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.

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.

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.

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).

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.

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.

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.

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.

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.

Correlation of radiographic patellofemoral indices with tibial tubercle transfer distance in Fulkerson osteotomy procedures.

BACKGROUND: A laterally tracking patella is commonly seen in patients with chronic recurrent lateral patellar dislocations. Clinical appearance of the J-sign occurs when the patella is congruent with the trochlear groove in flexion and moves over the lateral border of the femoral condyle as the lower leg reaches complete extension. A Fulkerson osteotomy procedure corrects this maltracking of the patella by medially transferring the tibial tubercle. There are many radiographic patellofemoral indices that can be used describe this incongruence about the patelloformal joint. The current literature supports the use of the tibial tubercle-trochlear groove (TT-TG) index in determining the appropriate amount medialization of the extensor mechanism. However there is little agreement in how far to transfer the tibial tubercle to best achieve maximum patello-femoral congruency. It is the senior author's belief that lateral patellar edge (LPE) measure on voluntary quadriceps active hyperextension MRI scan has the strongest correlation with final operative tibial tubercle transfer distance needed to achieve maximum patellofemoral congruency. PURPOSE: The purpose of this study was to show that the voluntary quadriceps active hyperextension MRI measurement of lateral patellar edge (LPE) has the strongest correlation with tibial tubercle transfer distance required to achieve maxium patellofemoral congruency intraoperatively in the terminal 30 degrees of active knee extension compared to all other patellofemoral indices measured on axial MRI scans with the knee in voluntary active knee extension to 30 degrees of flexion, passive full extension, and voluntary quadriceps active hyperextension. STUDY DESIGN: Retrospective case series via review of the electronic medical record. METHODS: Forty-three Fulkerson osteotomy patient charts were reviewed retrospectively. Three different pre-operative axial MRI views were then examined and measured for Tibial Tubercle-Trochlear Groove (tt-tg), lateral patellar edge (LPE), bisect offset (BSO), and lateral patellar displacement (LPD). Each patient had three MRIs: one with the knee resting in extension, one in voluntary quadriceps active hyperextension, and one in voluntary quadriceps active 30 degree flexion. Statistics were then calculated using Statistical Package for the Social Sciences (SPSS) (IBM corp). RESULTS: Tibial tubercle transfer distances required to achieve congruency intraoperatively correlated moderately (0.500-0.300) and were statistically significant (alpha .050) for passive extension MRI measurement of TT-TG (Pearson--0.403, alpha 0.010) and LPD (Pearson .362, alpha 0.022); voluntary quadriceps active hyperextension TT-TG (Pearson 0.487, alpha, 0.001); voluntary quadriceps active flexion TT-TG (Pearson .548, alpha< 0.001), LPE (Pearson .332, alpha 0.029), and LPD (Pearson 0.446 alpha .003). CONCLUSION: The hypothesis that voluntary quadriceps active hyperextension MRI LPE measurement best correlated with tibial tubercle transfer distance was incorrect. The data collected showed correlation and statistical significance for voluntary quadriceps active flexion LPE with required tibal tubercle transfer distance (Pearson 0.34, alpha 0.026). The MRI measurement that best correlated with tibial tubercle transfer distance was voluntary quadriceps active flexion measure of TT-TG (Pearson .556, alpha< 0.001).

Functional outcomes of MPFL reconstruction vs. graft tissue placement.

BACKGROUND: The medial patellofemoral ligament (MPFL) is essential for the maintenance of correct biomechanical function of the knee. Reconstruction of the MPFL is commonly used in the restoration of patellofemoral stability after traumatic lateral subluxation of the patella. Although a method to accurately determine the MPFL's insertion point has been described, it remains unclear if anatomic placement of MPFL graft tissue is essential for preservation of knee function after MPFL reconstruction. Thus, the purpose of this study was to determine the importance of anatomic placement of MPFL graft tissue for the preservation of knee function following MPFL reconstruction operations. METHODS: Twenty-seven subjects who underwent MPFL reconstruction operations were retrospectively analyzed. Postoperative radiographs were reviewed. Measurements were taken, and the placement of each patient's MPFL graft tissue was determined to be anatomic or non-anatomic based on radiographic methods previously described in the literature. Each subject's electronic medical record was then reviewed, and clinical data was recorded. Finally, the clinical outcomes of each patient were compared to placement location of the MPFL graft tissue in their procedure. RESULTS: Thirteen patients were found to have anatomic MPFL graft tissue placement, and 14 non-anatomic. A significant post-operative difference was found between groups in the following parameters: WOMAC pain (anatomic mean = 85.71 ± 11.34, non-anatomic mean = 75.00 ± 26.35 p = 0.018), function (anatomic mean = 85.85 ± 9.96, non-anatomic mean = 79.09 ± 24.45, p = 0.017) and in KOOS symptom (anatomic mean = 75.63 ± 11.79, non-anatomic mean = 67.83 ± 22.40, p = 0.024), pain (anatomic mean = 77.54 ± 8.61, non-anatomic mean = 71.39 ± 25.18, p = 0.01), ADL (anatomic mean = 85.85 ± 9.97, non-anatomic mean = 79.09 ± 24.45, p = 0.017) and overall (anatomic mean = 74.61 ± 10.33, non-anatomic mean = 69.41 ± 24.25, p = 0.01) scores. No significant difference was observed for post-op instability (p = 0.290) or apprehension (p = 0.496), improvement in WOMAC or KOOS, 2-week, 6-week, or final 1-year range of motion, WOMAC stiffness, or KOOS sport/recreation or QOL. CONCLUSION: Within the range of graft placement values considered by this study, while no reduction in range of motion was seen, non-anatomic placement of MPFL graft tissue in MPFL reconstruction operations caused increased pain and decreased function, evidenced by post-operative KOOS and WOMAC scores. CLINICAL RELEVANCE: It seems that the pivotal step in MPFL reconstruction operations is ensuring correct patellofemoral tracking via intraoperative electrical femoral nerve stimulation. If this step of the procedure is performed correctly, non-anatomic placement will not limit range of motion, lead to continued apprehension, or affect the overall biomechanical functioning of the knee.

Chromones.

The chromones are a class of chemical compounds characterised by the presence of the structure 5:6 benz-1:4-pyrone in their chemical make-up. The first chromone in clinical use, khellin, was extracted from the seeds of the plant Ammi visnaga, and had been used for centuries as a diuretic and as a smooth muscle relaxant. Its use in bronchial asthma was reported in 1947. In the 1950s, Benger's Laboratories embarked on a research programme to synthesise and develop modifications of khellin for the treatment of asthma. New compounds were screened using animal models to test the ability of the compound to prevent the anaphylactic release of histamine and SRS-A (leukotrienes) from sensitised guinea pig lung, and a human model to check the ability to reduce the bronchoconstriction induced by inhaled antigen bronchial challenge. For initial screening the human work was undertaken by Dr. R.E.C. Altounyan, who suffered from allergic bronchial asthma and was employed by Benger's Laboratories. After 8 years and more than 600 challenges using over 200 compounds, in 1965 Altounyan arrived at disodium cromoglycate (DSCG), the chromone that met the criteria of providing more than 6 h of protection. DSCG is still used today as a mast cell stabiliser.

The value of physical examination in conjunction with a survey for identifying youth pitchers with arm pain.

OBJECTIVE: The purpose of this study is to evaluate the effectiveness of a screening survey in identifying injuries in youth baseball pitchers. It is hypothesized that a standalone survey is unlikely to give a complete picture and that an additional physical examination is necessary to identify all injuries. METHODS: Seventy-seven youth baseball players who pitched in the last 12 months completed the survey. Players underwent physical examination if they reported a history of time-loss injury (16 players) or if they had any current complaints of pain without a history of time-loss injury (22 players). RESULTS: This screening protocol resulted in positive physical examination findings in 37.6% of all 77 players. This included a rate of 56.3% of pitchers with a positive time-loss injury history and 90.9% of pitchers with a negative time-loss injury, but positive complaint of pain. The most common complaint in both groups was elbow tenderness with the most common location being the medial epicondyle. CONCLUSION: While the survey was effective at identifying time-loss injuries, it may neglect more mild injuries, underestimating the percentage of players with pain and positive physical examination findings. The high frequency of positive examination findings in athletes without a history of time-loss injury demands further investigation.

The effects of topical sodium cromoglicate on itch and flare in human skin induced by intradermal histamine: a randomised double-blind vehicle controlled intra-subject design trial.

BACKGROUND: Itch is a prominent feature of many skin diseases, particularly atopic dermatitis and cutaneous mastocytosis. Sodium cromoglicate (SCG), a chromone developed for the treatment of allergic disease has been shown to reduce the severity of itch when applied topically to subjects with atopic dermatitis. The aim of this study was to investigate whether topical sodium cromoglicate can reduce the severity of itch induced by intradermal histamine. METHODS: SCG was introduced into the skin of healthy volunteers both by iontophoresis and by topical application using a new 4% cutaneous emulsion (Altoderm™). The skin was then challenged with intradermal histamine. Measurements were made of severity of itch, size of wheal and flare and change in blood flux RESULTS: SCG significantly reduced the severity of itch (P = 0.0045) and flare (P = 0.0143) when delivered by iontophoresis. SCG 4% cutaneous emulsion significantly reduced severity of itch (P = 0.024) and flare (P = 0.015) in atopic subjects. Trend analysis showed increasing effect on itch with increased concentrations of SCG, which was significant (P = 0.046). There were no effects on wheal or blood flux. CONCLUSIONS: Topically applied SCG, administered in a new cutaneous emulsion base, significantly reduced the itch and flare caused by intradermal histamine. The effect was greatest in atopic subjects and increased with the concentration of SCG in the emulsion. TRIAL REGISTRATION: ISRCTN35671014.

Intestinal tumours induced in Apc(Min/+) mice by X-rays and neutrons.

PURPOSE: To compare the development of intestinal adenomas following neutron and X-ray exposure of Apc(Min/+) mice (Apc - adenomatous polyposis coli; Min - multiple intestinal neoplasia). MATERIALS AND METHODS: Adult mice were exposed to acute doses of X-rays or fission neutrons. Tumour counting was undertaken 200 days later and samples were taken for Loss of Heterozygosity (LOH) analysis. RESULTS: Tumour numbers (adenomas and microadenomas) increased by 1.4-fold, 1.7-fold, 2.7-fold and 9-fold, after 0.5, 1, 2 and 5 Gy X-rays, respectively, and by 2.4-fold and 5.7-fold, after 0.5 and 1 Gy fission neutrons, respectively. LOH analysis of tumours from neutron-exposed mice showed that 63% had lost Apc and 90% (cf. 53% in controls) had lost D18mit84, a marker for Epb4.1l4a/NBL4 (erythrocyte protein band 4.1-like 4a/novel band 4.1-like 4), known to be involved in the Wnt (wingless-related mouse mammary tumour virus integration site) pathway. Some tumours from neutron-exposed mice appeared to have homozygous loss of some chromosomal markers. CONCLUSIONS: X-ray or fission neutron irradiation results in strongly enhanced tumour multiplicities. Comparison of tumour yields indicated a low Relative Biological Effectiveness of around 2-8 for fission neutrons compared with X-rays. LOH in intestinal tumours from neutron-exposed mice appeared to be more complex than previously reported for tumours from X-irradiated mice.

Oral and topical sodium cromoglicate in the treatment of diffuse cutaneous mastocytosis in an infant.

Diffuse cutaneous mastocytosis (DCM) is a rare, severe, variant of cutaneous mastocytosis. The authors report the case of a male infant who developed maculae and maculopapulae on his legs and abdomen when aged 3.5 months, which spread to all body surfaces within weeks. Diagnosis of DCM was made at the age of 6 months when he had developed extensive bullous eruptions, generalised pruritus, flushing and abdominal pain. Treatment was started with oral dimethindine maleate. At the age of 18 months, oral sodium cromoglicate (SCG) was introduced. At the age of 23 months, additional treatment was started with a cutaneous emulsion containing 4% SCG. Continued treatment with oral dimethindine maleate, oral SCG with the dose maintained at 25 mg/kg/day, and SCG 4% cutaneous emulsion applied two to four times daily has resulted in a steady improvement of symptoms and skin appearance.