Prescribing and Consumption of Opioids After Primary, Unilateral Total Hip and Knee Arthroplasty in Opioid-Naive Patients.

BACKGROUND: This cohort study was designed to determine the discrepancy between the quantity of opioid prescribed vs that which was consumed after total knee arthroplasty (TKA) and total hip arthroplasty (THA) in opioid-naive patients. METHODS: Seven hundred twenty-three opioid-naive patients (426 TKAs and 297 THAs) from 7 hospitals in Michigan were contacted within 3 months of their surgery. Opioid prescribing and self-reported consumption was calculated in oral morphine equivalents (OMEs). Secondary outcomes included opioid refill in the first 90 days, pain in the first 7 days post-operatively, and satisfaction with pain care. RESULTS: For TKA, the mean prescribing was 632 mg OME (±229), and the mean consumption was 416 mg (±279). For THA, the mean prescribing was 584 mg OME (±335), and the mean consumption was 285 mg (±301). There were no associations between the amount of opioid prescribed and the likelihood of refill, post-operative pain, or satisfaction with pain control. The amount of opioid prescribed was associated with increased consumption, such that each increase of 1 pill was associated with approximately an additional half pill consumed after adjusting for other covariates. Moreover, 48.2% felt that they received "More" or "Much more" opioid than they needed. CONCLUSION: We recommend no more than 50 tablets of 5 mg oxycodone or its equivalent after TKA and 30 tablets after THA. Although dose reductions in other surgeries have not resulted in harm, continued assessment is needed to ensure that there are no unintended effects of opioid reduction, including worsened pain, decreased satisfaction, emergency department visits, or hospital readmissions. LEVEL OF EVIDENCE: Level III; Retrospective, cohort study.

Verification by the FISH translocation assay of historic doses to Mayak workers from external gamma radiation.

The aim of this study was to apply the fluorescence in situ hybridization (FISH) translocation assay in combination with chromosome painting of peripheral blood lymphocytes for retrospective biological dosimetry of Mayak nuclear power plant workers exposed chronically to external gamma radiation. These data were compared with physical dose estimates based on monitoring with badge dosimeters throughout each person's working life. Chromosome translocation yields for 94 workers of the Mayak production association were measured in three laboratories: Southern Urals Biophysics Institute, Leiden University Medical Center and the former Health Protection Agency of the UK (hereinafter Public Health England). The results of the study demonstrated that the FISH-based translocation assay in workers with prolonged (chronic) occupational gamma-ray exposure was a reliable biological dosimeter even many years after radiation exposure. Cytogenetic estimates of red bone marrow doses from external gamma rays were reasonably consistent with dose measurements based on film badge readings successfully validated in dosimetry system "Doses-2005" by FISH, within the bounds of the associated uncertainties.

Hepatitis A outbreak in Australia linked to imported Medjool dates, June-September 2021.

Abstract: Imported, minimally processed food products have been historically associated with several hepatitis A outbreaks in Australia. Here, we report the first known hepatitis A outbreak in Australia linked to consumption of imported fresh Medjool dates. Between June and September 2021, six genetically identical hepatitis A cases were notified in New South Wales and the Australian Capital Territory. All cases reported date consumption during their exposure period. The implicated dates were positive for hepatitis A virus (HAV) by reverse transcription polymerase chain reaction. Rapid detection of this outbreak and the swift implementation of control measures was facilitated by two key factors. Firstly, Australian international border closures implemented in response to the COVID-19 pandemic meant that a common locally-acquired, as opposed to travel-acquired, source for cases was strongly suspected. Secondly, prompt awareness of a hepatitis A outbreak in the United Kingdom (which was found to be associated with date consumption) allowed for early hypothesis generation and investigation. This paper details the epidemiological and microbiological factors involved in this outbreak investigation and the actions taken to mitigate public health risk.

Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies.

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.

Four recent ciguatera fish poisoning incidents in New South Wales, Australia linked to imported fish

Between 2015 and 2017, the NSW Food Authority investigated 4 ciguatera fish poisoning incidents linked to fish caught in tropical Australian and international waters and imported to New South Wales. Three of the implicated fish were caught near the Capel Bank Seamount, part of the Lord Howe Island Seamount Chain off the coast of Queensland. The fourth incident, in 2017, involved a fish caught between Cooktown and Lizard island, also off the Queensland coast. Thirteen individuals were affected. Early identification of potential Ciguatera fish poisoning (CFP) cases can facilitate a faster incident response, patient diagnosis and treatment. While different fish species were involved, and the severity and duration of symptoms varied between individuals, 3 of the 4 incidents were distinguished by those affected having consumed a fish meal prepared with the head of the fish. Affected individuals also described a sensation of hot/cold temperature reversal or a painful 'sharpness' when in contact with or drinking cold water. This paper outlines a series of incidents where a case's symptoms, which can vary substantially in conjunction with their previous exposure history, the type of fish consumed and how the fish was cooked, can be used to identify potential CFP cases and hence CFP risks that may need to be addressed. Keywords: Ciguatera fish poisoning, ciguatoxins, seafood borne illness, New South Wales, Australia, Pacific ciguatoxin 1-B (P-CTX-1B).

PP2A-B55/SUR-6 collaborates with the nuclear lamina for centrosome separation during mitotic entry.

Across most sexually reproducing animals, centrosomes are provided to the oocyte through fertilization and must be positioned properly to establish the zygotic mitotic spindle. How centrosomes are positioned in space and time through the concerted action of key mitotic entry biochemical regulators, including protein phosphatase 2A (PP2A-B55/SUR-6), biophysical regulators, including dynein, and the nuclear lamina is unclear. Here, we uncover a role for PP2A-B55/SUR-6 in regulating centrosome separation. Mechanistically, PP2A-B55/SUR-6 regulates nuclear size before mitotic entry, in turn affecting nuclear envelope-based dynein density and motor capacity. Computational simulations predicted the requirement of PP2A-B55/SUR-6 regulation of nuclear size and nuclear-envelope dynein density for proper centrosome separation. Conversely, compromising nuclear lamina integrity led to centrosome detachment from the nuclear envelope and migration defects. Removal of PP2A-B55/SUR-6 and the nuclear lamina simultaneously further disrupted centrosome separation, leading to unseparated centrosome pairs dissociated from the nuclear envelope. Taking these combined results into consideration, we propose a model in which centrosomes migrate and are positioned through the concerted action of PP2A-B55/SUR-6-regulated nuclear envelope-based dynein pulling forces and centrosome-nuclear envelope tethering. Our results add critical precision to models of centrosome separation relative to the nucleus during spindle formation in cell division.

Increased frequency of chromosome translocations associated with diagnostic x-ray examinations.

Informative studies of cancer risks associated with medical radiation are difficult to conduct owing to low radiation doses, poor recall of diagnostic X rays, and long intervals before cancers occur. Chromosome aberrations have been associated with increased cancer risk and translocations are a known radiation biomarker. Seventy-nine U.S. radiologic technologists were selected for blood collection, and translocations were enumerated by whole chromosome painting. We developed a dose score to the red bone marrow for medical radiation exposure from X-ray examinations reported by the technologists that they received as patients. Using Poisson regression, we analyzed translocations in relation to the dose scores. Each dose score unit approximated 1 mGy. The estimated mean cumulative red bone marrow radiation dose score was 42 (range 1-265). After adjustment for age, occupational radiation, and radiotherapy for benign conditions, translocation frequencies significantly increased with increasing red bone marrow dose score with an estimate of 0.007 translocations per 100 CEs per score unit (95% CI, 0.002 to 0.013; P = 0.01). Chromosome damage has been linked with elevated cancer risk, and we found that cumulative radiation exposure from medical X-ray examinations was associated with increased numbers of chromosome translocations.

International study of factors affecting human chromosome translocations.

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.

Retrospective biodosimetry among United States radiologic technologists.

Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses. We assessed translocation frequencies in a subset of U.S. radiologic technologists to substantiate ionizing radiation dose estimates developed for 110,418 technologists who worked between 1916 and 1984. From 3,441 cohort members known to have begun working before 1950, we selected a sample of 152, stratified by estimated cumulative dose, over-sampling from higher-dose categories and excluding persons with a prior cancer diagnosis, a personal or family history of chromosomal instability disorders, or a current history of smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than 30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ hybridization (FISH) whole chromosome painting by simultaneously labeling chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE) per person. Linear Poisson regression models with allowance for overdispersion were used to assess the relationship between estimated occupational red bone marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender and estimated red bone marrow absorbed dose score from personal diagnostic procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone marrow dose (95% CI: -0.01, 0.2; P = 0.07), which is similar to the expected estimate based on previous cytogenetic studies (0.05 excess translocations per 100 CE per cGy). Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists.

Presenting statistical uncertainty on cytogenetic dose estimates.

Cytogenetic dosimetry results are customarily accompanied by 95% confidence limits and the derivation of these limits is discussed. Simply presenting values of the best estimate of dose and 95% limits assumes that recipients of dosimetry reports, possibly the patients themselves, have a sufficient grasp of statistics to comprehend the concept of uncertainty. Two further methods have been developed to aid improved understanding for the lay person. The first method, particularly useful for suspected low doses, presents a simple odds ratio indicating that the results favour either zero dose or that suspected; for example, from an unexpected dose recorded on a badge. The second method, described fully here for the first time, uses a graphical illustration of a normalised distribution of dose so that one may visualise the area beneath a curve that represents the probability that the dose lies within various bounds.

CABAS: a freely available PC program for fitting calibration curves in chromosome aberration dosimetry.

The aim of biological dosimetry is to estimate the dose and the associated uncertainty to which an accident victim was exposed. This process requires the use of the maximum-likelihood method for fitting a calibration curve, a procedure that is not implemented in most statistical computer programs. Several laboratories have produced their own programs, but these are frequently not user-friendly and not available to outside users. We developed a software for fitting a linear-quadratic dose-response relationship by the method of maximum-likelihood and for estimating a dose from the number of aberrations observed. The program called as CABAS consists of the main curve-fitting and dose estimating module and modules for calculating the dose in cases of partial body exposure, for estimating the minimum number of cells necessary to detect a given dose of radiation and for calculating the dose in the case of a protracted exposure. The program is freely available at http://www.pu.kielce.pl/ibiol/cabas.

Management of Ciguatoxin Risk in Eastern Australia.

Between 2014 and 2016, five cases of ciguatera fish poisoning (CFP), involving twenty four individuals, were linked to Spanish Mackerel (Scomberomorus commerson) caught in the coastal waters of the state of New South Wales (NSW) on the east coast of Australia. Previously, documented cases of CFP in NSW were few, and primarily linked to fish imported from other regions. Since 2015, thirteen individuals were affected across four additional CFP cases in NSW, linked to fish imported from tropical locations. The apparent increase in CFP in NSW from locally sourced catch, combined with the risk of CFP from imported fish, has highlighted several considerations that should be incorporated into risk management strategies to minimize CFP exposure for seafood consumers.

Adenoma multiplicity in irradiated Apc(Min) mice is modified by chromosome 16 segments from BALB/c.

Ionizing radiation (IR) is a well-characterized carcinogen in humans and mice. The BALB/c mouse strain is unusually sensitive to IR-induced tissue damage and cancer development in a range of organs, suggestive of a partial defect in DNA damage response. This has been confirmed by finding BALB/c-specific functional polymorphism in Prkdc, a gene on mouse chromosome 16 that encodes the catalytic subunit of DNA-dependent protein kinase. Prkdc(BALB) has been associated with increased susceptibility to IR-induced mammary and lymphatic neoplasia. Here, we provide evidence that chromosome 16 segments from BALB/c interact with Apc(Min) (multiple intestinal neoplasia) and specifically enhance IR-induced adenoma development in the upper part of the small intestine.

TT-TG vs. modified lateral patellar edge for determination of tibial tubercle transfer distance in Fulkerson osteotomy procedures.

BACKGROUND: Tibial tubercle-trochlear groove (TT-TG) distance is currently used at our institution to determine tibial tubercle medialization required in Fulkerson osteotomies. If the correlation between a modified lateral patellar edge (LPE) and the transfer distance was found to be stronger than its correlation with TT-TG, it would suggest that the best measurement to use is actually modified LPE. METHODS: The electronic medical records of 32 patients who underwent Fulkerson osteotomy procedures with femoral nerve stimulation were reviewed and measured. For each patient, modified LPE was measured on quadriceps active hyperextension MRI, and TT-TG was measured on passive extension MRI. Correlation between both TT-TG and LPE and tibial tubercle transfer distance was then determined and analysed. RESULTS: The correlation between TT-TG and actual intra-operative tibial tubercle transfer distance in Fulkerson osteotomy procedures with intra-operative femoral nerve stimulation was found to be weak at 0.436 (p<0.05). The correlation between modified LPE and actual intra-operative tibial tubercle transfer distance was found to be strong at 0.697 (p<0.001). CONCLUSIONS: The correlation between modified LPE and actual intra-operative tibial tubercle transfer distance was stronger than the correlation between TT-TG and tibial tubercle transfer distance. This suggests that the modified LPE may actually be a better preoperative determinant than the currently-utilized TT-TG of the transfer distance required during Fulkerson osteotomy procedures. LEVEL OF EVIDENCE: Level II, diagnostic study.

Direct single gene mutational events account for radiation-induced intestinal adenoma yields in Apc(Min/+) mice.

Data on the induction of small intestinal tumors, predominantly adenomas, by X radiation in Apc(Min/+) mice are reported. Comparison of these incidences with estimates of radiation-induced direct single gene mutation frequencies taken from the literature support the hypothesis that direct mutational loss of Apc+ is the sole requirement for initiation of adenoma. Furthermore, estimates of radiation-induced initiation of adenoma per target stem cell in this animal model are similar to or less than radiation-induced direct somatic gene mutation frequencies. Therefore, while the data reported here do not preclude a role for genomic instability in tumor progression, it is not necessary in this model to postulate the involvement of radiation-induced transmissible genomic instability in initiation of intestinal adenoma.

The effect of 4% sodium cromoglicate cutaneous emulsion compared to vehicle in atopic dermatitis in children--A meta-analysis of total SCORAD scores.

An emulsion containing 4% sodium cromoglicate (4% SCG emulsion) has been developed for the treatment of atopic dermatitis in children. We have conducted a meta-analysis of the primary outcome measure (the change in SCORAD score) used in randomized clinical trials (RCTs) with this product. We conducted a search of standard using the keywords, sodium cromoglicate, cromolyn sodium, topical, atopic dermatitis, clinical trial. We identified 19 clinical studies of which 3 used this 4% SCG emulsion formulation, one was a RCT using the change in SCORAD score. We were given access to two further unpublished RCTs, with this measure. The RCTs included 490 subjects (mean age 5.3 years). Each RCT was multicentre of 12 weeks duration, comparing 4% SCG emulsion with the vehicle in which the SCG was dissolved. Using study as the unit and the fixed effect model, the mean difference (95% CI) in the change in SCORAD score was -2.82 (-5.36; -0.29), p = 0.03. Using centre as the unit, and the fixed effect model, the mean difference (95% CI) in the change in SCORAD score was -2.82 (-5.82; -0.46), p = 0.02. These results support the efficacy of this new topical treatment in children with atopic dermatitis.

Long-term use of a 4% sodium cromoglicate cutaneous emulsion in the treatment of moderate to severe atopic dermatitis in children.

INTRODUCTION: Sodium cromoglicate (SCG), a chromone with anti-inflammatory, anti-itch and anti-allergic properties. We report a long-term study of a 4% aqueous solution of SCG in children with moderate to severe atopic dermatitis (AD). MATERIALS AND METHODS: Children aged 1 to 12 years with AD were entered into a 12-week randomised clinical trial (RCT), followed by 12 months open treatment with known 4% SCG emulsion (Altocrom®). Primary endpoint was change in SCORAD score. Secondary endpoints included symptom severity, Quality of Life, concomitant treatment usage, global assessments. RESULTS: One hundred and seventy-seven subjects entered, 118 treated with 4% SCG emulsion and 59 with vehicle: 128 completed 12 months in open study. SCORAD score reduced during RCT by -15.3 (-33%) on 4% SCG emulsion and -18.0 (-39%) on vehicle: p = 0.2331. After 12 months reduction was 56%. No secondary endpoint showed differences between treatments during RCT. Thirty-two subjects reported treatment related events during RCT and open trial. Eleven (7%) reported application site discomfort. Most were reported as mild and most resolved without intervention and the study drug was stopped in one case only. CONCLUSIONS: SCG 4% cutaneous emulsion was well tolerated in children treated for 15 months.

A randomised, controlled trial of a 4% cutaneous emulsion of sodium cromoglicate in treatment of atopic dermatitis in children.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Sodium cromoglicate (SCG) is a chromone with anti-inflammatory, anti-itch and anti-allergic activity. This trial is a 12-week comparison (RCT) of a 4% SCG cutaneous emulsion with its vehicle in AD. MATERIALS AND METHODS: 208 children aged 2-12 years participated, 104 in each group. The primary endpoint was change in SCORAD score. Secondary endpoints included SASSAD score, topical steroid usage and global assessments. RESULTS: SCORAD was reduced by 28% (SCG group) and by 19% (vehicle): difference was statistically significant (p = 0.03) after 8 weeks and nearly significant (p = 0.09) after 12. A similar result occurred in SASSAD (p = 0.001 at 8 weeks). In subjects without major protocol deviations (SCG-64, vehicle-63), difference in SCORAD remained significant at 12 weeks (p = 0.04). Weight of topical steroids reduced in both groups: -0.60 ± 1.3 g/day (35%), SCG and -0.05 ± 1.1 g/day vehicle (p = 0.04). Treatment success, defined as investigator global opinion graded very or moderately effective, was significantly more frequent in SCG group (p = 0.025). Application site discomfort reported by 12.5% of subjects in SCG group and 16.5% in vehicle group. CONCLUSIONS: SCG 4% cutaneous emulsion provides an effective, well-tolerated, steroid-sparing treatment for AD in children.