Occupational Hazards of Orthopedic Surgery Exposures: Infection, Smoke, and Noise.

The orthopedic environment exposes surgeons and staff to infection, surgical smoke, and high levels of noise. It is helpful to understand how exposure increases the risk for adverse health consequences. Protective equipment, safety protocols, and instrument modification can reduce exposure to hazards. When modifications to practice are made, they must be evaluated to ensure they do not introduce new hazards or impede the use of instruments. Despite evidence of risk, protective measures are seldom employed in orthopedic practice. Wider implementation of protection for clinicians may not occur unless the same hazards are shown to impact patient outcomes.

Trends and characteristics in barbiturate deaths Australia 2000-2019: a national retrospective study.

INTRODUCTION: There have been increasing reports documenting barbiturate-related deaths, despite routine prescribing for only relatively rare indications. The aims of the current study were to examine trends in barbiturate-related deaths in Australia from 2000 to 2019 and determine the case characteristics and circumstances of barbiturate-related deaths. METHODS: All barbiturate-related deaths identified in the Australian National Coronial Information System were examined. Information was collected on cause, manner, demographics, location, psychosocial factors, circumstances of deaths and toxicology. We examined these based on the age categories 18-44 years, 45-64 years and ≥65 years. RESULTS: We identified 511 cases. Mean age was 57.9 years (SD 20.2, range 18-100) and 56% were male. Intentional poisoning was the most common cause of death (87.5%) and was slightly higher in the oldest age group (92.1%) and lowest in the youngest age group (81.1%). Pentobarbitone was the most common barbiturate (75.7%) and pentobarbitone-related deaths increased from 0% in 2000 to 93.6% in 2017. There were notable differences between age categories, with the youngest age group recording more severe psychiatric histories. In contrast, the oldest age group were more likely to have severe physical health problems, such as cancer, chronic non-cancer pain, neurological conditions and significant cardiopulmonary morbidity. Euthanasia resources were commonly documented (33.9%), most frequently in the oldest age group (52.3%). CONCLUSION: Barbiturate-related deaths in Australia are increasing, particularly pentobarbitone-related deaths. Most deaths were intentional and involved adults across the lifespan. Younger people were more likely to have significant mental health problems, whilst the oldest age group were more likely to have severe physical health conditions.

A Prospective Study of Cosmetic Outcomes for Patients Treated with Breast Conservation and Radiation Therapy using Shorter Fractionation Schedules at Auckland Hospital, New Zealand.

AIMS: Breast cosmesis is an important outcome for women after breast conservation. It has been shown to be correlated with better patient satisfaction, sexuality and self-esteem. This study reports the subjective and objective breast cosmesis outcomes for women treated at Auckland Hospital Radiation Oncology Department using hypofractionated radiation therapy. MATERIALS AND METHODS: Breast cosmesis was evaluated using a subjective questionnaire and standardised photographs before radiation, at 6 weeks, 1 year, 3 years and 5 years after radiation. Objective evaluation of the photographs and completion of questionnaires were undertaken by clinicians at the same time points. The questionnaire evaluated global cosmesis on a four-point scale - excellent (E), good (G), fair (F) and poor (P). Patient, tumour and treatment factors were evaluated to assess the impact on cosmesis. RESULTS: Three hundred and fifty-eight patients completed the baseline assessments and two hundred and two patients completed the 5-year assessments. Sixty-eight per cent of patients at baseline and 70% at 5 years scored their cosmesis as E/G compared with 52% and 51%, respectively, by clinician assessment. Age >50 years, separation ≤25 cm, non-diabetic, T1 tumours, node negative, quadrant of the scar, no boost and no adjuvant endocrine therapy were correlated with E/G cosmesis. On multivariate analysis at baseline, the individual breast factors that were significantly associated with a score of E/G cosmesis were breast shape (P = 0.028) and scar appearance (P = 0.001). At 5 years, breast shape (P = 0.003), nipple shape (P = 0.019) and scar appearance (P = 0.001) were found to be significant. CONCLUSION: This study shows that most women reported no significant change in their breast cosmesis after hypofractionated radiation treatment over 5 years and that a number of patient, tumour and treatment factors may impact on breast cosmesis.

Echinococcus multilocularis Infection, Southern Ontario, Canada.

Alveolar echinococcosis, the disease caused by infection with the intermediate stage of the Echinococcus multilocularis tapeworm, is typically fatal in humans and dogs when left untreated. Since 2012, alveolar echinococcosis has been diagnosed in 5 dogs, 3 lemurs, and 1 chipmunk in southern Ontario, Canada, a region previously considered free of these tapeworms. Because of human and animal health concerns, we estimated prevalence of infection in wild canids across southern Ontario. During 2015-2017, we collected fecal samples from 460 wild canids (416 coyotes, 44 foxes) during postmortem examination and analyzed them by using a semiautomated magnetic capture probe DNA extraction and real-time PCR method for E. multilocularis DNA. Surprisingly, 23% (95% CI 20%-27%) of samples tested positive. By using a spatial scan test, we identified an infection cluster (relative risk 2.26; p = 0.002) in the western-central region of the province. The cluster encompasses areas of dense human population, suggesting zoonotic transmission.

Echinococcus multilocularis in a wild free-living eastern chipmunk (Tamias striatus) in Southern Ontario: A case report and subsequent field study of wild small mammals.

Southern Ontario has recently been identified as a risk area for Echinococcus multilocularis, based on surveys of foxes (Vulpes vulpes) and coyotes (Canis latrans) which act as definitive hosts of the parasite. In this manuscript, we describe the first detection of E. multilocularis in an eastern chipmunk (Tamias striatus) in North America. This case, submitted to the Canadian Wildlife Health Cooperative (CWHC) in August 2016 as part of ongoing wildlife disease surveillance activities, represents the first report of alveolar echinococcosis in a wild, free living, intermediate host from southern Ontario, providing further evidence of an established sylvatic cycle of E. multilocularis in this region. The finding prompted a field investigation to identify additional cases of alveolar echinococcosis in small mammals in the summer of 2017. Echinococcus multilocularis was not detected in any of the 196 small mammals submitted to the CWHC from across southern Ontario or in any of the 43 small mammals trapped in the area where the infected chipmunk was found. However, given the suspected low prevalence and patchy distribution of E. multilocularis in small mammals, our negative results do not preclude the established presence of the parasite. This case emphasizes the importance of passive surveillance networks for monitoring new and emerging diseases in wildlife populations.

Preventing Hospitalizations From Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Chronic obstructive lung disease is among the leading causes of adult hospital admissions and readmissions in the United States. Preventing acute exacerbations is the primary approach in therapy. Combinations of smoking cessation, pulmonary rehabilitation, vaccinations and inhaled and oral medications may all reduce the overall risk of acute exacerbations. When prevention is unsuccessful, treatment of exacerbations often does not require hospitalization but can be safely executed in the outpatient setting. In the patient who does not require mechanical ventilation or who manifests respiratory acidosis, oxygen supplementation, frequent short-acting inhaled bronchodilators, oral corticosteroids and often antibiotics can abort the decompensation and sometimes return the patient to his or her pre-attack baseline lung function. Several models exist for delivering this care in the ambulatory setting. Follow-up care after an exacerbation has resolved is important, though there are few hard data suggesting which approach is best in this setting.

Association of osteolytic lesions, bone mineral loss and trabecular sclerosis with prevalent vertebral fractures in patients with multiple myeloma.

PURPOSE: In patients with multiple myeloma (MM), computed tomography is widely used for staging and to detect fractures. Detecting patients at severe fracture risk is of utmost importance. However the criteria for impaired stability of vertebral bodies are not yet clearly defined. We investigated the performance of parameters that can be detected by the radiologist for discrimination of patients with and without fractures. METHODS AND MATERIALS: We analyzed 128 whole body low-dose CT of MM patients. In all scans a QCT calibration phantom was integrated into the positioning mat (Image Analysis Phantom(®)). A QCT-software (Structural Insight) performed the volumetric bone mineral density (vBMD) measurements. Description of fracture risk was provided from the clinical radiological report. Suspected progressive disease (PD) was reported by the referring clinicians. Two radiologists that were blinded to study outcome reported on the following parameters based on predefined criteria: reduced radiodensity in the massa lateralis of the os sacrum (RDS), trabecular thickening and sclerosis of three or more vertebrae (TTS), extraosseous MM manifestations (EOM), visible small osteolytic lesions up to a length of 8mm (SO) and osteolytic lesions larger than 8mm (LO). Prevalent vertebral fractures (PVF) were defined by Genant criteria. Age-adjusted standardized odds ratios (sOR) per standard deviation change were derived from logistic regression analysis and area under the curve (AUC) from receiver operating characteristics (ROC) analyses were calculated. ROC curves were compared using the DeLong method. RESULTS: 45% of the 128 patients showed PVF (29 of 75 men, 24 of 53 women). Patients with PVF were not significantly older than patients without fractures (64.6 ± 9.2 vs. 63.3 ± 12.3 years: mean ± SD, p=0.5). The prevalence of each parameter did not differ significantly by sex. Significant fracture discrimination for age adjusted single models was provided by the parameters vBMD (OR 3.5 [1.4-8.8], AUC=0.64 ± 0.14), SO (sOR 1.6[1.1-2.2], AUC=0.63 ± 0.05), LO (sOR 2.1[1.1-4.2] AUC=0.69 ± 0.05) and RDS (sOR 2.6[1.6-4.7], AUC=0.69 ± 0.05). Multivariate models of these four parameters showed a significantly stronger association with the development of PVF (AUC=0.80 ± 0.04) than single variables. TTS showed a significant association with PVF in men(sOR 1.5 [0.8-3.0], AUC=0.63 ± 0.08), but not in women (sOR 2.3[1.4-3.7], AUC=0.70 ± 0.07). PD was significantly associated with PVF in women (sOR 1.9[1.1-3.6], AUC=0.67 ± 0.08) but not in men (sOR 1.4[0.9-2.3], AUC=0.57 ± .07). EOM were not associated with PVF (sOR 1.0[0.4-2.6], AUC=0.51 ± .05). CONCLUSION: In multiple myeloma, focal skeletal changes in low dose CT scans show a significant association with prevalent vertebral fractures. The combination of large osteolytic lesions and loss in radiodensity as can be detected with simple CT Hounsfield measurements of the os sacrum or BMD measurements showed the strongest association to fractures and may be of value for prospective studies.

Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (µCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries.

Acute kidney injury in the cancer patient.

Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.

Mitochondrial DNA deletions and depletion within paraspinal muscles.

AIMS: Although mitochondrial abnormalities have been reported within paraspinal muscles in patients with axial weakness and neuromuscular disease as well as with ageing, the basis of respiratory deficiency in paraspinal muscles is not known. This study aimed to determine the extent and basis of respiratory deficiency in paraspinal muscles from cases undergoing surgery for degenerative spinal disease and post mortem cases without a history of spinal disease, where age-related histopathological changes were previously reported. METHODS: Cervical and lumbar paraspinal muscles were obtained peri-operatively from 13 patients and from six post mortem control cases (age range 18-82 years) without a neurological disease. Sequential COX/SDH (mitochondrial respiratory chain complex IV/complex II) histochemistry was performed to identify respiratory-deficient muscle fibres (lacking complex IV with intact complex II activity). Real-time polymerase chain reaction, long-range polymerase chain reaction and sequencing were used to identify and characterize mitochondrial DNA (mtDNA) deletions and determine mtDNA copy number status. Mitochondrial respiratory chain complex subunits were detected by immunohistochemistry. RESULTS: The density of respiratory-deficient fibres increased with age. On average, 3.96% of fibres in paraspinal muscles were respiratory-deficient (range 0-10.26). Respiratory deficiency in 36.8% of paraspinal muscle fibres was due to clonally expanded mtDNA deletions. MtDNA depletion accounted for further 13.5% of respiratory deficiency. The profile of immunohistochemically detected subunits of complexes was similar in respiratory-deficient fibres with and without mtDNA deletions or mtDNA depletion. CONCLUSIONS: Paraspinal muscles appeared to be particularly susceptible to age-related mitochondrial respiratory chain defects. Clonally expanded mtDNA deletions and focal mtDNA depletion may contribute towards the development of age-related postural abnormalities.

Distraction and interruption in anaesthetic practice.

BACKGROUND: Distractions are a potential threat to patient safety. Previous research has focused on parts of the anaesthetic process but not on entire cases, and has focused on hazards rather than existing defences against error METHODS: We observed anaesthetists at work in the operating theatre and quantified and classified the distracting events occurring. We also conducted semi-structured interviews with consultant anaesthetists to explore existing strategies for managing distractions. RESULTS: We observed 30 entire anaesthetics in a variety of surgical settings, with a total observation time of 31 h 2 min. We noted 424 distracting events. The average frequency of distracting events, per minute, was 0.23 overall, with 0.29 during induction, 0.33 during transfer into theatre, 0.15 during maintenance, and 0.5 during emergence. Ninety-two (22%) events were judged to have a negative effect, and 14 (3.3%) positive. Existing strategies for managing distractions included ignoring inappropriate intrusions or conversation; asking staff with non-urgent matters to return later at a quieter time; preparation and checking of drugs and equipment ahead of time; acting as an example to other staff in timing their own potentially distracting actions; and being aware of one's own emotional and cognitive state. CONCLUSIONS: Distractions are common in anaesthetic practice and managing them is a key professional skill which appears to be part of the tacit knowledge of anaesthesia. Anaesthetists should also bear in mind that the potential for distraction is mutual and reciprocal and their actions can also threaten safety by interrupting other theatre staff.

Randomised, placebo-controlled, crossover trial of sildenafil citrate in the treatment of erectile dysfunction following external beam radiation treatment of prostate cancer.

Erectile dysfunction (ED) commonly affects the quality of life of men after treatment of prostate cancer. We conducted a placebo-controlled, crossover randomised trial to assess the efficacy and tolerability of sildenafil citrate in the treatment of ED developing after external beam radiation treatment (EBRT) of localized prostate cancer. Sixty-six patients who had developed ED following radiation treatment agreed to participate and were allocated to sildenafil or placebo to be taken prior to four sexual attempts. In the crossover period, subjects received the alternative tablet for a further four attempts. Allocation was centrally randomized, and researchers and patients were both blinded to the trial arm. Efficacy was assessed using the International Index of Erectile Function (IIEF) questionnaire and with a separate global efficacy question. Forty-three subjects completed the study. There was a significant increase in mean scores from baseline for all domains of the IIEF with sildenafil compared with placebo (P < 0.001). Affirmative response to the global efficacy question was more common after taking sildenafil compared with placebo. In approximately half of the patients, the improvement in the erectile function domain score corresponded to a moderate improvement in ED (e.g. success 'sometimes' to 'most times'). Sildenafil was associated with mild flushing, nasal stuffiness or indigestion in 8-10% patients and moderate flushing in 10%. The current study adds to the evidence that phosphodiesterase inhibitors are an effective and well-tolerated treatment for ED after EBRT for prostate cancer.

Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells.

Oxidative stress leading to lipid peroxidation is a problem in neurodegenerative diseases, because the brain is rich in polyunsaturated fatty acids and low in endogenous antioxidants. One of the most toxic byproducts of lipid peroxidation, 4-hydroxynonenal (HNE), is implicated in oxidative stress-induced damage in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In this study, the human neuroblastoma cell line SH-SY5Y was used to test the protective effects of increasing the detoxification of HNE by overexpressing the HNE-detoxifying enzyme aldehyde dehydrogenase 1A1 (ALDH1). Overexpression of ALDH1 in the SH-SY5Y cells acts to reduce production of protein-HNE adducts and activation of caspase-3. Our data suggest that detoxification of HNE could be therapeutic in preventing some of the toxic disruptions of the brain's redox systems found in many neurodegenerative diseases.

Minimal-change nephrotic syndrome due to occupational mercury vapor inhalation.

A 25-year-old man developed nephrotic syndrome and severe hypertension following occupational exposure to mercury vapor whilst working at a fluorescent light factory. A renal biopsy confirmed minimal-change disease on light microscopy, immunofluorescence and electron microscopy. He was also noted to be polycythemic which was initially treated with venesection. His blood and urinary mercury levels were elevated and so he was given chelation therapy with 2,3-dimercaptopropane-1-sulfonate (DMPS), along with steroids for his minimal-change disease, resulting in full resolution of his nephrotic syndrome within 6 weeks. He remains well with normal renal function, blood pressure and normal blood and urine mercury concentrations.

Retrospective review of prognostic factors, including 1p19q deletion, in low-grade oligodendrogliomas and a review of recent published works.

The purpose of the present study was to investigate potential prognostic factors in low-grade oligodendrogliomas (LGOs), particularly 1p19q deletion, due to its proven prognostic significance in anaplastic oligodendrogliomas. We carried out a retrospective review of patients with a histological diagnosis of LGO between 1990 and 2000 in Auckland and Wellington, New Zealand. All cases underwent central histopathological review and FISH testing for 1p19q status. Univariate analysis of potential prognostic factors including 1p19q status, age, tumour size, tumour crossing midline, tumour enhancement, extent of surgery and seizures at diagnosis was carried out. Thirty-one patients were eligible and FISH testing was successful in 28 specimens (90%). Twenty-three specimens (82%) had 1p19q deletion; four (14%) had no 1p19q deletion; and one (4%) had 1p deletion alone. At a median follow-up of 87 months (0-147 months), median survival had not been reached and no significant difference in overall survival (OS) based on 1p19q status was detected (1p19q deletion OS 56%; 1p19q intact OS 0%; 1p deletion alone 100% (P = 0.38)). None of the other prognostic factors investigated reached statistical significance. We confirmed the high incidence (82%) of combined 1p19q deletion in LGOs and the feasibility of successful FISH testing in paraffin embedded specimens up to 10-years-old. Analysis of potential prognostic factors was limited by the lack of events during the follow-up period.

Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature.

We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain-selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies.

Signs of irreversible architectural changes occur early in the development of experimental osteoporosis as assessed by in vivo micro-CT.

UNLABELLED: Using in vivo micro-computed tomography, we assessed bone loss in the rat during the first twelve weeks after ovariectomy when structural changes were most rapid. Significant changes to the trabecular architecture were observed, including irreversible changes reflected by reduction in connectivity after only two weeks. This highlights that topological changes to the structure occur early in this experimental model of osteoporosis. INTRODUCTION: The purpose of this study was to establish a longitudinal time course of bone loss in the ovariectomized (OVX) rat model during the initial twelve-week period where structural changes are most rapid, and to identify when irreversible changes occur using in vivo micro-computed tomography (micro-CT). METHODS: The proximal tibiae of OVX (N = 10) and sham (N = 10) operated mature female Wistar rats were micro-CT scanned every two weeks from week 0 to week 12, excluding week 10. Changes in architecture were quantified using direct three-dimensional techniques and serum osteocalcin and CTX-I was measured at weeks 0, 6 and 12. Biomechanical properties were determined from femoral three-point bending and L-4 vertebral compression at the end of the protocol. ANOVA and paired t-tests were used to analyze the longitudinal and endpoint data, respectively. RESULTS: All of the measured architectural parameters changed significantly over the study in the OVX group, including irreversible changes reflected by connectivity density after two weeks. Osteocalcin concentration was elevated in the OVX group. Moderate changes in the mechanical properties of the femora midshaft and vertebrae were observed. CONCLUSIONS: Changes to the bone architecture and mechanics within twelve weeks after OVX highlight the importance of early diagnosis and treatment of osteoporosis.