be conducted. METHODS: A systematic review of the literature from 1966 to 2005 was undertaken. Relevant computerised bibliographic databases were searched and papers reviewed independently by two reviewers for quality using validated criteria for assessment. The key outcomes of pain and functional disability were analysed with weighted and standardised mean differences being calculated. RESULTS: Five randomised controlled trials comparing PEMF with placebo were identified. The weighted mean differences of the five papers for improvement in pain and function, were small and their 95% confidence intervals included the null. CONCLUSION: This systematic review provides further evidence that PEMF has little value in the management of knee osteoarthritis. There appears to be clear evidence for the recommendation that PEMF does not significantly reduce the pain of knee osteoarthritis.

Electric muscle stimulation of the quadriceps in the treatment of patellofemoral pain.

OBJECTIVE: To compare a commercially available electric muscle stimulation regimen with a novel form of stimulation for the rehabilitation of the quadriceps muscle, in patients with patellofemoral pain syndrome. DESIGN: Double-blinded randomized trial with a parallel control group and stratified randomization. SETTING: Home-based rehabilitation program assessed in research center. PARTICIPANTS: Eighty patients (47 women, 33 men) with patellofemoral pain syndrome. INTERVENTIONS: One group (EMPI) received 1 uniform constant frequency component of 35Hz. The other (EXPER) group received an experimental form of stimulation that contained 5 simultaneously delivered frequency components of 125, 83, 50, 2.5, and 2Hz. Stimulation was applied to the quadriceps muscles of the affected leg for 1 hour daily for 6 weeks, a total of 42 treatments. MAIN OUTCOME MEASURES: Lower-limb isometric and isokinetic torque, quadriceps fatigue, knee flexion, patellar pain, a step test, quadriceps cross-sectional area, and Kujala patellofemoral score for pain before and after treatment. RESULTS: Seventy-four patients (43 women, 31 men) completed the trial. Patients in both groups showed significant improvements in all outcomes (P<.05). No significant differences existed between the 2 stimulators in any outcome (P>.05) except for quadriceps cross-sectional area (P=.023). CONCLUSIONS: One form of stimulation was just as efficacious as the other in improving subjective and objective measures.

Motor Imagery Boosts Proprioceptive Neuromuscular Facilitation in the Attainment and Retention of Range-of -Motion at the Hip Joint.

This study examined the effect of proprioceptive neuromuscular facilitation (PNF) coupled with an internal mental imagery technique (PNFI) on both the attainment and retention of increased range-of-movement (ROM) at the hip joint. Twenty-four young adult subjects were randomly allocated to PNF, PNFI, and control treatments administered in fifteen sessions over a three-week period. ROM was assessed prior to training then at the completion of sessions 1 day, 3, 7, and 14 during training, then 28 days after program completion. Analysis-of-Variance with repeated measures showed both significant treatment (p < 0.01) and time effects (p < 0.05). Mean change of ROM values were always larger under the PNFI condition and significantly different (p < 0.05) at day 1 and 3 following training program completion. Thereafter, the diminution of ROM was comparable to the PNF condition. Mean ROM increment relative to baseline was 7.55 and 9.45 degrees for PNF and PNFI respectively receding to 5.86 and 6.5 degrees at twenty-eight days following treatment cessation. Motor imagery coupled with PNF to enhance and retain ROM yields superior results to physical training used alone and can benefit both athletes and those undergoing rehabilitation. Key PointsA Proprioceptive Neuromuscular Facilitation (PNF) technique applied to enhance range-of-movement (ROM) at the hip joint was successful.The effect produced greater gains in participants who received and applied a motor imagery technique to supplement the regular PNF.Both effects receded by about 50% across a no-practice period of 21 days.Incorporation of motor imagery with physical therapy deemed worthwile.