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Our ageing medical workforce poses many challenges, not the least of which is acknowledging the contributions of ageing practitioners who continue to practise safely and competently while ensuring that those who are incompetent by virtue of impairment are identified, assessed and either rehabilitated or encouraged to retire. Hitherto, there has been little attempt to review approaches to impairment on a national basis in Australia, let alone with a focus on older doctors. Information regarding pathways for dealing with impairment was obtained from the websites and confirmed by representatives of regulatory bodies of every state or territory in Australia. Using a prevention model we outline the current Australian regulatory processes, address some of the barriers and suggest some solutions to dealing with the older impaired doctor. Much of the focus in dealing with the older impaired doctor is tertiary prevention based, that is, reducing the negative influence of established impairment. There is some uniformity in the way that Australian regulatory bodies deal with impairment that espouses the dual goals of protecting the public and rehabilitating the doctor. The approach is typically individualized and multi-levelled, beginning with assessment followed by rehabilitation where appropriate. A range of secondary and primary prevention measures is proposed for dealing with the problem of the older impaired doctor. These include educating the medical community, encouraging early notification and facilitating career planning and timely retirement of older doctors. This will have benefits both in protecting the public as well as preventing an undignified and humiliating end to often-unblemished careers in medicine. [ABSTRACT FROM AUTHOR]

Investigation of a suspected alcohol or drug impaired driving (DUID) case ideally contains several key elements, including a trained officer documenting observations of driving and subject behavior, and collection of a biological specimen for comprehensive toxicology testing. There is currently no common standard of practice among forensic toxicology laboratories in the United States as to which drugs should be tested for, and at what analytical cutoff. Having some uniformity of practice among laboratories would ensure that drugs most frequently associated with driving impairment were consistently evaluated, that appropriate methods were used to screen and confirm the presence of drugs, and that more accurate data were collected on the extent of drug use among drivers. A survey of United States laboratories actively involved in providing analytical support to the Drug Evaluation and Classification Program identified marijuana, benzodiazepines, cocaine, prescription and illicit opiates, muscle relaxants, amphetamines, CNS depressants, and sleep aids used as hypnotics, as being the most frequently encountered drugs in these cases. This manuscript presents recommendations as to what specific members of these drug classes should at a minimum be tested for in the investigation of suspected DUID cases. Additionally we include recommendations for analytical cutoffs for screening and confirmation of drugs in blood and urine. Adopting these guidelines would ensure that the most common drugs would be detected, that laboratories could compare epidemiological findings between jurisdictions, and that aggregate national statistics on alcohol and drug use in drivers involved in fatal injury collisions were representative of the true rates of drug use in the driving population. [ABSTRACT FROM AUTHOR]

Objective To study the effect of matrix metalloproteinase-9 (MMP-9) on ventricular remodeling and involvement of angiotensin II (Ang II). Methods Thirty-six adult male Wistar rats were randomly divided into control (n = 12), MMP-9 (n = 12), and MMP-9 + olmesartan (n = 12) groups. Recombinant MMP-9 (2.1 ng/g) was injected intraperitoneally twice a week. Olmesartan (3 mg/kg) was given by oral gavage once daily. Animals were treated for 4 or 8 weeks. Cardiac function was assessed by echocardiography followed by histological analysis. The messenger RNA (mRNA) and protein levels of MMP-9 in myocardial tissues were analyzed by reverse transcription polymerase chain reaction and Western blotting, respectively. Serum levels of Ang I, II, angiotensin converting enzyme (ACE) and MMP-9 were determined by enzyme-linked immunosorbent assay (ELISA). Results MMP9 administration for 4 or 8 weeks increased mRNA and protein levels of MMP-9 in myocardial tissues, serum levels of MMP-9, Ang I, II and ACE, and left ventricular mass index (LVMI) but decreased collagen volume fraction (CVF) compared with the control group (all P < 0.05). Cardiomyocyte cell size was significantly enlarged and disorganized with cytoplasmic lysis and necrosis in the MMP-9 group. After olmesartan treatment, myocardial MMP-9 mRNA and protein levels, serum levels of MMP-9 and Ang II, and LVMI were lower, and CVF was higher with significant improvement in myocardial morphology and cardiac function (all P <0.05). Conclusion Recombinant MMP-9 treatment induces ventricular remodeling and cardiac dysfunction by up-regulating Ang II. [ABSTRACT FROM AUTHOR]

When approaching a bend in the road, a driver looks across to the inside kerb before turning the steering wheel. Eye movements and steering are tightly linked, with the eyes leading, which means that the oculomotor controller can assist the neural centres controlling steering. This optimum coordination is observed for all drivers; but despite being the preferred solution to the motor-control problem of successfully steering along a winding road, the question remains as to how crucial such coordinated eye and steering movements are for driving performance. Twenty subjects repeatedly drove a simulated stage of the World Rally Championship, aiming to complete the course in the fastest possible time. For the first six repetitions they used the usual coordination of eye movements and steering; for drives 7–12 they were instructed to fixate on a small spot in the centre of the screen (centre gaze). Prevention of coordination in this way impaired their performance (drives 6 and 7 compared), dramatically increasing their time taken to complete the course, equivalent to slipping 19 places down the leader board in the actual rally stage. This indicates that the usual pattern of eye movements correlated with steering is crucial for driving performance. Further experiments are suggested to reveal whether any attentional demand associated with keeping the eyes still contributes to the loss in performance. [ABSTRACT FROM AUTHOR]

Abstract: Background and Objective: To compare clinical profiles and risk of diabetes between subjects with transient (trIGT) and persistent (pIGT) impaired glucose tolerance in Taiwan. Study Design and Setting: In the pIGT group, IGT was diagnosed in two consecutive periods (1992–1994 and 1995–1996); in the trIGT group, the diagnosis was IGT at the baseline but normal glucose tolerance in the second period. The normal group was defined by fasting plasma glucose &#60; 6.1 mmol/L and 2-hour post-load plasma glucose &#60; 7.8 mmol/L in both periods. All three groups were considered eligible subjects for further follow up (1998–1999). Results: Among 298 nondiabetic subjects at baseline, there were 29 new cases of diabetes diagnosed according to 1999 WHO criteria in 1,614.3 person-years of follow-up (1.79%/year; 95% CI=1.14–2.44%/year). Among subjects with normal, trIGT, or pIGT, the incidence rates were 0.73%/year (8/1,093.0; 95% CI=0.22–1.24%/year), 2.57%/year (7/272.2; 95% CI=0.67–4.47%/year), and 5.62%/year (14/249.1; 95% CI=2.68–8.56%/year), respectively. Conclusion: The group with trIGT had abnormal glucose tolerance and β-cell dysfunction, which may represent an earlier stage than the group with pIGT in development of type 2 diabetes. Moreover, pIGT, insulin resistance, and β-cell dysfunction played independent roles in the deterioration from IGT to diabetes. [Copyright &y& Elsevier]

Despite development of many chemotherapeutic regimens, colorectal cancer continues to have a high mortality. One of the major new potential therapies is interleukin-12, a heterodimeric cytokine produced by antigen presenting cells. In vitro and in vivo studies have demonstrated the role of interleukin-12 in stimulating a cell-mediated anti-tumor response against a number of colon adenocarcinoma tumor models. However, it is unknown whether patients with colorectal cancer have impaired interleukin-12 production. A study was performed to investigate production of interleukin-12 preoperatively and the relationship between these levels and disease stage at surgery.Preoperative peripheral blood mononuclear cells from colorectal cancer patients and agematched controls were stimulated by Staphylococcus aureus Cowan's Strain 1 (0.0075 percent wt/vol) in vitro for 24 hours. Expression of interleukin-12 was then assessed by enzyme-linked immunosorbent assay. A single pathologist assessed the tumors for stage according to TNM and Dukes classifications.Twenty-eight patients with colorectal cancer and 14 controls were recruited for the study. Interleukin-12 production was significantly impaired in patients with colorectal cancer compared with controls (P=0.014), especially those with advanced disease: Dukes C, P=0.001 and T4, P<0.05.Interleukin-12 production is impaired in patients with colorectal cancer, especially those with advanced disease, suggesting a defective Th1-mediated anti-tumor response. These patients may well benefit from exogenous interleukin-12 treatment. [ABSTRACT FROM AUTHOR]

Objective To investigate myocardial apoptosis and the expression of apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) and Bax], cardiac hypertrophy, and function in spontaneously hypertensive rats (SHR) during aging. Methods Male SHR (n = 36) and Wistar-Kyoto rats (WKY, n = 30) were monitored for their cardiac function from 14 to 102 weeks of age using echocardiography. Myocardial apoptosis in the subendocardium and subepicardium was analyzed using TUNEL staining. The apoptosis-related proteins (Bcl-2 and Bax) were assessed by Western blot analysis. Results Left ventricular mass index (LVMI) in SHR increased progressively with age. Left ventricular ejection fraction (LVEF) showed no significant difference from 14 to 66 weeks of age, but decreased significantly in SHR from 84 to 102 weeks of age. The apoptotic index (APOI) of myocardial cells in SHR increased with age, in which subendocardial APOI (APOI-endo) increased at 66 weeks and was significantly higher than the age-matched WKY (9.83 ± 3.97 vs. 4.03 ± 2.06, P < 0.05). Additionally, the subepicardial APOI (APOI-epi) increased significantly at 84 weeks of age (P < 0.05). Bax/Bcl-2 ratio was higher in SHR than WKY at 66 weeks (3.98 ± 0.80 vs. 0.29 ± 0.06, P < 0.05), and enhanced further at 102 weeks of age (10.54 ± 1.60 vs. 0.70 ± 0.13, P < 0.05). Myocardial APOI was positively correlated with LVMI (r = 0.83, P < 0.01), negatively with LVEF in 66–102 weeks (r = −0.81, P < 0.01), and positively with Bax/Bcl-2 ratio (r = 0.79, P < 0.01). Conclusion Myocardial apoptosis increases with aging and is associated with progressive left ventricular remodeling and cardiac dysfunction in SHR. [ABSTRACT FROM AUTHOR]

Objectives: Postpartum mothers with gestational diabetes may remain with either type 2 diabetes mellitus, impaired glucose tolerance or impaired fasting glucose. Our aim in this study was to identify maternal variables that could predict 1 or more of these conditions., Methods: In 193 singleton pregnancies with gestational diabetes, we applied bivariate logistic regression and receiver-operating characteristic curves to data from the index glucose-challenge test that allowed the diagnosis of gestational diabetes., Results: Receiver-operating characteristic curves of fasting glucose from the index glucose-challenge test predicted impaired fasting glucose and type 2 diabetes mellitus combined, with a sensitivity of 100%, false-positive rate of 40.5%, area under the curve of 0.849, p=0.004 and positive predictive value 45%, and with a cutoff point of 4.7 mmol/L., Conclusions: At the time of diagnosis of gestational diabetes during pregnancy, a basal glucose level of ≥4.7 mmol/L on index glucose-challenge test indicates a 45% probability of either type 2 diabetes mellitus or impending diabetes early postpartum., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Purpose: Safety data on commonly used herbal medicinal (HM) products (HMPs) and marketed in Ghana are scarce. We assessed the sub-chronic toxicity of three most-patronised commercial antimalarial HMPs in Kumasi, Ghana., Method: Top three HMPs (designated as herbal products 'A' (HPA), 'B' (HPB) and 'C' (HPC)) were selected after a mini-survey and sub-chronic toxicity evaluation conducted in accordance with Organisation for Economic Co-operation and Development (OECD) 407 guidelines. Control rats received clean water while test groups received daily adult human dose (DAHD), 5× DAHD or 10× DAHD of either HPA, HPB or HPC for 30 days. Rats were killed on day 31 to obtain biochemical, haematology and histology samples for analysis. Data were analysed by one-way analysis of variance (ANOVA) and post hoc Tukey's test., Results: The three HMPs produced alterations in liver morphology predominantly characterised by prominent foci of fatty change with scattered hepatocytes containing intracytoplasmic fat globules and congested central veins and sinusoids. The lungs showed alveolar with evidence of inflammation and foci of epithelial sloughing. Alveolar spaces were also obscured by debris and inflammatory cells. HPA and HPC produced scattered intensely congested heart vessels while HPB(10) produced haemorrhage and amorphous exudates within the heart. All HMPs produced neither treatment-related deaths nor significant change in haematological and biochemical parameters, except for HPA and HPB which decreased (P<0.05) aspartate aminotransferase (AST) and HPB, which elevated (P<0.05) fasting blood glucose (FBG)., Conclusion: Data from the present study suggest the potential of the herbal products (HPs), HPA, HPB and HPC, to cause major organ-system dysfunction or damage. We advise cautious use of these products and recommend further safety evaluation in chronic toxicity models., (© 2020 The Author(s).)

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Background Treatment results of small molecule tyrosine kinase inhibitors (TKIs) have been improved, but cancer treatment-related cardiac dysfunction (CTRCD) has become a problem. However, the CTRCD risk of TKIs has not been fully clarified, and monitoring indicators have not been established. Therefore, in order to detect CTRCD early, we aimed to pinpoint the TKIs that needs attention. Method Data from the Japanese Adverse Drug Event Report database from April 2004 through January 2018 was used. In this study, a total of 25 TKIs in monotherapy were studied in principle to avoid the presence of concomitant medication. We examined the relationship between heart failure and TKIs with a reporting odds ratio (ROR) which is a signal detection by data mining Method. The 95% confidence interval lower limit value > 1 was taken as a signal. We also confirmed the target kinase and heart failure alert in the package insert of the TKIs. Result Signals of heart failure were detected in 10 (Alectinib, Axitinib, Bosutinib, Dasatinib, Imatinib, Osimertinib, Pazopanib, Ponatinib, Ruxolitinib and Sunitinib) of the 25 TKIs, and ABL-1, VEGFR and PDGFR were common in the target kinases. Signals were also detected in Alectinib, Bosutinib and Osimertinib, but their package inserts did not alert for heart failure. Death cases were also included in reported heart failure cases. Conclusion Knowledge of the ten TKIs or drugs having ABL-1, VEGFR, PDGFR as the target kinase that signal for a risk of heart failure may lead to the early detection of adverse events by monitoring. There are also serious cases for three drugs for which the risk of heart failure is unknown, so we suggest that it is necessary to conduct periodic monitoring. [ABSTRACT FROM AUTHOR]

Background In the treatment of advanced cancer patients with severe cardiac dysfunction, there is a risk that the side effects of the chemotherapy may lead to a serious situation, and it is necessary to carefully judge the indications. There were only a few reported cases of chemotherapy for such patients. Here we report our experience with a patient who had continued chemotherapy for more than a year and a half for advanced sigmoid colon cancer with severe cardiac dysfunction. Case presentation A 73-year-old man came to our hospital because positive fecal occult blood was pointed out in a medical examination in March 2017. He had been diagnosed dilated cardiomyopathy at the age of sixty, and his LVEF was about 25% by the recent echocardiogram. A colonoscopy was performed in May, sigmoid colon cancer was found, and further CT examination was revealed multiple liver metastases. We determined that surgery was not a possible treatment option for him, and we decided to perform chemotherapy. In June we introduced to the patient S-1 plus oxaliplatin combination therapy. We changed to S-1 plus irinotecan combination therapy because of becoming PD from November in the same year. After that SD was maintained for a while, but it became PD by December 2018, and we changed to FTD/TPI as the third line chemotherapy from January 2019. Discussion Median survival of BSC follow-up for unresectable advanced recurrent colorectal cancer was reported to be 6 to 8 months. This case has survived more than a year and a half after starting chemotherapy, suggesting that chemotherapy should be performed as much as possible even for cancer patients with severe cardiac dysfunction. However, there are few such case reports, and it is necessary to accumulate and study more cases from now on. [ABSTRACT FROM AUTHOR]

Background One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods A search of PubMed and abstracts from key conferences identified randomized trials that compared abbreviated trastuzumab therapy to 1 year of treatment in early-stage HER2-positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted for disease-free survival (DFS) and overall survival (OS). Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor expression, and the duration of abbreviated trastuzumab (9–12 weeks vs 6 months). Odds ratios (ORs) and 95% confidence intervals were computed for prespecified cardiotoxicity events including cardiac dysfunction and congestive heart failure. P values were two-sided. Results Analysis included six trials comprising 11 603 patients. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI = 1.05 to 1.25, P  = .002) and OS (HR = 1.15, 95% CI = 1.02 to 1.29. P  = .02). The effect on DFS was not influenced by estrogen receptor status (P for the subgroup difference = .23), nodal involvement (P  = .44), or the different duration of trastuzumab in the experimental arm (P  = .09). Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI = 0.55 to 0.81, P  < .001) and congestive heart failure (OR = 0.66, 95% CI = 0.50 to 0.86, P  = .003). Conclusions Compared with 1 year, shorter duration of adjuvant trastuzumab is associated with statistically significantly worse DFS and OS despite favorable cardiotoxicity profile. One year of targeted HER2 treatment should remain the standard adjuvant treatment in early-stage HER2-positive disease with appropriate cardiac monitoring. [ABSTRACT FROM AUTHOR]

Background: The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term.Objective: The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between a low cerebroplacental ratio at term, reduced fetal growth velocity, and adverse pregnancy outcome.Study Design: This was a retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within 2 weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in the abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio and the low abdominal circumference growth velocity (in the lowest decile) and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small-for-gestational-age neonates.Results: The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 2.10; 95% confidence interval, 1.71-2.57, P <0.001) and small for gestational age (adjusted odds ratio, 3.60; 95% confidence interval, 3.04-4.25, P < .001). After the exclusion of pregnancies resulting in small-for-gestational-age neonates, a low cerebroplacental ratio multiples of the median remained significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 1.76; 95% confidence interval, 1.34-2.30, P < .001) and birthweight centile (adjusted odds ratio, 0.99; 95% confidence interval, 0.998-0.995, P < .001). The need for operative delivery for fetal compromise was significantly associated with a low cerebroplacental ratio (adjusted odds ratio, 1.40; 95% confidence interval, 1.10-1.78, P = .006), even after adjusting for both the umbilical artery pulsatility index multiples of the median and middle cerebral artery pulsatility index multiples of median. The results were similar, even after the exclusion of pregnancies resulting in small-for-gestational-age neonates (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84, P = .018). Low cerebroplacental ratio multiples of the median remained significantly associated with the risk of operative delivery for presumed fetal compromise (P < .001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted, even after the exclusion of small-for-gestational-age births. In appropriate-for-gestational-age-sized fetuses, abdominal circumference growth velocity was significantly lower in those with a low cerebroplacental ratio multiples of the median than in those with normal cerebroplacental ratio multiples of the median (P < .001).Conclusion: The cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry. [ABSTRACT FROM AUTHOR]