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1.
J Healthc Qual Res ; 2024 May 13.
Article in Spanish | MEDLINE | ID: mdl-38744586

ABSTRACT

INTRODUCTION AND OBJECTIVES: Healthcare organisations are highly complex entities that live with a high risk of instability. In order to minimise this instability, interactions and personal relationships play a major role and accordingly the figure of the leader gains full significance. The leadership style used can produce different reactions and lead to multiple outcomes, including job satisfaction. The aim of the present review is to correlate leadership style with job satisfaction in healthcare professionals. MATERIAL AND METHODS: A systematic review was carried out in BVS, Cochrane plus, CINAHL, ApaPsycinfo and Pubmed, selecting publications that mentioned leadership styles and job satisfaction in healthcare professionals. Publications search strategy were limited for the 5-10last years, full text availability and language of writing: English, French and Spanish. Review-type publications were excluded. Of the 1566 initial titles, 15 were selected for analysis. RESULTS AND CONCLUSIONS: The transformational style showed the highest number of positive correlations, followed by the authentic and transactional styles. On the other hand, the passive and laissez-faire styles showed a negative correlation regardless of the professional category to which they belonged. The results of this study provide a starting point for adopting effective leadership styles to optimise the recruitment and training processes of staff in management and coordination roles.

2.
mBio ; 13(2): e0019522, 2022 04 26.
Article in English | MEDLINE | ID: mdl-35323040

ABSTRACT

Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children (n = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam (r: 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC (r: 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.


Subject(s)
Community-Acquired Infections , Microbiota , Pneumonia , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Community-Acquired Infections/drug therapy , Humans , Infant , Pneumonia/drug therapy , beta-Lactams/therapeutic use
3.
Radiography (Lond) ; 28(3): 823-830, 2022 08.
Article in English | MEDLINE | ID: mdl-35135707

ABSTRACT

INTRODUCTION: Ionizing radiation can cause increased opacity of the lens and later lead to radiation-induced cataract. Therefore, the eye lens should be positioned outside of the direct radiation beam in cranial computed tomography (CCT). If this is not possible, protective measures must be taken, which includes the use of external lens protectors. In this study we assess whether direct radiation exposure of the eyes in CCT can be reduced by trained radiographers and whether the use of eye lens protectors improves after training. METHODS: First, we evaluated 763 non-enhanced CCT regarding direct radiation exposure of eyeballs and eye lenses and usage of lens shielding. Afterwards, we trained radiographers to avoid radiation exposure of the eyes by head adjustment and protectors and assessed the improvements in a subsequent study of 678 CCT. We tried to identify factors that influenced radiation exposure of the eye lens. RESULTS: After training, frequency of radiation exposure of lenses was significantly reduced by 5.9% (220/763 patients in pre- vs. 155/678 patients in post-training group, p = 0.01). The use of external lens protectors significantly increased after training by 9.8% (37/763 patients in pre- vs. 99/678 patients in post-training group, p < 0.001). The absence of tiltable headrest was a risk factor for increased eye lens radiation exposure in the pre-training group. The presence of cervical spine immobilizer was associated with more frequent radiation exposure of the lenses in the pre- and post-training group. CONCLUSIONS: Radiographer training and the use of tiltable headrest lead to reduction of radiation exposure to the eye lens. IMPLICATIONS FOR PRACTICE: Radiographer training is an effective method to reduce eye lens exposure in CCT. The usage of tiltable headrest minimizes the radiation exposure of the lenses.


Subject(s)
Cataract , Lens, Crystalline , Radiation Exposure , Radiation Injuries , Humans , Radiation Exposure/prevention & control , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Tomography, X-Ray Computed/adverse effects
4.
Br J Oral Maxillofac Surg ; 59(3): 265-271, 2021 04.
Article in English | MEDLINE | ID: mdl-33546846

ABSTRACT

The aim of this study was to evaluate the impact of orthognathic surgery on the quality of life (QoL) of patients with dentofacial deformity. This systematic review was performed through the survey of observational studies that had evaluated the impact of orthognathic surgery on the QoL of patients with dentofacial deformity. The article databases included PubMed, Scopus, Web of Science, LILACS, BBO, Cochrane Library, and grey literature. The risk of bias was analysed according to the Newcastle-Ottawa Scale for quality assessment. The meta-analysis was performed considering the exposure before and after orthognathic surgery using the Oral Health Impact Profile (OHIP-14) versus the Orthognathic Quality of Life Questionnaire (OQLQ). A total of 2,263 articles were identified. Twelve studies remained in the qualitative synthesis and seven studies were included in the meta-analysis. The impact of QoL both preoperatively and postoperatively with the OHIP-14 questionnaire was 7.63 (95% confidence interval (CI) = 1.62 to 13.65; p = 0.01) and the OQLQ questionnaire was 20.53 (95% CI = 14.27 to 26.79; p < 0.0001). Overall impact of QoL was 16.01 (95% CI = 10.50 to 21.52; p < 0.0001), which showed that orthognathic surgery has an influence on the QoL. Orthognathic surgery generates positive impact on the QoL of patients with dentofacial deformity.


Subject(s)
Dentofacial Deformities , Orthognathic Surgery , Orthognathic Surgical Procedures , Dentofacial Deformities/surgery , Humans , Quality of Life , Surveys and Questionnaires
5.
S Afr Med J ; 110(10): 988-992, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-33205725

ABSTRACT

Breast cancer is highly prevalent in South Africa, and up to 10% of breast cancer cases may be hereditary. The landscape of genetic testing options for hereditary breast cancer (HBC) has changed significantly over the past decade, and healthcare providers are faced with multiple options when referring breast cancer patients for genetic testing. We have performed a retrospective study of 3 years' worth of breast cancer genetic testing referrals to our laboratory. While Afrikaner and Ashkenazi Jewish founder screens may be appropriate as first-line tests in a limited subset of patients, we have shown that in the majority of cases it is more effective to adopt a multigene panel approach. While variants in the BRCA1 and BRCA2 genes still account for a significant proportion of cases, close to 40% of pathogenic variants were found in genes other than BRCA1 or BRCA2. There are many factors that healthcare providers should consider when requesting genetic testing for breast cancer patients and families, including family history, ancestral background, cost, medical aid scheme reimbursement and scope of testing. We summarise our findings and provide advantages and disadvantages of each approach, with the aim of assisting clinicians and genetic counsellors to make appropriate testing decisions.


Subject(s)
Breast Neoplasms/diagnosis , Genetic Testing , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Founder Effect , Humans , Multifactorial Inheritance , Retrospective Studies , South Africa , Ubiquitin-Protein Ligases/genetics
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1512-1515, 2020 07.
Article in English | MEDLINE | ID: mdl-33018278

ABSTRACT

The patient-clinician relationship is known to significantly affect the pain experience, as empathy, mutual trust and therapeutic alliance can significantly modulate pain perception and influence clinical therapy outcomes. The aim of the present study was to use an EEG hyperscanning setup to identify brain and behavioral mechanisms supporting the patient-clinician relationship while this clinical dyad is engaged in a therapeutic interaction. Our previous study applied fMRI hyperscanning to investigate whether brain concordance is linked with analgesia experienced by a patient while undergoing treatment by the clinician. In this current hyperscanning project we investigated similar outcomes for the patient-clinician dyad exploiting the high temporal resolution of EEG and the possibility to acquire the signals while patients and clinicians were present in the same room and engaged in a face-to-face interaction under an experimentally-controlled therapeutic context. Advanced source localization methods allowed for integration of spatial and spectral information in order to assess brain correlates of therapeutic alliance and pain perception in different clinical interaction contexts. Preliminary results showed that both behavioral and brain responses across the patient-clinician dyad were significantly affected by the interaction style.Clinical Relevance- The context of a clinical intervention can significantly impact the treatment of chronic pain. Effective therapeutic alliance, based on empathy, mutual trust, and warmth can improve treatment adherence and clinical outcomes. A deeper scientific understanding of the brain and behavioral mechanisms underlying an optimal patient-clinician interaction may lead to improved quality of clinical care and physician training, as well as better understanding of the social aspects of the biopsychosocial model mediating analgesia in chronic pain patients.


Subject(s)
Brain , Chronic Pain , Pain Management , Professional-Patient Relations , Brain/physiology , Humans , Magnetic Resonance Imaging , Pain Perception
7.
Eur J Neurol ; 27(11): 2176-2184, 2020 11.
Article in English | MEDLINE | ID: mdl-32558040

ABSTRACT

BACKGROUND AND PURPOSE: Basilar artery occlusion (BAO) leads to high rates of morbidity and mortality, despite successful recanalization. The discordance between flow restoration and long-term functional status clouds clinical decision-making regarding further aggressive care. We sought to develop and validate a practical, prognostic tool for the prediction of 3-month favorable outcome after acute reperfusion therapy for BAO. METHODS: This retrospective, multicenter, observational study was conducted at four high-volume stroke centers in the USA and Europe. Multivariate regression analysis was performed to identify predictors of favorable outcome (90-day modified Rankin scale scores 0-2) and derive a clinically applicable prognostic model (the Pittsburgh Outcomes after Stroke Thrombectomy-Vertebrobasilar (POST-VB) score). The POST-VB score was evaluated and internally validated with regard to calibration and discriminatory ability. External validity was assessed in patient cohorts at three separate centers. RESULTS: In the derivation cohort of 59 patients, independent predictors of favorable outcome included smaller brainstem infarct volume on post-procedure magnetic resonance imaging (P < 0.01) and younger age (P = 0.01). POST-VB score was calculated as: age + (10 × brainstem infarct volume). POST-VB score demonstrated excellent discriminatory ability [area under the receiver-operating characteristic curve (AUC) = 0.91] and adequate calibration (P = 0.88) in the derivation cohort (Center A). It performed equally well across the three external validation cohorts (Center B, AUC = 0.89; Center C, AUC = 0.78; Center D, AUC = 0.80). Overall, a POST-VB score < 49 was associated with an 88% likelihood of favorable outcome, as compared to 4% with a score ≥ 125. CONCLUSIONS: The POST-VB score effectively predicts 3-month functional outcome following acute reperfusion therapy for BAO and may aid in guiding post-procedural care.


Subject(s)
Endovascular Procedures , Stroke , Vertebrobasilar Insufficiency , Basilar Artery/diagnostic imaging , Europe , Humans , Reperfusion , Retrospective Studies , Treatment Outcome
8.
J Neurosci Rural Pract ; 11(2): 222-229, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32367975

ABSTRACT

Tracheostomy is the commonest bedside surgical procedure performed on patients needing mechanical ventilation with traumatic brain injury (TBI). The researchers made an effort to organize a narrative review of the indications, timing, management, complications, and outcomes of tracheostomy in relation to neuronal and brain-injured patients following TBI. The study observations were collated from the published literature, namely original articles, book chapters, case series, randomized studies, systematic reviews, and review articles. Information sorting was restricted to tracheostomy and its association with TBI. Care was taken to review the correlation of tracheostomy with clinical correlates including indications, scheduling, interventions, prognosis, and complications of the patients suffering from mild, moderate and severe TBIs using Glasgow Coma Scale, Glasgow Outcome Scale, intraclass correlation coefficient, and other internationally acclaimed outcome scales. Tracheostomy is needed to overcome airway obstruction, prolonged respiratory failure and as indispensable component of mechanical ventilation due to diverse reasons in intensive care unit. Researchers are divided over early tracheostomy or late tracheostomy from days to weeks. The conventional classic surgical technique of tracheostomy has been superseded by percutaneous techniques by being less invasive with lesser complications, classified into early and late complications that may be life threatening. Additional studies have to be conducted to validate and streamline varied observations to frame evidence-based practice for successful weaning and decannulation. Tracheostomy is a safer option in critically ill TBI patients for which a universally accepted protocol for tracheostomy is needed that can help to optimize indications and outcomes.

10.
Anaesthesist ; 68(11): 733-741, 2019 11.
Article in German | MEDLINE | ID: mdl-31324931

ABSTRACT

Early recanalization of the closed cerebral arteries after acute ischemic stroke (AIS) is the only treatment to minimize long-term disability and to reduce the associated morbidity and mortality. For a long time the only proven causal treatment of AIS was intravenous thrombolysis; however, after the publication of a series of randomized prospective studies concerning endovascular mechanical thrombectomy using stent retriever systems after AIS, new guidelines were published. It was found that endovascular treatment (EVT) dramatically improves the outcome of eligible patients. The stent retriever enables high recanalization rates by clot removal from the cerebral arterial system by means of aspiration of the thrombus via the catheter and/or by entrapping it with a stent system. The management of anesthesia during the procedure is indispensable to prevent hypoxia and hemodynamic instability; however, which form of anesthesia (i.e. general anesthesia vs. conscious sedation) is advantageous for the patient during EVT is controversially discussed. In the first studies using retrospective data conscious sedation resulted in a better outcome compared to general anesthesia following EVT; however, in prospective studies this finding could not be confirmed. To obtain optimal neurological results after AIS and EVT with general anesthesia, it is of tremendous importance not to delay the EVT due to the anesthesiology procedure. Furthermore, hypotension, hypovolemia and hypocapnia should also be strictly avoided. Finally, the optimal anesthesiological approach should be guided by the current clinical state and pre-existing comorbidities of the patient.


Subject(s)
Brain Ischemia/therapy , Endovascular Procedures/methods , Mechanical Thrombolysis/methods , Stroke/therapy , Anesthesia, General , Humans , Stents , Treatment Outcome
11.
J Pediatr Urol ; 15(4): 374.e1-374.e5, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31229415

ABSTRACT

BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.


Subject(s)
Attitude of Health Personnel , Child Health , Pediatricians/statistics & numerical data , Physical Examination/statistics & numerical data , Urogenital System/anatomy & histology , Adolescent , Child , Child, Preschool , Cohort Studies , Databases, Factual , Documentation/statistics & numerical data , Genitalia, Male/anatomy & histology , Hospitals, Pediatric , Humans , Incidence , Infant , Male , Outcome Assessment, Health Care , Physical Examination/methods , Practice Patterns, Physicians' , Retrospective Studies , Tertiary Care Centers , United States
12.
Proc Natl Acad Sci U S A ; 116(6): 2130-2137, 2019 02 05.
Article in English | MEDLINE | ID: mdl-30670643

ABSTRACT

Voluntary sustainability standards (VSS) are stakeholder-derived principles with measurable and enforceable criteria to promote sustainable production outcomes. While institutional commitments to use VSS to meet sustainable procurement policies have grown rapidly over the past decade, we still have relatively little understanding of the (i) direct environmental benefits of large-scale VSS adoption; (ii) potential perverse indirect impacts of adoption; and (iii) implementation pathways. Here, we illustrate and address these knowledge gaps using an ecosystem service modeling and scenario analysis of Bonsucro, the leading VSS for sugarcane. We find that global compliance with the Bonsucro environmental standards would reduce current sugarcane production area (-24%), net tonnage (-11%), irrigation water use (-65%), nutrient loading (-34%), and greenhouse gas emissions from cultivation (-51%). Under a scenario of doubled global sugarcane production, Bonsucro adoption would further limit water use and greenhouse gas emissions by preventing sugarcane expansion into water-stressed and high-carbon stock ecosystems. This outcome was achieved via expansion largely on existing agricultural lands. However, displacement of other crops could drive detrimental impacts from indirect land use. We find that over half of the potential direct environmental benefits of Bonsucro standards under the doubling scenario could be achieved by targeting adoption in just 10% of global sugarcane production areas. However, designing policy that generates the most environmentally beneficial Bonsucro adoption pathway requires a better understanding of the economic and social costs of VSS adoption. Finally, we suggest research directions to advance sustainable consumption and production.

13.
Chem Senses ; 43(8): 627-634, 2018 09 22.
Article in English | MEDLINE | ID: mdl-30219913

ABSTRACT

Autism Spectrum Disorders (ASDs) are characterized by atypical sensory functioning in the visual, tactile, and auditory systems. Although less explored, olfactory changes have been reported in ASD patients. To explore these changes on a neural level, 18 adults with ASD and 18 healthy neurotypical controls were examined in a 2-phase study. Participants were first tested for odor threshold and odor identification. Then, (i) structural magnetic resonance (MR) images of the olfactory bulb were acquired, and (ii) a functional MR imaging olfaction study was conducted. ASD patients exhibited decreased function for odor thresholds and odor identification; this was accompanied by a relatively decreased activation in the piriform cortex. In conclusion, these findings suggest, that the known alterations in olfaction in ASD are rooted in the primary olfactory cortex.


Subject(s)
Autistic Disorder/physiopathology , Odorants , Olfactory Cortex/physiopathology , Olfactory Perception/physiology , Adult , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Psychophysics , Sensory Thresholds/physiology
14.
J Orthop Sports Phys Ther ; 48(6): 511, 2018 06.
Article in English | MEDLINE | ID: mdl-29852832

ABSTRACT

A 14-year-old male football player consulted a sports physical therapist 1 week after being kicked in the front part of his left knee as he was trying to recover an onside kick. Because of these findings in a 14-year-old adolescent, a radiological examination was recommended to rule out a tibia eminence or growth-plate fracture. Radiographs revealed a nondisplaced type III Salter-Harris fracture of the lateral tibial plateau. J Orthop Sports Phys Ther 2018;48(6):511. doi:10.2519/jospt.2018.7868.


Subject(s)
Football/injuries , Salter-Harris Fractures/diagnostic imaging , Tibial Fractures/diagnostic imaging , Adolescent , Humans , Male , Radiography
15.
Psychol Bull ; 144(2): 177-197, 2018 02.
Article in English | MEDLINE | ID: mdl-29144145

ABSTRACT

These meta-analyses of 60+ years of social comparison research focused on 2 issues: the choice of a comparison target (selection) and the effects of comparisons on self-evaluations, affect, and so forth (reaction). Selection studies offering 2 options (up or down) showed a strong preference (and no evidence of publication bias) for upward choices when there was no threat; there was no evidence for downward comparison as a dominant choice even when threatened. Selections became less differentiable when a lateral choice was also provided. For reaction studies, contrast was, by far, the dominant response to social comparison, with ability estimates most strongly affected. Moderator analyses, tests and adjustments for publication bias showed that contrast is stronger when the comparison involves varying participants' standing for ability (effect estimates, -0.75 to -0.65) and affect (-0.83 to -0.65). Novel personal attributes were subject to strong contrast for ability (-0.5 to -0.6) and affect (-0.6 to -0.7). Dissimilarity priming was associated with contrast (-0.44 to -0.27; no publication bias), consistent with Mussweiler (2003). Similarity priming provided modest support for Collins (1996) and Mussweiler (2003), with very weak assimilation effects, depending on the publication bias estimator. Studies including control groups indicated effects in response to upward and downward targets were comparable in size and contrastive. Limitations of the literature (e.g., small number of studies including no-comparison control conditions), unresolved issues, and why people choose to compare upward when the most likely result is self-deflating contrast are discussed. (PsycINFO Database Record


Subject(s)
Psychological Theory , Self Concept , Social Perception , Humans
16.
Article in English | MEDLINE | ID: mdl-28735627

ABSTRACT

Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation. As such, IDO-1 has become a target of intense interest for pharmacological inhibition, for the treatment of cancer. We have previously demonstrated that AA and the prostaglandin metabolite, PGD2, repressed the IFNγ mediated activity of IDO-1 in THP-1 cells and human monocytes. In this study, we characterise the structure-function relationship of fatty acids and eicosanoids towards inhibition of IDO-1 activity in THP-1 cells and human monocytes. Using a commercial library of fatty acids, 55% of fatty acids inhibited IDO-1 activity. The activity of individual FAs was affected by chain length, number of double bonds and bond configuration. Interrogation of an AA derived eicosanoid library identified 13 PGs with significant inhibitory activity. A structure-function analysis revealed that the γ position of the cyclopentenone ring, double bond in the α-ß position of the cyclopentenone ring, the presence of multiple OH groups in the side arm and the addition of an ethanolamide group, significantly increased the inhibitory activity of the PGs. Based on this data we have identified the structure of two possible compounds that may be even more potent pharmacological repressors of IDO-1.


Subject(s)
Enzyme Inhibitors/pharmacology , Fatty Acids/pharmacology , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Monocytes/enzymology , Prostaglandin D2/pharmacology , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Interferon-gamma/pharmacology , Monocytes/cytology , Structure-Activity Relationship , THP-1 Cells
17.
Epidemiol Infect ; 145(7): 1409-1417, 2017 05.
Article in English | MEDLINE | ID: mdl-28219463

ABSTRACT

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.


Subject(s)
Methicillin-Resistant Staphylococcus aureus/physiology , Staphylococcal Infections/epidemiology , Adolescent , Adult , Aged , Anti-Bacterial Agents/pharmacology , Child , Child, Preschool , Clindamycin/therapeutic use , Female , Humans , Infant , Infant, Newborn , Male , Methicillin/pharmacology , Middle Aged , Pennsylvania/epidemiology , Prevalence , Prospective Studies , Risk Factors , Staphylococcal Infections/microbiology , Young Adult
18.
S Afr Med J ; 106(10): 1010-1016, 2016 Sep 09.
Article in English | MEDLINE | ID: mdl-27725022

ABSTRACT

BACKGROUND: Prescribing for older patients is a well-recognised problem, and inappropriate items are prescribed frequently. Several tools and criteria are available to promote rational prescribing in older patients. OBJECTIVE: To determine the prevalence of potentially inappropriate prescriptions (PIPs) in older South African patients. METHODS: A retrospective drug utilisation review was conducted using medicine claims data over a 1-year period. Patients aged ≥65 years with at least one paid claim for any medicine item during this period were included. The prevalence of PIPs was identified by applying the 2012-Beers criteria list. RESULTS: A total of 103 420 patients, mean age 74.0 years (standard deviation 6.7), 57.1% female, were included in the analysis. The number of PIPs identified was 562 852 in 71 206 patients (68.9%). The most common medicines inappropriately prescribed were oestrogen (oral and patch formulations only) (12.4%), meloxicam (7.3%), amitriptyline and combinations thereof (6.5%), diclofenac (6.4%), ibuprofen (6.1%), alprazolam (5.3%), meprobamate and combinations thereof (5.0%), sliding-scale insulin (3.3%), amiodarone (3.1%) and doxazosin (2.6%). Medicines were inappropriately prescribed to women statistically significantly more often than to men (1.9:1; p<0.001), although this difference was not of practical significance (Cramér's V=0.06). CONCLUSIONS: Medicine use in older patients must be appropriate and evaluated regularly. According to explicit criteria, PIPs were found to be common in older patients registered on the database. Monitoring of PIPs may increase the quality of prescribing, but explicit criteria cannot substitute for clinical judgement based on the individual patient.

19.
Rhinology ; 54(4): 374-381, 2016 12 01.
Article in English | MEDLINE | ID: mdl-27421303

ABSTRACT

BACKGROUND: Individuals with hyposmia, or the partial loss of smell, represent a large sector (15 %) of the population that is likely to grow with the current aging population; however, our understanding to how hyposmics centrally process odors is still not clear. One popular non-invasive tool for in vivo imaging of biological activity among human brains has been function magnetic resonance imaging (fMRI) which uses blood-oxygenation level dependent (BOLD) signal as an indirect measurement. Therefore, the aim of this study was to understand differences in olfaction processing between patients with hyposmia and healthy controls using functional magnetic resonance imaging (fMRI). METHODOLOGY: Eleven hyposmic and 12 healthy, normosmic subjects were exposed to two different food-related odors (coffee and peach) during a block-designed fMRI session. Additionally, odor perception qualities were rated for each odor throughout the scanning session. RESULTS: The activations of the normosmic group were localized in typical olfactory areas (insula, orbitofrontal cortex [OFC], limbic system and amygdala). The hyposmic group showed similar regions of activation (insula, OFC, limbic system), however, less activation was found in the amygdala, left anterior cingulate and right OFC, but higher activation was shown in the right parahippocampal and both the left and right posterior cingulate gyrus which are assumed to play an important role in the processing and remembrance of memories. CONCLUSIONS: These results indicate similar central olfactory processing among groups, yet subjects with partial loss may attempt to compensate smell impairment with odor memory or higher motivation to smell.


Subject(s)
Brain/physiopathology , Olfaction Disorders/physiopathology , Adult , Aged , Amygdala/diagnostic imaging , Amygdala/physiopathology , Brain/diagnostic imaging , Case-Control Studies , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiopathology , Female , Functional Neuroimaging , Healthy Volunteers , Humans , Limbic System/diagnostic imaging , Limbic System/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Olfaction Disorders/diagnostic imaging , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology
20.
Br J Anaesth ; 117(1): 87-94, 2016 07.
Article in English | MEDLINE | ID: mdl-27317707

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) can have devastating consequences for children who undergo spinal instrumentation. Prospective evaluations of prophylactic cefazolin in this population are limited. The purpose of this study was to describe the pharmacokinetics and skeletal muscle disposition of prophylactic cefazolin in a paediatric population undergoing complex spinal surgery. METHODS: This prospective pharmacokinetic study included 17 children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, with a median age of 13.8 [interquartile range (IQR) 13.4-15.4] yr and a median weight of 60.6 (IQR 50.8-66.0) kg. A dosing strategy consistent with published guidelines was used. Serial plasma and skeletal muscle microdialysis samples were obtained during the operative procedure and unbound cefazolin concentrations measured. Non-compartmental pharmacokinetic analyses were performed. The amount of time that the concentration of unbound cefazolin exceeded the minimal inhibitory concentration for bacterial growth for selected SSI pathogens was calculated. RESULTS: Skeletal muscle concentrations peaked at a median of 37.6 (IQR 26.8-40.0) µg ml(-1) within 30-60 min after the first cefazolin 30 mg kg(-1) dose. For patients who received a second 30 mg kg(-1) dose, the peak concentrations reached a median of 40.5 (IQR 30.8-45.7) µg ml(-1) within 30-60 min. The target cefazolin concentrations for SSI prophylaxis for meticillin-sensitive Staphylococcus aureus (MSSA) and Gram-negative pathogens were exceeded in skeletal muscle 98.9 and 58.3% of the intraoperative time, respectively. CONCLUSIONS: For children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, the cefazolin dosing strategy used in this study resulted in skeletal muscle concentrations that were likely not to be effective for intraoperative SSI prophylaxis against Gram-negative pathogens.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefazolin/pharmacokinetics , Muscle, Skeletal/metabolism , Scoliosis/surgery , Spinal Fusion , Surgical Wound Infection/prevention & control , Adolescent , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/metabolism , Cefazolin/blood , Cefazolin/metabolism , Female , Humans , Male , Pediatrics , Prospective Studies
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