Extracorporeal shockwave therapy for the treatment of lower limb intermittent claudication: Study protocol for a randomised controlled trial (the SHOCKWAVE 1 trial)

© 2017 The Author(s). Background: Peripheral arterial disease (PAD) has a population prevalence of 4.6% with intermittent claudication (IC) presenting as one of the earliest and most common symptoms. PAD has detrimental effects on patients' walking ability in terms of maximum walking distance (MWD) and pain-free walking distance (PFWD). Research has suggested extracorporeal shockwave therapy (ESWT) may induce angiogenesis in treated tissue; therefore, our objective is to assess the tolerability and efficacy of ESWT as a novel treatment of intermittent claudication. Methods/design: Patients with unilateral claudication will be randomised to receive either ESWT (PiezoWave 2 shockwave system) or sham treatment to the calf muscle bulk three times per week for 3 weeks. All patients are blinded to treatment group, and all assessments will be performed by a masked assessor. Treatment tolerability using a visual analogue scale, ankle-brachial pressure index, MWD, PFWD and safety will all be formally assessed as outcome measures at baseline and at 4, 8 and 12 weeks follow-up. Discussion: This trial will be the first of its kind in terms of methodology in relation to ESWT for intermittent claudication. A double-masked randomised controlled trial will provide useful information about the potential for the use of ESWT as a non-invasive treatment option and the need for further robust research. Trial registration: ClinicalTrials.gov, NCT02652078. Registered on 17 October 2014

“Intermittent claudication a real pain in the calf”—Patient experience of diagnosis and treatment with a supervised exercise program

© 2017 Society for Vascular Nursing, Inc. Intermittent claudication (IC) is a common condition which has severe impacts on quality of life, physical function, and mental health. Supervised exercise is the recommended first-line treatment for patients with this condition; however, these are not always feasible or accessible to patients. As the proportion of patients who have this treatment remains suboptimal, it is important to better understand the perception of exercise in this population. A gap in the literature exists about the barriers and facilitators to exercise in patients completing, dropping out of, or declining an exercise program. A qualitative analysis was undertaken to understand this further. Twenty-five patients were interviewed face to face, 10 who had completed exercise, 10 who had declined, and 5 who had dropped out of an exercise program. Three major themes emerged from the data, IC, and perception to exercise and experience or beliefs of the exercise program.Addressing the barriers and facilitators to exercise in patients with IC is crucial in optimizing the delivery and uptake of exercise programs. More education or time investment is needed with these patients during initial diagnostic to help overcome perceived barriers and emphasis healthy behavioral changes

A pilot feasibility randomised clinical trial comparing dialkylcarbamoylchloride-coated dressings versus standard care for the primary prevention of surgical site infection

A surgical site infection (SSI) may occur in up to 30% of procedures and results in significant morbidity and mortality. We aimed to assess the feasibility of conducting a randomised controlled trial (RCT) examining the use of dialkylcarbamoylchloride (DACC)-impregnated dressings, which bind bacteria at the wound bed, in the prevention of SSI in primarily closed incisional wounds. This pilot RCT recruited patients undergoing clean or clean-contaminated vascular surgery. Participants were randomised intraoperatively on a 1:1 basis to either a DACC-coated dressing or a control dressing. Outcomes were divided into feasibility and clinical outcomes. The primary clinical outcome was SSI at 30 days (assessed using Centers for Disease Control criteria and Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of the deep tissues, Isolation of bacteria and duration of inpatient Stay scoring methods). This study recruited 144 patients in 12 months at a median rate of 10 per month. Eligibility was 73% and recruitment 60%. At 30 days, there was a 36.9% relative risk reduction in the DACC-coated arm (16.22% versus 25.71%, odds ratio 0.559, P = 0.161). The number needed to treat was 11 patients. A large-scale RCT is both achievable and desirable given the relative risk reduction shown in this study. Further work is needed to improve the study protocol and involve more centres in a full-scale RCT

Murine models of renal ischemia reperfusion injury: An opportunity for refinement using noninvasive monitoring methods

BACKGROUND: Renal ischemia reperfusion injury (R‐IRI) can cause acute kidney injury (AKI) and chronic kidney disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small‐animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function noninvasively in small rodents allow successful refinement of the R‐IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD. METHODS: Male BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anesthetic. Transdermal GFR monitoring and multispectral optoacoustic tomography (MSOT) in combination with statistical analysis were used to identify and standardize variables within these models. RESULTS: Pre‐clamping anesthetic time was one of the most important predictors of AKI severity after R‐IRI. Standardizing pre‐clamping time resulted in a more predictably severe AKI model. In the CKD model, MSOT demonstrated initial improvement in renal function, followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD with minimal mortality. CONCLUSIONS: Noninvasive monitoring of global and individual renal function after R‐IRI is feasible and reproducible. These techniques can facilitate refinement of kidney injury models and enable the degree of injury seen in preclinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, noninvasive manner

Acetate Kinase Isozymes Confer Robustness in Acetate Metabolism

Acetate kinase (ACK) (EC no: 2.7.2.1) interconverts acetyl-phosphate and acetate to either catabolize or synthesize acetyl-CoA dependent on the metabolic requirement. Among all ACK entries available in UniProt, we found that around 45% are multiple ACKs in some organisms including more than 300 species but surprisingly, little work has been done to clarify whether this has any significance. In an attempt to gain further insight we have studied the two ACKs (AckA1, AckA2) encoded by two neighboring genes conserved in Lactococcus lactis (L. lactis) by analyzing protein sequences, characterizing transcription structure, determining enzyme characteristics and effect on growth physiology. The results show that the two ACKs are most likely individually transcribed. AckA1 has a much higher turnover number and AckA2 has a much higher affinity for acetate in vitro. Consistently, growth experiments of mutant strains reveal that AckA1 has a higher capacity for acetate production which allows faster growth in an environment with high acetate concentration. Meanwhile, AckA2 is important for fast acetate-dependent growth at low concentration of acetate. The results demonstrate that the two ACKs have complementary physiological roles in L. lactis to maintain a robust acetate metabolism for fast growth at different extracellular acetate concentrations. The existence of ACK isozymes may reflect a common evolutionary strategy in bacteria in an environment with varying concentrations of acetate

Constantly connected – The effects of smart-devices on mental health

A number of studies have demonstrated the mental health implications of excessive Internet-browsing, gaming, texting, emailing, social networking, and phone calling. However, no study to date has investigated the impact of being able to conduct all of these activities on one device. A smart-device (i.e., smart-phone or tablet) allows these activities to be conducted anytime and anywhere, with unknown mental health repercussions. This study investigated the association between smart-device use, smart-device involvement and mental health. Two-hundred and seventy-four participants completed an online survey comprising demographic questions, questions concerning smart-device use, the Mobile Phone Involvement Questionnaire, the Internet Addiction Test and the Depression, Anxiety and Stress Scales. Higher smart-device involvement was significantly associated with higher levels of depression and stress but not anxiety. However, smart-device use was not significantly associated with depression, anxiety or stress. These findings suggest that it is the nature of the relationship a person has with their smart-device that is predictive of depression and stress, rather than the extent of use

Minimizing Errors in RT-PCR Detection and Quantification of SARS-CoV-2 RNA for Wastewater Surveillance

Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.Highlights: Harmonized QA/QC procedures for SARS-CoV-2 wastewater surveillance are lacking; Wastewater analysis protocols are not optimized for trace analysis of viruses; False-positive and -negative errors have consequences for public health responses; Inter-laboratory studies utilizing standardized reference materials and protocols are needed.info:eu-repo/semantics/publishedVersio

Analysis of Tp53 Codon 72 Polymorphisms, Tp53 Mutations, and HPV Infection in Cutaneous Squamous Cell Carcinomas

Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism).We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations