Aperiodic and Hurst EEG exponents across early human brain development: A systematic review.

In electroencephalographic (EEG) data, power-frequency slope exponents (1/f_ß) can provide non-invasive markers of in vivo neural activity excitation-inhibition (E:I) balance. E:I balance may be altered in neurodevelopmental conditions; hence, understanding how 1/fß evolves across infancy/childhood has implications for developing early assessments/interventions. This systematic review (PROSPERO-ID: CRD42023363294) explored the early maturation (0-26 yrs) of resting-state EEG 1/f measures (aperiodic [AE], power law [PLE] and Hurst [HE] exponents), including studies containing ≥1 1/f measures and ≥10 typically developing participants. Five databases (including Embase and Scopus) were searched during March 2023. Forty-two studies were identified (Nparticipants=3478). Risk of bias was assessed using the Quality Assessment with Diverse Studies tool. Narrative synthesis of HE data suggests non-stationary EEG activity occurs throughout development. Age-related trends were complex, with rapid decreases in AEs during infancy and heterogenous changes thereafter. Regionally, AE maxima shifted developmentally, potentially reflecting spatial trends in maturing brain connectivity. This work highlights the importance of further characterising the development of 1/f measures to better understand how E:I balance shapes brain and cognitive development.

Evaluation of short exposure times of antimicrobial wound solutions against microbial biofilms: from in vitro to in vivo.

Objectives: Test the performance of topical antimicrobial wound solutions against microbial biofilms using in vitro, ex vivo and in vivo model systems at clinically relevant exposure times. Methods: Topical antimicrobial wound solutions were tested under three different conditions: (in vitro) 4% w/v Melaleuca oil, polyhexamethylene biguanide, chlorhexidine, povidone iodine and hypochlorous acid were tested at short duration exposure times for 15 min against 3 day mature biofilms of Staphylococcus aureus and Pseudomonas aeruginosa; (ex vivo) hypochlorous acid was tested in a porcine skin explant model with 12 cycles of 10 min exposure, over 24 h, against 3 day mature P. aeruginosa biofilms; and (in vivo) 4% w/v Melaleuca oil was applied for 15 min exposure, daily, for 7 days, in 10 patients with chronic non-healing diabetic foot ulcers complicated by biofilm. Results: In vitro assessment demonstrated variable efficacy in reducing biofilms ranging from 0.5 log10 reductions to full eradication. Repeated instillation of hypochlorous acid in a porcine model achieved <1 log10 reduction (0.77 log10, P = 0.1). Application of 4% w/v Melaleuca oil in vivo resulted in no change to the total microbial load of diabetic foot ulcers complicated by biofilm (median log10 microbial load pre-treatment = 4.9 log10 versus 4.8 log10, P = 0.43). Conclusions: Short durations of exposure to topical antimicrobial wound solutions commonly utilized by clinicians are ineffective against microbial biofilms, particularly when used in vivo. Wound solutions should not be used as a sole therapy and clinicians should consider multifaceted strategies that include sharp debridement as the gold standard.

Next Generation DNA Sequencing of Tissues from Infected Diabetic Foot Ulcers.

We used next generation DNA sequencing to profile the microbiome of infected Diabetic Foot Ulcers (DFUs). The microbiota was correlated to clinical parameters and treatment outcomes to determine if directed antimicrobial therapy based on conventional microbiological cultures are relevant based on genomic analysis. Patients≥18years presenting with a new Diabetic Foot Infection (DFI) who had not received topical or oral antimicrobials in the two weeks prior to presentation, were eligible for enrolment. Tissue punch biopsies were obtained from infected DFUs for analysis. Demographics, clinical and laboratory data were collected and correlated against microbiota data. Thirty-nine patients with infected DFUs were recruited over twelve-months. Shorter duration DFUs (

Effect of cadexomer iodine on the microbial load and diversity of chronic non-healing diabetic foot ulcers complicated by biofilm in vivo.

Objectives: The performance of cadexomer iodine was determined against microbial populations from chronic non-healing diabetic foot ulcers (DFUs) complicated by biofilm in vivo , using molecular, microscopy and zymography methods. Methods: Chronic non-healing DFUs due to suspected biofilm involvement were eligible for enrolment. DNA sequencing and real-time quantitative PCR was used to determine the microbial load and diversity of tissue punch biopsies obtained pre- and post-treatment. Scanning electron microscopy and/or fluorescence in situ hybridization confirmed the presence or absence of biofilm. Zymography was used to determine levels of wound proteases. Results: Seventeen participants were recruited over a 6 month period. Scanning electron microscopy and or fluorescence in situ hybridization confirmed the presence of biofilm in all samples. Eleven participants exhibited log 10 reductions in microbial load after treatment (range 1-2 log 10 ) in comparison with six patients who experienced <1 log 10 reduction ( P = 0.04). Samples were tested for levels of wound proteases pre- and post-treatment. Reductions in the microbial load correlated to reductions in wound proteases pre- and post-treatment ( P = 0.03). Conclusions: To the best of our knowledge, this study represents the first in vivo evidence, employing a range of molecular and microscopy techniques, of the ability of cadexomer iodine to reduce the microbial load of chronic non-healing DFUs complicated by biofilm. Further analyses correlating log reductions to optimal duration of therapy and improvements in clinical parameters of wound healing in a larger cohort are required.

Can molecular DNA-based techniques unravel the truth about diabetic foot infections?

Diabetes foot infections are a common condition and a major causal pathway to lower extremity amputation. Identification of causative pathogens is vital in directing antimicrobial therapy. Historically, clinicians have relied upon culture-dependent techniques that are now acknowledged as both being selective for microorganisms that thrive under the physiological and nutritional constraints of the microbiology laboratory and that grossly underestimate the microbial diversity of a sample. The amplification and sequence analysis of the 16S rRNA gene has revealed a diversity of microorganisms in diabetes foot infections, extending the view of the diabetic foot microbiome. The interpretation of these findings and their relevance to clinical care remains largely unexplored. The advent of molecular methods that are culture-independent and employ massively parallel DNA sequencing technology represents a potential 'game changer'. Metagenomics and its shotgun approach to surveying all DNA within a sample (whole genome sequencing) affords the possibility to characterize not only the microbial diversity within a diabetes foot infection (i.e. 'which microorganisms are present') but the biological functions of the community such as virulence and pathogenicity (i.e. 'what are the microorganisms capable of doing'), moving the focus from single species as pathogens to groups of species. This review will examine the new molecular techniques for exploration of the microbiome of infected and uninfected diabetic foot ulcers, exploring the potential of these new technologies and postulating how they could translate to improved clinical care. Copyright © 2016 John Wiley & Sons, Ltd.

Venous Malformation and Localized Intravascular Coagulopathy in Children.

Aim Localized intravascular coagulopathy (LIC) has been described in adults with venous malformation (VM) but rarely reported in children. This study aims to determine the prevalence of LIC in children with VM and associated risk factors. Methods Patients younger than 18 years with VM from 2010 to 2014 were reviewed. Diagnosis was confirmed by Doppler ultrasound and/or magnetic resonance imaging. Demographics data and VM characteristics including volume, site, extension, painful symptoms, and palpable phleboliths were studied. Plasma D-dimer level of greater than 500 ng/mL was considered as abnormal. Results Total 24 children were included, of whom 8 were boys. Median age of presentation was 9 months (range: 0-12 years). Head-and-neck VM occurred in 17 (70.8%) patients and 3 (12.5%) had multifocal lesions. Seven (29.2%) patients had VM volume greater than 10 mL. Five (20.8%) patients had painful symptoms. Palpable phleboliths were found in two patients. Plasma D-dimer was raised in eight cases (33.3%). One patient with Klippel-Trenaunay syndrome (KTS) had D-dimer level of 5,000 ng/mL. Raised D-dimer was found in 23.5% of small VM (volume < 10 mL) and 57.1% of large VM (p = 0.167). D-dimer was significantly raised in multifocal VM (p = 0.028) and showed increasing trend in lesions with palpable phleboliths (p = 0.101). All patients had sclerotherapy performed with indications (cosmesis 41.7%, enlarging lesion 29.2%, pain 20.8%, bleeding 8.3%). Perioperatively, bolus intravenous fluid and mannitol were given to selected patients. All patients had VM volume reduction after sclerotherapy. There were no major thromboembolic complications. Conclusion LIC with raised D-dimer level occurred in one-third of pediatric VM. It was more common in large, multifocal VM and in those with palpable phleboliths or KTS.

Primary care referral to multidisciplinary high risk foot services - too few, too late.

BACKGROUND: To determine if patients with no contact with a multi-disciplinary team High Risk Foot Service (MDT-HRFS) had an increased rate of hospital admission for diabetes foot infection compared to patients with contact. Secondary aims were to report on clinical outcomes. METHODS: A retrospective study was conducted at a major tertiary referral hospital in metropolitan Sydney over 12 months. An ICD-10 search of the electronic medical record system and paper medical charts identified patients with diabetes mellitus (type 1 or type 2) and a primary admission for diabetes foot infection (DFI). Patients were categorised as having contact or no contact with an MDT-HRFS. RESULTS: One hundred ninety-six hospital admissions (156 patients) were identified with DFI over a 12-month period. Patients with no contact with a MDT-HRFS represented three quarters of admissions (no contact = 116, 74.7 % vs. contact = 40, 25.6 %, p = 0.0001) and presented with more severe infection (no contact = 39 vs. contact = 12). The odds of lower extremity amputation increased five-fold when both no contact and severe infection occurred in combination (no contact with severe infection and amputation = 34, 82.9 % vs. contact with severe infection and amputation = 7, 17.1 %, OR 4.9, 95 % CI 1.1-21.4, p = 0.037). Using estimates of both the contact and no contact population of people with diabetes and high-risk feet and assuming the risk of amputation was the same, than the number of expected amputations in the no contact group should have been 55, however the observed number was 77, 22 more than expected (p = 0.0001). CONCLUSIONS: Patients with no contact with a MDT-HRFS represented the majority of admissions for DFIs to a tertiary referral hospital. This group on population estimates appears to be at high risk of amputation of the lower extremity and therefore early referral of this high-risk group might lower this risk.

The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other comorbidities on length of stay (LOS) and costs in patients with peripheral arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A retrospective study was conducted between January 2011 and July 2012 at a tertiary referral hospital in Sydney. Demographic, laboratory, and operative data were obtained from the Australasian Vascular Audit database and hospital diagnostic-related group (DRG) reports. Patients with confirmed PAD with or without DM requiring hospital admission for a diagnosis of claudication, rest pain, ulcer/gangrene, and infection that required lower limb surgical intervention were included. Associations between LOS, surgical procedure, and DRG were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients) were identified: 292 admissions with PAD and 276 admissions with PAD in conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 ± 13.7 days compared with 15 ± 18.2 days for PADDM (p < .01; 95% confidence interval 2.7-8.0). LOS and costs were greatest in patients with PADDM undergoing major amputation (37 ± 13.7 days; US$42,236; p < .01). Analysis of variance indicated that the best predictors of LOS were the presence of DM, bypass surgery, amputation, chronic kidney disease (CKD) stage V, infection, and emergency admission. Over 18 months, the estimated total inpatient costs associated with lower limb intervention for PAD with and without DM amounted to US$7,598,597. People with DM incurred greater inpatient costs, averaging US$1,912 more per episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The impact of diabetes as a comorbid condition in patients with PAD is significant, both clinically and economically. Factors that predict increased LOS in patients with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and emergency admission.

Pedal osteomyelitis in patients with diabetes: a retrospective audit from Saudi Arabia.

OBJECTIVE: To examine the characteristics of patients presenting to the emergency room and the specialist diabetes foot clinic with pedal osteomyelitis (PO). METHOD: A retrospective study was conducted at a regional hospital. The charts of patients with suspected PO who presented during the period 1 January to 31 December 2011 were analysed. Demographics, biochemistry and microbiological data were obtained. Bone biopsies were performed by the attending clinician either during surgical removal of infected bone, or percutaneously under guided fluoroscopy through non-infected tissue. RESULTS: Sixty-six cases of osteomyelitis affecting 102 joints were noted. The study population consisted of 44 men, mean age 62.9 +/- 1.3 years, and 22 women, mean age of 57.6 +/- 10.6 years. Gram-positive bacteria were the predominating pathogens (p < 0.05). Staphylococcus aureus was cultured in 36% of all bone biopsy cases. A predictive trend in HbA1c was observed,where every increase of 1% from the recommended level of 7% was associated with a 10% increase in the likelihood of receiving surgical intervention. CONCLUSION: S. aureus infection is a major cause of osteomyelitis in interphalangeal joints of the feet of diabetic patients.There is an apparent association with patients who present with diabetic foot osteomyelitis and sub-optimal glycaemic control, requiring surgical intervention.

Red flags and alarm bells: an atypical lesion masquerading as a diabetic foot ulcer.

An 88-year-old male presented at a high-risk foot service with a non-healing, plantar wound on his right foot, which had the appearance of a neuropathic ulcer. On further examination, the lesion was confirmed asymmetrical in shape and atypical in appearance. It also presented with surrounding violaceous, pigmented nodules in the arch of the foot, and several small, similar nodules on the plantar surface of the contralateral foot, giving the appearance of an exophytic lesion and suggesting melanoma. Following biopsy, it was diagnosed as classic Kaposi sarcoma.

Meta-analyses of cognitive and motor function in youth aged 16 years and younger who subsequently develop schizophrenia.

BACKGROUND: Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not. METHOD: Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement. RESULTS: Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13. CONCLUSIONS: These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.

Topical anaesthesia alleviates short-term pain of castration and tail docking in lambs.

OBJECTIVE: To investigate the effect of a topical anaesthetic formulation on pain alleviation, wound healing and systemic levels of local anaesthetic actives in lambs undergoing castration and tail docking. DESIGN: Three placebo-controlled and/or randomised experiments were conducted using three groups of Merino lambs (n = 62, 68 and 19) undergoing routine castration and tail docking. PROCEDURE: Surgical castration, with either surgical or hot-iron tail docking, was performed with and without the application of topical anaesthetic (Tri-Solfen) or placebo. The effects of this procedure were compared with those of rubber ring castration and tail docking, and of the handled but unmarked controls. Wound pain was assessed using calibrated Von-Frey monofilaments over a 4-h period, pain-related behaviour was assessed over 5 h, wound healing was assessed at 14 and 28 days, and the plasma levels of lignocaine and bupivacaine were determined. RESULTS: Rapid and up to 4 h primary hyperalgesia developed following surgical castration and tail docking in the untreated and placebo-treated lambs. It was absent in the castration wounds, and significantly reduced in the tail-docking wounds, of the treated lambs. Hot-iron docking was associated with mild and transient secondary hyperalgesia, which was abolished by the topical anaesthesia. There was a significant reduction in pain-related behaviours in treated lambs, which were not significantly different in their behaviour to the sham-operation handled controls. Plasma lignocaine and bupivacaine levels were below the toxic thresholds in all tested lambs. CONCLUSION: Topical anaesthesia alleviates wound pain and significantly reduces pain-related behaviours in lambs undergoing surgical castration plus surgical or hot-iron tail docking, without a negative effect on wound healing or a risk of systemic toxicity.

Agreement of functional independence measure item scores in patients transferred from one rehabilitation setting to another.

AIM: Classification and payment systems that incorporate a functional measure used in routine clinical practice can only be as accurate as the underlying functional measure. The test-retest reliability in clinical practice of the individual item scores of the Functional Independence Measure (FIM), a functional measure used in classification and payment systems has been investigate. The aim of this study was to analyse paired measurements of FIM item scores carried out in routine clinical practice for patients transferred from one Rehabilitation Unit to another, and to determine the interrater reliability using standard measures of agreement and bias. METHODS: Patients who were transferred between two rehabilitation units between August 2006 and October 2007 had a FIM scored on discharge from the original unit and a FIM scored on admission to the second unit. A short time between score and re-score reduced the probability of significant functional change. A retrospective analysis was performed. RESULTS: Paired FIM item scores from143 patients were included in the review. Raw agreement between the two scores for each FIM item was low, with a mean of 54 + 18 pairs (%) matching. The range of difference between scores was wide. Weighted kappa values were generally in the fair agreement range as were the intraclass correlation coefficients. Tests for bias and homogeneity showed that just over half of the items had significant differences in the two sets of scores. Weighted k showed only fair agreement for FIM items. Contributing factors for this could include incomplete FIM training of some staff, insufficient attention to accurate scoring, actual clinical changes, differences between patient performance in different settings, and variation in scoring because of the large number of staff involved in scoring the FIM in the multidisciplinary team within our settings. CONCLUSIONS: Caution needs to be exercised when utilizing the FIM individual item scores in clinical practice as part of clinical or funding classifications or in benchmarking as this study indicates only fair inter-rater reliability of these scores in clinical practice.

"The Happy Migrant Effect": perceptions of negative experiences of healthcare by patients with little or no English: a qualitative study across seven language groups.

BACKGROUND: The subjective experiences of patients with little or no English who either attended the Emergency Department or were admitted to the wards of a tertiary referral hospital were explored. SETTING AND METHODS: The reports of experiences from 49 patients of a tertiary referral hospital were analysed using grounded theory methods applied to translated transcriptions from focus groups held with discharged patients in seven languages. RESULTS: Inability to communicate in English, poor patient and family involvement with staff, a lack of control or powerlessness, staff shortages, staff negligence or incompetence, and treatment delays were reported by some patients. Others tended to discount or minimise the significance of similar experiences, suggesting a construct, "The Happy Migrant Effect," in which there is reluctance to assert healthcare rights. Patients appear "happy" and satisfied, despite problems with their hospital care. Explanatory factors for the construct include extreme powerlessness related to being unable to communicate, a positive comparison of healthcare in the new country compared with the old, patriotism for the new country, cultural norms that proscribe acceptance, politeness or social desirability, self-denigration for not having learnt English and, for a few, a fear of reprisals if they spoke out in complaint. CONCLUSIONS: Some immigrant patients with poor language skills might not report serious problems with healthcare delivery. In all patients in this study where problems with healthcare were reported, the events were considered to be largely preventable by appropriate language facilitation, patient and family involvement, and provider respect and compassion.

The inability to ignore: distractibility in women with restricting anorexia nervosa.

BACKGROUND: Attentional difficulties reported in individuals with anorexia nervosa (AN) may be due to preferential processing of disease-salient stimuli at a pre-attentive or at a conscious level or to a general problem in attention. Attentional difficulties may be associated with duration of illness. METHOD: Female participants with AN (restricting subtype; n=24) and healthy comparison women (n=24) were randomly allocated to subliminal or supraliminal exposure to visual stimuli (food, neutral and aversive images) while performing the 1-back and 2-back working-memory tasks. RESULTS: Participants with AN made fewer errors than the healthy comparison group in the subliminal condition but significantly more errors in the supraliminal condition [condition x group interaction, F(1, 44)=6.82, p<0.01]: this was irrespective of stimulus type (food, neutral and aversive) and task (1-back or 2-back). The total number of errors made correlated positively with the duration of the AN for both the 1-back task (rs=0.46, p<0.05) and for the 2-back task (rs=0.53, p<0.01). CONCLUSIONS: Decreased ability to concentrate in the presence of explicit distracters is a feature of AN and is associated with longer duration of illness. This phenomenon could be addressed in psychological interventions.

Does telephone contact with a physician's office staff improve mammogram screening rates?

BACKGROUND AND OBJECTIVES: Mammography is an important screening tool for the early detection of breast cancer. However, mammogram screening rates are low, despite interventions to improve them. We investigated two methods to improve mammogram screening and compared mammogram rates among women who received these interventions to mammogram screening rates in a control group. We also investigated the costs involved in these interventions. METHODS: We studied mammogram screening rates of three randomized groups of women ages 50 and older from the Deighton Family Practice Center in Southfield, Mich. All women had had a mammogram 1 year previously and were due for another mammogram. Our control group (n = 110) received no intervention. The second group of women (n = 102) received a reminder letter from the radiology department. The third group (n = 86) received a reminder letter followed by a phone call from the physician's office staff if no mammogram had been obtained within 8 weeks after the due date for the mammogram. All three groups were monitored for 14 weeks after the due date to determine mammogram screening rates in each group. RESULTS: A mammogram was obtained by 33% of women in group 1, 37% of women in group 2, and 57% of women in group 3. The mammogram screening rate of the third group was significantly greater than in the first two groups. In the third group, the additional cost added by the phone call intervention was $9 per mammogram obtained. CONCLUSION: Mammogram screening rates are increased when patients are contacted by both a reminder letter and a phone call.