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1.
Otolaryngol Head Neck Surg ; 170(2): 359-372, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38013484

ABSTRACT

OBJECTIVE: The aim of this Meta-analysis is to evaluate the impact of different treatment strategies for early postoperative hypoparathyroidism on hypocalcemia-related complications and long-term hypoparathyroidism. DATA SOURCES: Embase.com, MEDLINE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and the top 100 references of Google Scholar were searched to September 20, 2022. REVIEW METHODS: Articles reporting on adult patients who underwent total thyroidectomy which specified a treatment strategy for postthyroidectomy hypoparathyroidism were included. Random effect models were applied to obtain pooled proportions and 95% confidence intervals. Primary outcome was the occurrence of major hypocalcemia-related complications. Secondary outcome was long-term hypoparathyroidism. RESULTS: Sixty-six studies comprising 67 treatment protocols and 51,096 patients were included in this Meta-analysis. In 8 protocols (3806 patients), routine calcium and/or active vitamin D medication was given to all patients directly after thyroidectomy. In 49 protocols (44,012 patients), calcium and/or active vitamin D medication was only given to patients with biochemically proven postthyroidectomy hypoparathyroidism. In 10 protocols (3278 patients), calcium and/or active vitamin D supplementation was only initiated in case of clinical symptoms of hypocalcemia. No patient had a major complication due to postoperative hypocalcemia. The pooled proportion of long-term hypoparathyroidism was 2.4% (95% confidence interval, 1.9-3.0). There was no significant difference in the incidence of long-term hypoparathyroidism between the 3 supplementation groups. CONCLUSIONS: All treatment strategies for postoperative hypocalcemia prevent major complications of hypocalcemia. The early postoperative treatment protocol for postthyroidectomy hypoparathyroidism does not seem to influence recovery of parathyroid function in the long term.


Subject(s)
Hypocalcemia , Hypoparathyroidism , Adult , Humans , Hypocalcemia/drug therapy , Hypocalcemia/etiology , Calcium/therapeutic use , Hypoparathyroidism/etiology , Hypoparathyroidism/prevention & control , Parathyroid Glands , Vitamin D , Thyroidectomy/adverse effects , Postoperative Complications/etiology , Parathyroid Hormone
2.
J Glob Antimicrob Resist ; 28: 53-58, 2022 03.
Article in English | MEDLINE | ID: mdl-34915202

ABSTRACT

OBJECTIVES: Little is known about the benefits of timely switch from intravenous (IV) to oral antibiotic therapy in children. We evaluated the appropriateness of IV-to-oral switch of antibiotic therapy in remote and regional areas of Australia following the implementation of a multifaceted package of interventions. METHODS: The intervention package, including clinician guidelines, medication review stickers, patient information leaflets and educational resources, was implemented in seven facilities in Queensland, Australia. Children with community-acquired pneumonia and skin and soft-tissue infections were switched to oral therapy if they met the required 'IV-to-oral switch' criteria. Data were collected for a 7-month period from May to November for the baseline (2018) and intervention (2019) phases. RESULTS: A total of 357 patients were enrolled in the study, including 178 in the baseline phase and 179 in the intervention phase. The percentage of patients who switched to oral therapy or stopped IV antibiotics, within 24 h of eligibility, increased from 87.6% (156/178) in the baseline phase to 97.2% (174/179) in the intervention phase (P = 0.003). The average number of extra IV days decreased from 0.45 days in the baseline period to 0.18 days in the intervention period (P < 0.001). The median patient length of stay was 2 days for both phases. The only adverse events recorded were line-associated infiltration, with a decrease from 34.3% (61/178) (baseline) to 17.9% (32/179) (intervention) (P < 0.001). CONCLUSION: A multifaceted intervention package to enhance timely IV-to-oral switch of antibiotic therapy for children in remote and regional facilities is effective.


Subject(s)
Antimicrobial Stewardship , Administration, Intravenous , Anti-Bacterial Agents/therapeutic use , Australia , Child , Humans , Queensland
3.
Aust Dent J ; 66 Suppl 1: S37-S41, 2021 03.
Article in English | MEDLINE | ID: mdl-33893647

ABSTRACT

BACKGROUND: Prescribing of antibiotics by dentists for surgical prophylaxis or as an adjunct to managing dental infections is a substantial part of the overall landscape for prescribed antibiotics in health care settings. METHODS: We explored trends in the antibiotic prescribing patterns of Australian dentists over the 12-year period, 2005-2016. We obtained data on dispensed prescriptions of antibiotics from registered dentists subsidized on the Pharmaceutical Benefits Scheme. RESULTS: Australian dentists were responsible for almost 7 million dispensed prescriptions of antibiotics over 12 years; an average of 24 prescriptions per year per dentist. The most commonly prescribed antibiotic was amoxicillin, followed by amoxicillin + clavulanic acid and metronidazole. These top three antibiotics constituted more than 80% of all antibiotics prescribed and their use increased dramatically over time. There was a large increase in the prescribing of broad-spectrum antibiotics over time, most of which occurred from 2011 to 2016. CONCLUSIONS: Excessive prescribing of broad-spectrum antibiotics runs contrary to national antimicrobial stewardship (AMS) initiatives and guidelines. Multifaceted educational strategies are essential to align prescribing with current best practice. High-level evidence to inform clear guidelines on antibiotic prescribing in dental infections, with audit and feedback, should reduce the inappropriate use of antibiotics in dentistry.


Subject(s)
Anti-Bacterial Agents , Antimicrobial Stewardship , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Australia , Humans , Metronidazole/therapeutic use
4.
IEEE Trans Vis Comput Graph ; 27(10): 3851-3866, 2021 10.
Article in English | MEDLINE | ID: mdl-32340951

ABSTRACT

Recent advances in computational and algorithmic power are evolving the field of medical imaging rapidly. In cancer research, many new directions are sought to characterize patients with additional imaging features derived from radiology and pathology images. The emerging field of Computational Pathology targets the high-throughput extraction and analysis of the spatial distribution of cells from digital histopathology images. The associated morphological and architectural features allow researchers to quantify and characterize new imaging biomarkers for cancer diagnosis, prognosis, and treatment decisions. However, while the image feature space grows, exploration and analysis become more difficult and ineffective. There is a need for dedicated interfaces for interactive data manipulation and visual analysis of computational pathology and clinical data. For this purpose, we present IIComPath, a visual analytics approach that enables clinical researchers to formulate hypotheses and create computational pathology pipelines involving cohort construction, spatial analysis of image-derived features, and cohort analysis. We demonstrate our approach through use cases that investigate the prognostic value of current diagnostic features and new computational pathology biomarkers.


Subject(s)
Breast Neoplasms , Image Interpretation, Computer-Assisted/methods , Imaging Genomics/methods , Machine Learning , Algorithms , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Female , Histological Techniques , Humans , Radiography
5.
BMC Fam Pract ; 21(1): 134, 2020 07 08.
Article in English | MEDLINE | ID: mdl-32641063

ABSTRACT

BACKGROUND: Clinicians who work in primary care are potentially the most influential healthcare professionals to address the problem of antibiotic resistance because this is where most antibiotics are prescribed. Despite a number of evidence based interventions targeting the management of community infections, the inappropriate antibiotic prescribing rates remain high. DISCUSSION: The question is how can appropriate prescribing of antibiotics through the use of Antimicrobial Stewardship (AMS) programs be successfully implemented in primary care. We discuss that a top-down approach utilising a combination of strategies to ensure the sustainable implementation and uptake of AMS interventions in the community is necessary to support clinicians and ensure a robust implementation of AMS in primary care. Specifically, we recommend a national accreditation standard linked to the framework of Core Elements of Outpatient Antibiotic Stewardship, supported by resources to fund the implementation of AMS interventions that are connected to quality improvement initiatives. This article debates how this can be achieved. The paper highlights that in order to support the sustainable uptake of AMS programs in primary care, an approach similar to the hospital and post-acute care settings needs to be adopted, utilising a combination of behavioural and regulatory processes supported by sustainable funding. Without these strategies the problem of inappropriate antibiotic prescribing will not be adequately addressed in the community and the successful implementation and uptake of AMS programs will remain a dream.


Subject(s)
Ambulatory Care , Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship , Inappropriate Prescribing/prevention & control , Primary Health Care , Ambulatory Care/economics , Ambulatory Care/legislation & jurisprudence , Antimicrobial Stewardship/methods , Antimicrobial Stewardship/organization & administration , Decision Support Systems, Clinical , Drug Resistance, Microbial , Guideline Adherence , Humans , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Primary Health Care/methods , Primary Health Care/organization & administration , Primary Health Care/standards
6.
BMJ ; 365: l2006, 2019 May 14.
Article in English | MEDLINE | ID: mdl-31088853

ABSTRACT

CLINICAL QUESTION: What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice. CURRENT PRACTICE: Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing. RECOMMENDATION: The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old). HOW THIS GUIDELINE WAS CREATED: A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. THE EVIDENCE: The systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years' follow-up. UNDERSTANDING THE RECOMMENDATION: The panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC (https://app.magicapp.org/) to support shared decisions and adaptation of this guideline.


Subject(s)
Hypothyroidism/drug therapy , Thyroid Hormones/therapeutic use , Adult , Aged , Body Mass Index , Decision Making , Decision Support Techniques , Depression/drug therapy , Depression/etiology , Fatigue/drug therapy , Fatigue/etiology , Female , Humans , Hypothyroidism/blood , Hypothyroidism/complications , Hypothyroidism/diagnosis , Quality of Life , Thyroid Hormones/adverse effects , Thyrotropin/blood , Thyroxine/blood , Uncertainty
7.
BMJ ; 365: [1-9], May 14, 2019.
Article in English | BIGG - GRADE guidelines | ID: biblio-1094958

ABSTRACT

What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice. Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing. The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying tobecome pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or youngadults (such as those ≤30 years old).


Subject(s)
Humans , Adult , Thyroid Hormones/adverse effects , Thyroid Hormones/therapeutic use , Hypothyroidism/complications , Hypothyroidism/diagnosis , Hypothyroidism/prevention & control , Adult
8.
Sci Rep ; 7(1): 11030, 2017 09 08.
Article in English | MEDLINE | ID: mdl-28887473

ABSTRACT

We demonstrate on-chip, differential DNA and RNA extraction from a single cell using a microfluidic chip and a two-stage lysis protocol. This method enables direct use of the whole extract, without additional washing steps, reducing sample loss. Using this method, the tumor driving pathway in individual cells from a colorectal cancer cell line was determined by applying a Bayesian computational pathway model to sequences obtained from the RNA fraction of a single cell and, the mutations driving the pathway were determined by analyzing sequences obtained from the DNA fraction of the same single cell. This combined functional and mutational pathway assessment of a single cell could be of significant value for dissecting cellular heterogeneity in tumors and analyzing single circulating tumor cells.


Subject(s)
DNA/isolation & purification , Gene Regulatory Networks , Microfluidics/methods , RNA/isolation & purification , Single-Cell Analysis/methods , Cell Line, Tumor , Colorectal Neoplasms/pathology , Complex Mixtures/analysis , Complex Mixtures/isolation & purification , DNA/analysis , Humans , RNA/analysis
9.
Br J Surg ; 104(9): 1123-1130, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28656693

ABSTRACT

BACKGROUND: Surgical-site infections (SSIs) increase patient morbidity and costs. The aim was to identify and synthesize all RCTs evaluating the effect of topical antibiotics on SSI in wounds healing by primary intention. METHODS: The search included Ovid MEDLINE, Ovid Embase, the Cochrane Wounds Specialized Register, Central Register of Controlled Trials and EBSCO CINAHL from inception to May 2016. There was no restriction of language, date or setting. Two authors independently selected studies, extracted data and assessed risk of bias. When sufficient numbers of comparable trials were available, data were pooled in meta-analysis. RESULTS: Fourteen RCTs with 6466 participants met the inclusion criteria. Pooling of eight trials (5427 participants) showed that topical antibiotics probably reduced the risk of SSI compared with no topical antibiotic (risk ratio (RR) 0·61, 95 per cent c.i. 0·42 to 0·87; moderate-quality evidence), equating to 20 fewer SSIs per 1000 patients treated. Pooling of three trials (3012 participants) for risk of allergic contact dermatitis found no clear difference between antibiotics and no antibiotic (RR 3·94, 0·46 to 34·00; very low-quality evidence). Pooling of five trials (1299 participants) indicated that topical antibiotics probably reduce the risk of SSI compared with topical antiseptics (RR 0·49, 0·30 to 0·80; moderate-quality evidence); 43 fewer SSIs per 1000 patients treated. Pooling of two trials (541 participants) showed no clear difference in the risk of allergic contact dermatitis with antibiotics or antiseptic agents (RR 0·97, 0·52 to 1·82; very low-quality evidence). CONCLUSION: Topical antibiotics probably prevent SSI compared with no topical antibiotic or antiseptic. No conclusion can be drawn regarding whether they cause allergic contact dermatitis.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Infective Agents, Local/administration & dosage , Surgical Wound Infection/prevention & control , Anti-Bacterial Agents/adverse effects , Anti-Infective Agents, Local/adverse effects , Drug Eruptions/etiology , Humans , Randomized Controlled Trials as Topic , Wound Closure Techniques , Wound Healing/drug effects
10.
Acta Neurol Scand ; 136(2): 155-159, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28093722

ABSTRACT

OBJECTIVE: This study examined the use of triptan derivatives in Australia between 1997 and 2015, based on a national drug reimbursement database, and compared patterns of use with available international data. METHODS: We obtained publically available data on the number of prescriptions for triptans marketed in Australia (sumatriptan, eletriptan, rizatriptan, zolmitriptan, naratriptan). Dispensed use was measured as defined daily dose (DDD per 1000 population per day) for Australia's concessional beneficiaries (low-income earners, people with disabilities, and seniors). RESULTS: Total triptan use increased at an average annual rate of 112% over the 18-year period. Sumatriptan was the preferred triptan throughout (average annual increase 45%). Zolmitriptan and naratriptan use peaked in 2004, then decreased. Rizatriptan and eletriptan became available in 2010. There were 3.2-fold and 5.9-fold annual increases in their use from 2011 to 2105. There was some evidence suggesting that pattern of triptan use in concessional beneficiaries probably reflected pattern of overall triptan use in Australia. CONCLUSIONS: The use of triptan derivatives in Australia per head of population for treating migraine attacks continued to increase over the 18-year period studied, with use of recently introduced derivatives more than substituting for decreased use of older triptans. This suggests that the available treatments of migraine attacks had achieved what were considered less than adequate therapeutic outcomes.


Subject(s)
Drug Utilization/trends , Migraine Disorders/drug therapy , Migraine Disorders/epidemiology , Pharmacoepidemiology/trends , Tryptamines/therapeutic use , Australia/epidemiology , Humans , Pharmacoepidemiology/methods
11.
Bone ; 95: 108-114, 2017 02.
Article in English | MEDLINE | ID: mdl-27845263

ABSTRACT

INTRODUCTION: Peripheral Blood Mononuclear Cells (PBMCs) have been extensively used as a culture model to generate osteoclasts in vitro. The aim of this study was to assess the osteoclastogenic potential of PBMCs derived from post-menopausal women with longstanding osteoporosis and compare this with PBMCs from healthy controls. MATERIAL AND METHODS: We selected from the population-based Rotterdam Study 82 participants of which 43 were diagnosed with osteoporosis (T-score below -2.5 at the lumbar spine) and the presence of at least 1 fracture and 29 healthy controls (T-score above 1; no fracture). PBMCs were differentiated into osteoclasts, and both differentiation capacity and activity were measured. Total RNA was obtained to assess gene expression of osteoclast markers. Deoxypyridinoline (DPD) was measured in plasma as a marker for bone resorption, in vivo. RESULTS: Neither the number of osteoclasts nor cathepsin K (CTSK) and dendritic cell-specific transmembrane protein (TM7SF4) gene expression was significantly different between both groups. There was also no significant difference in resorption pit area and plasma DPD levels. Stratification by fracture type into a group with vertebral, non-vertebral and both vertebral and non-vertebral fractures showed no difference in osteoclast formation or osteoclastic bone resorption. However, plasma DPD, but not the RNA expression markers, was significantly lower in the group of subjects with vertebral fracture group and those with vertebral and non-vertebral fractures compared to the healthy controls. No differences in osteoclastogenesis, osteoclastic resorption and plasma DPD levels were detected also after exclusion of past or present users of bisphosphonates and glucocorticoids. Stratification into high and low DPD levels showed higher osteoclastogenesis and more osteoclastic bone resorption in the high DPD group compared to the low DPD levels within the group of osteoporotic subjects. CONCLUSION: This study showed no difference in PBMC osteoclastogenic capacity and activity between women with and without osteoporosis and at least one previous fracture, who were on average 29.5years after menopause, suggesting that there is no difference in circulating osteoclast precursors. Although we cannot exclude that circulating precursors may behave differently at the bone site, it is possible that long after menopause a more stable phase of bone turnover is reached compared to earlier after the start of menopause in which differences in circulating osteoclast precursors and osteoclastogenic potential are more prominent.


Subject(s)
Leukocytes, Mononuclear/metabolism , Osteoclasts/pathology , Osteogenesis , Osteoporosis/blood , Osteoporosis/pathology , Aged , Bone Resorption/pathology , Case-Control Studies , Cell Differentiation , Female , Humans , Osteoporosis/drug therapy , Osteoporotic Fractures/drug therapy , Osteoporotic Fractures/pathology
12.
Intern Med J ; 46(12): 1386-1391, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27572659

ABSTRACT

BACKGROUND: Tumour necrosis factor-alpha inhibitors (anti-TNFα) and anakinra are monoclonal antibodies against pro-inflammatory cytokines overexpressed in many systemic inflammatory diseases. In Australia, they are registered for the treatment of several rheumatological, gastroenterological and dermatological indications. Despite increasing observational evidence for their use in off-label indications, there is a paucity of outcome research from the Australian hospital sector. AIMS: To describe the off-label use of anti-TNFα and anakinra at a tertiary referral hospital in Queensland, Australia and consideration of a drug register to inform future clinical decision-making. METHODS: We performed an in-depth retrospective chart audit of off-label treatment with anti-TNFα or anakinra at the Royal Brisbane and Women's Hospital from mid-2010 to mid-2014, linking demographic, phenotypic, pathology and outcome data with these drugs. RESULTS: Off-label use was identified in 10 patients. The most frequent indications were sarcoidosis and dermatological conditions. Three patients required sequential therapy with a second anti-TNFα (total responses = 13). Complete response occurred in 46%, partial response in 38% and primary non-response in 8%. Response was unable to be determined in 8%. We recorded 14 adverse events (infections most common). CONCLUSION: This study suggests that anti-TNFα may be beneficial for some off-label indications (e.g. sarcoidosis). However, the observational design of this study (and pre-existing research) limits the ability to infer causality and generalise results. We propose the creation of a mandatory drug register to monitor off-label use. Whilst comparative efficacy cannot be established without a matched placebo arm, a register would enable some reporting on effectiveness in rare diseases and identify infrequent but serious adverse events.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Sarcoidosis/drug therapy , Skin Diseases/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Australia , Clinical Decision-Making , Evidence-Based Medicine , Female , Humans , Male , Off-Label Use , Patient Selection , Retrospective Studies , Sarcoidosis/immunology , Sarcoidosis/pathology , Skin Diseases/immunology , Skin Diseases/pathology , Tertiary Care Centers , Treatment Outcome
13.
Politics Life Sci ; 35(1): 61-73, 2016.
Article in English | MEDLINE | ID: mdl-27378023

ABSTRACT

A high capacity for visual perception distinguishes Homo sapiens from other primates. This human ability to detect social cues and retain visual records of social networks has been tested mostly with static facial images in laboratory settings. However, media consumption has become closely entangled with the way social life is navigated. Therefore, the study reported here tested demographic differences (gender and education) in visual information processing of social and nonsocial objects featured in audiovisual news content. Women recognized (accuracy) and recalled (salience) social images better than men. On the other hand, men were more skilled at recognizing, but not recalling, nonsocial images. Participants with lower educational levels recognized and recalled fewer images than individuals with higher educational levels. Interactions between demographic variables and time suggest that memory records for social images are more stable than those for nonsocial images. Memory may have survival-relevant importance, serving navigational functions that vary across environmental demands, resulting in differences across demographic groups.


Subject(s)
Cognition , Mass Media , Mental Recall , Adult , Educational Status , Facial Recognition , Female , Humans , Interviews as Topic , Male , Middle Aged , Sex Factors
14.
J Clin Pharm Ther ; 41(5): 486-92, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27349795

ABSTRACT

WHAT IS KNOWN AND OBJECTIVES: Adverse clinical outcomes have been associated with cumulative anticholinergic burden (to which low-potency as well as high-potency anticholinergic medicines contribute). The clinical indications for which anticholinergic medicines are prescribed (and thus the 'phenotype' of patients with anticholinergic burden) have not been established. We sought to establish the overall prevalence of prescribing of anticholinergic medicines, the prevalence of prescribing of low-, medium- and high-potency anticholinergic medicines, and the clinical indications for which the medicines were prescribed in an older primary care population. METHODS: This was a cross-sectional analysis of a cohort study of Australian early-career general practitioners' (GPs') clinical consultations - the Registrar Clinical Encounters in Training (ReCEnT) study. In ReCEnT, GPs collect detailed data (including medicines prescribed and their clinical indication) for 60 consecutive patients, on up to three occasions 6 months apart. Anticholinergic medicines were categorized as levels 1 (low-potency) to 3 (high-potency) using the Anticholinergic Drug Scale (ADS). RESULTS: During 2010-2014, 879 early-career GPs (across five of Australia's six states) conducted 20 555 consultations with patients aged 65 years or older, representing 35 506 problems/diagnoses. Anticholinergic medicines were prescribed in 10·4% [95% CIs 9·5-10·5] of consultations. Of the total anticholinergic load of prescribed medicines ('community anticholinergic load') 72·7% [95% CIs 71·0-74·3] was contributed by Level 1 medicines, 0·8% [95% CIs 0·5-1·3] by Level 2 medicines and 26·5% [95% CIs 24·8-28·1] by Level 3 medicines. Cardiac (40·0%), Musculoskeletal (16·9%) and Respiratory (10·6%) were the most common indications associated with Level 1 anticholinergic prescription. For Level 2 and 3 medicines (combined data), Psychological (16·1%), Neurological (16·1%), Musculoskeletal (15·7%) and Urological (11·1%) indications were most common. WHAT IS NEW AND CONCLUSION: Anticholinergic medicines are frequently prescribed in Australian general practice, and the majority of the 'community' anticholinergic burden is contributed by 'low'-anticholinergic potency medicines whose anticholinergic effects may be largely 'invisible' to prescribing GPs. Furthermore, the clinical 'phenotype' of the patient with high anticholinergic burden may be very different to common stereotypes (patients with urological, psychological or neurological problems), potentially making recognition of risk of anticholinergic adverse effects additionally problematic for GPs.


Subject(s)
Cholinergic Antagonists/therapeutic use , Adult , Australia , Cholinergic Antagonists/adverse effects , Cohort Studies , Cross-Sectional Studies , Drug-Related Side Effects and Adverse Reactions/etiology , Family Practice , Female , General Practitioners , Humans , Male , Practice Patterns, Physicians' , Prescription Drugs/adverse effects , Prescription Drugs/therapeutic use , Primary Health Care , Referral and Consultation
15.
Auto Immun Highlights ; 4(3): 69-80, 2013 Dec.
Article in English | MEDLINE | ID: mdl-26000145

ABSTRACT

Maintenance of health and physiological homeostasis is a synergistic process involving tight regulation of proteins, transcription factors and other molecular processes. The immune system consists of innate and adaptive immune cells that are required to sustain immunity. The presence of pathogens and tumour cells activates innate immune cells, in particular Natural Killer (NK) cells. Stochastic expression of NK receptors activates either inhibitory or activating signals and results in cytokine production and activation of pathways that result in apoptosis of target cells. Thus, NK cells are a necessary component of the immunological process and aberrations in their functional processes, including equivocal levels of NK cells and cytotoxic activity pre-empts recurrent viral infections, autoimmune diseases and altered inflammatory responses. NK cells are implicated in a number of diseases including chronic fatigue syndrome (CFS). The purpose of this review is to highlight the different profiles of NK cells reported in CFS patients and to determine the extent of NK immune dysfunction in subtypes of CFS patients based on severity in symptoms.

16.
Bone ; 50(6): 1260-5, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22425693

ABSTRACT

In patients with a carcinoid syndrome and neuroendocrine tumors of the digestive tract (carcinoids), elevated circulating serotonin (5-hydroxytryptamine, 5-HT) levels can be demonstrated. It can be hypothesized that bone metabolism will be affected in these patients, since serotonin receptors are expressed on bone cells and serotonin effects on bone have been demonstrated. However, to date, no data are available on bone metabolism parameters in patients with neuroendocrine tumors of the digestive tract (carcinoids). In the current retrospective study we have measured serum bone formation markers P1CP (pro-collagen type I C-terminal), and osteocalcin, and the bone resorption marker NTx (collagen breakdown product N-terminal), in a group of 61 carcinoid patients with increased circulating serotonin levels as demonstrated by increased excretion of the serotonin breakdown product, 5-hydroxy indole acetic acid (5-HIAA), in the urine (>50 µmol/24 h, so-called "hyper-secretors") and a control group of 23 carcinoid patients, without increased 5-HIAA excretion (so-called non-secretors). The 24-h urinary excretion of 5-HIAA reflects the 24-h production of serotonin. Measurements of markers of bone metabolism were performed in serum samples obtained before the start of medical treatment. The hypersecretor group had on average a 10-fold higher urinary 5-HIAA excretion than the control (non-secretor) group. No significant differences in bone metabolism parameters could be demonstrated between hyper-secretors and controls (non-secretors). Correlation and regression analyses could not demonstrate significant age- and sex-adjusted correlations between urinary 5-HIAA excretion and any of the markers for bone turnover. A limitation is that the exposure time to elevated levels of serotonin is unknown, which might have been too short to induce effects on bone metabolism. Treatment of human pre-osteoblasts SV-HFO with serotonin didn't change alkaline phosphatase activity throughout differentiation as well as mineralization. In conclusion, the current study in a unique group of untreated carcinoid patients could not demonstrate a major role for circulating serotonin in the control of bone metabolism.


Subject(s)
Bone and Bones/metabolism , Hydroxyindoleacetic Acid/urine , Malignant Carcinoid Syndrome/metabolism , Malignant Carcinoid Syndrome/urine , Aged , Alkaline Phosphatase/metabolism , Biomarkers/blood , Biomarkers/metabolism , Biomarkers/urine , Cell Differentiation/drug effects , Cell Line , Female , Humans , Male , Malignant Carcinoid Syndrome/blood , Middle Aged , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Serotonin/blood , Serotonin/pharmacology
17.
Int J Impot Res ; 23(4): 142-5, 2011.
Article in English | MEDLINE | ID: mdl-21633367

ABSTRACT

Peyronie's disease (PD) is known to be associated with Dupuytren's disease (DD) since 1828. The aim of this study was to investigate the coexistence of DD in a consecutive series of patients with PD and their clinical characteristics. From January 1988 to December 2009 all patients, presenting at our outpatient urological clinic, with PD were also examined for DD. The sample consisted of 415 male subjects with PD, 89 (22.1%) also had DD. A total of 28 men (6.7%) reported to have one or more first or second degree relatives with DD.


Subject(s)
Dupuytren Contracture/epidemiology , Penile Induration/epidemiology , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Netherlands/epidemiology
18.
Eur J Appl Physiol ; 111(7): 1307-12, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21140164

ABSTRACT

Growth hormone (GH) is a commonly used drug aimed at improving sport performance. The aim of this study is to evaluate the immunomodulatory effects of short-term administration of recombinant GH (rhGH) in healthy young males. NK cell number, activity and phenotype, T cell number, CD4(+) (Th1/Th2) cytokine production of IL2, IL4, IL6, IL10, TNF-α and IFN-γ and CD4(+)/CD8(+) ratio with particular attention to the possible correlation to IGF-I production were investigated. 30 males (27 ± 9 years) were randomly assigned to placebo (n = 15) or drug (rhGH) 1 mg/day groups (n = 15) with daily injection for 7 days. IGF-I plasma concentration and flow cytometry data were generated at baseline and days 8, 15, 22 and 29 post injection. Data analysis used General Linear Model with repeated measures, Bonferroni correction factor and significance at p ≤ 0.05. Serum IGF-I levels (ng/mL) increased significantly (p ≤ 0.01) on day 8 (0.48 ± 0.78) after injections compared to baseline (0.31 ± 0.07) and days 15 (0.33 ± 0.06), 22 (0.29 ± 0.05) and 29 (0.29 ± 0.06). A significant time effect was noted in IL10 secretion (pg/mL) from day 15 (P = 35.14 ± 19.93, rhGH = 26.63 ± 16.39) to days 22 (P = 61.32 ± 20.41, rhGH = 74.99 ± 46.91) and 29 (P = 101.98 ± 67.25, rhGH = 107.74; ± 122.58). There was no correlation between IGF-I and NK activity, phenotype or number along with T lymphocyte number, CD4(+)/CD8(+) ratio or Th1 and Th2 cytokine production. In conclusion, cytokine secretion spectrum was not affected by short-term rhGH administration in young males.


Subject(s)
Human Growth Hormone/pharmacology , Immune System/drug effects , Recombinant Proteins/pharmacology , Adult , Drug Administration Schedule , Health , Human Growth Hormone/administration & dosage , Humans , Immune System/physiology , Insulin-Like Growth Factor I/analysis , Killer Cells, Natural/cytology , Killer Cells, Natural/drug effects , Lymphocyte Count , Male , Placebos , Recombinant Proteins/administration & dosage , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , Time Factors , Young Adult
19.
J Sex Marital Ther ; 36(2): 109-17, 2010.
Article in English | MEDLINE | ID: mdl-20169491

ABSTRACT

In many cultures, the erect penis has been a symbol of masculine qualities. Because of this symbolism, a penis that is less than average size can cause insecurity or embarrassment. This series reports the authors' 18-year experience in the management of 60 men with a complaint of a small penis. For 44 of these 60 men, counseling was sufficient; the other 16 had surgery, and of these, 9 were satisfied with the result. Despite limitations, the authors conclude that those men who already achieve a penis length of no less than 7.5 cm (2.95 in) in erection, have only limited benefit from penis-enhancing surgery. This particular patient category should therefore be dissuaded from surgery.


Subject(s)
Patient Satisfaction , Penile Diseases/therapy , Penile Erection , Penis/anatomy & histology , Adolescent , Adult , Body Image , Counseling , Humans , Male , Middle Aged , Self Concept , Young Adult
20.
J Sex Marital Ther ; 36(2): 118-23, 2010.
Article in English | MEDLINE | ID: mdl-20169492

ABSTRACT

Penis lengthening pills, stretch apparatus, vacuum pumps, silicone injections, and lengthening and thickening operations are available for men who worry about their penis size. Surgery is thus far the only proven scientific method for penile enlargement. In this article, we consider patient selection, outcome evaluation, and techniques applied. In our view, sexological counseling and detailed explanation of risks and complications are mandatory before any operative intervention.


Subject(s)
Patient Satisfaction , Penile Diseases/surgery , Penis/surgery , Plastic Surgery Procedures/methods , Urologic Surgical Procedures, Male/methods , Humans , Male , Patient Selection , Penile Diseases/drug therapy , Penis/anatomy & histology , Self Concept , Surgical Flaps , Treatment Outcome
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