The Opioid Crisis: Prevalence and Markets of Opioids.

The US opioid crisis came in three waves - prescription opioids, heroin, and illicitly manufactured fentanyls - Centers for Disease Control and Prevention Centers for Disease Control and Prevention resulting in the deaths of nearly 500,000 people from 1996 to 2019. In 2009, drug overdose deaths exceeded those involving automobiles. Opioid overdose deaths contributed to the decrease in life expectancy for Americans from 78.8 to 78.5 during 2014 to 2017. The overprescribing of a schedule II prescription opioid was escalated by pharmaceutical companies promoting a growing belief that pain was an undertreated condition. In 2012, the number of opioid prescriptions peaked at 255 million and deaths exceeded 11,000 per year. The typical prescription opioid abuser was white, male, and 45-55 years of age. The hardest-hit states were in Appalachia and the Northeast. When an abuse-resistant formulation was introduced for OxyContin, the most prevalent prescription opioid, users turned to heroin. From the early 1980s, a new pizza delivery style of Mexican trafficking in black tar heroin infiltrated many of the same states hit hardest by prescription opioids. Heroin overdose deaths reached 14,495 in 2017. As heroin abuse increased in states supplied with black tar heroin, fentanyl-contaminated white powder heroin began to appear in the Northeast. Fentanyl was quickly followed by fentanyl analogs. While heroin deaths continued to escalate through 2017, they were soon overshadowed by fentanyl overdose deaths. Finally, prescription opioid and heroin overdose deaths started to decline in 2017, though fentanyl deaths continued to increase. In late 2019, it appeared that restrictions on transportation and travel due to the COVID-19 pandemic had resulted in decreased availability of illicit drugs, but by 2020 drug abuse had escalated in many countries. Globally, heroin was the primary opioid of abuse and only a few countries - including Canada, Germany, Austria, and Belgium - have experienced a significant increase in prescription opioids. However, illicitly manufactured fentanyls are a growing problem in North America, Europe, Australia, and Asia.

Forensic science educational programs (VI) - Programs in the US.

Historically, academic forensic science (FS) programs in the US tended to be relatively small and were embedded in a criminal justice, chemistry, or biology department. Then, in the early 2000s, interest in FS surged, many colleges and universities responded to student demand by adding FS degrees to their curriculums. The search for forensic science programs in the US was done online, using the American Academy of Forensic Sciences' Forensic Science Education Program Accreditation Commission (FEPAC) list of accredited programs, the CollegeSource® Online Google search, Universities.com, and forensicscolleges.com as primary sources. Once a college or university with one or more FS programs was identified, the university's web pages were accessed to confirm that the program was active. The site was searched to find the location, home department, program URL, contract information, degree name, degrees offered, and accrediting body for the institution. For universities and colleges with multiple programs in different departments, each department and its associated degrees is listed separately under the institutions entry. All levels from PhD to certificate programs have been included. However, degrees that offer forensic courses as electives are not included. Only FEPAC is listed for accredited FS programs. Part of FEPAC accreditation is documenting that the institution is accredited by a regional accreditation organization. No attempt has been made to evaluate the quality of the FS programs listed. With the proliferation of FS programs since 2001, it is important for potential students to evaluate a degree program carefully before deciding to enroll.

Towards indirect potable reuse in South East Queensland.

Faced with limited water supply options in the longer term and the worst drought on record in the short term, the Queensland Government is constructing the Western Corridor Recycled Water Project which will supply up to 182 ML/day of purified recycled water for industrial and potable purposes. The project is one of a suite of capital works projects in progress which in the longer term will supply up to 10% of the region's potable water supply.

The use of F-specific coliphages to assess effluent treatment and reuse schemes.

This study reports on the use of naturally occurring F-specific coliphages, as well as spiked MS-2 phage, to evaluate a land-based effluent treatment/reuse system and an effluent irrigation scheme. Both the natural phages and the spiked MS-2 phage indicated that the effluent treatment/reuse system (FILTER - Filtration and Irrigated cropping for Land Treatment and Effluent Reuse) achieved a reduction in phage levels over the treatment system by one to two log10. FILTER reduced natural F-specific phage numbers from around 10(3) to below 10(2) 100-ml(-1) and the spiked phage from 10(5) to around 10(4) 100-ml(-1) (incoming compared with outgoing water). In the effluent irrigation scheme, phage spiked into the holding ponds dropped from 10(6) to 10(2) 100-ml(-1) after 168 h (with no detectable levels of natural F-specific phage being found prior to spiking). Only low levels of the spiked phage (10(2) gm(-1)) could be recovered from soil irrigated with phage-spiked effluent (at 10(6) phage 100 ml(-1)) or from fruits (around 10(2) phage per fruit) that had direct contact with soil which had been freshly irrigated with the same phage-spiked effluent.

Long-term flow rates and biomat zone hydrology in soil columns receiving septic tank effluent.

Soil absorption systems (SAS) are used commonly to treat and disperse septic tank effluent (STE). SAS can hydraulically fail as a result of the low permeable biomat zone that develops on the infiltrative surface. The objectives of this experiment were to compare the hydraulic properties of biomats grown in soils of different textures, to investigate the long-term acceptance rates (LTAR) from prolonged application of STE, and to assess if soils were of major importance in determining LTAR. The STE was applied to repacked sand, Oxisol and Vertisol soil columns over a period of 16 months, at equivalent hydraulic loading rates of 50, 35 and 8L/m(2)/d, respectively. Infiltration rates, soil matric potentials, and biomat hydraulic properties were measured either directly from the soil columns or calculated using established soil physics theory. Biomats 1 to 2 cm thick developed in all soils columns with hydraulic resistances of 27 to 39 d. These biomats reduced a 4 order of magnitude variation in saturated hydraulic conductivity (K(s)) between the soils to a one order of magnitude variation in LTAR. A relationship between biomat resistance and organic loading rate was observed in all soils. Saturated hydraulic conductivity influenced the rate and extent of biomat development. However, once the biomat was established, the LTAR was governed by the resistance of the biomat and the sub-biomat soil unsaturated flow regime induced by the biomat. Results show that whilst initial soil K(s) is likely to be important in the establishment of the biomat zone in a trench, LTAR is determined by the biomat resistance and the unsaturated soil hydraulic conductivity, not the K(s) of a soil. The results call into question the commonly used approach of basing the LTAR, and ultimately trench length in SAS, on the initial K(s) of soils.

Microbiological status of piggery effluent from 13 piggeries in the south east Queensland region of Australia.

AIMS: To assist in the development of safe piggery effluent re-use guidelines by determining the level of selected pathogens and indicator organisms in the effluent ponds of 13 south-east Queensland piggeries. METHODS AND RESULTS: The numbers of thermotolerant coliforms, Campylobacter jejuni/coli, Erysipelothrix rhusiopathiae, Escherichia coli, Salmonella and rotavirus were determined in 29 samples derived from the 13 piggeries. The study demonstrated that the 13 final effluent ponds contained an average of 1.2 x 10(5) colony-forming units (CFU) 100 ml(-1) of thermotolerant coliforms and 1.03 x 10(5) CFU 100 ml(-1) of E. coli. The Campylobacter level varied from none detectable (two of 13 piggeries) to a maximum of 930 most probable number (MPN) 100 ml(-1) (two of 13 piggeries). Salmonella was detected in the final ponds of only four of the 13 piggeries and then only at a low level (highest level being 51 MPN 100 ml(-1)). No rotavirus and no Erysip. rhusiopathiae were detected. The average log10 reductions across the ponding systems to the final irrigation pond were 1.77 for thermotolerant coliforms, 1.71 for E. coli and 1.04 for Campylobacter. CONCLUSIONS: This study has provided a baseline knowledge on the levels of indicator organisms and selected pathogens in piggery effluent. SIGNIFICANCE AND IMPACT OF THE STUDY: The knowledge gained in this study will assist in the development of guidelines to ensure the safe and sustainable re-use of piggery effluent.

The filter system for tertiary treatment of sewage effluent by land application--its performance in a subtropical environment.

FILTER is an innovative, CSIRO developed system for treating effluent using high rate land application and subsequent effluent recapture via a closely spaced, subsurface drainage network. We report on the summer performance of a FILTER system established in a subtropical environment on a relatively impermeable swelling clay soil underlain by a deep regional water table. Using secondary treated sewage effluent, the FILTER system produced effluent of tertiary nutrient standards (< or = 5 mg/L TN; < or = 1 mg/L TP), with salinity levels suitable for subsequent irrigation reuse (EC < or = 2.5 dS/m). Removal of faecal coliforms was considerably less effective. The hydraulic loading rate achieved was about two and a half times large than conventional irrigation demand, but this was associated with high deep percolation losses (c 3 mm/day). Comparisons are made with the original FILTER system developed and tested by Jayawardane et al. in temperate Australia. Suggestions are made for modifications to, and further testing of FILTER in a subtropical environment.

Transcutaneous interruption of ultrasound contrast agents for blood flow evaluation.

RATIONALE AND OBJECTIVES: The ability to create short boluses in targeted arteries with rapid rise times is limited by the transport of bubbles from the venous to arterial portion of the circulation. Acoustic interruption of contrast agent in arteries may create the short boluses necessary for simple wash-in/wash-out measures of blood flow. METHODS: An ultrasound contrast agent was used with spectral Doppler ultrasound to observe contrast interruption in femoral arteries and VX2 carcinoma in a rabbit model. At an upstream location in the femoral artery, single, sinusoidal ultrasound tone bursts at 1.8 MHz with durations of 0.25 to 1 seconds were applied to interrupt the flow of contrast agent injected intravenously. RESULTS: In VX2 carcinoma, bursts as short as 40 cycles produced contrast interruption lasting only one cardiac cycle within the tumor periphery and I(SPPA) <3 W/cm2 produced measurable interruptions. CONCLUSIONS: Acoustic fields applied transcutaneously interrupted flow of contrast agents to form temporally short negative boluses.

Detection of degradation of magnetic resonance (MR) images: comparison of an automated MR image-quality analysis system with trained human observers.

RATIONALE AND OBJECTIVES: The perceived need for magnetic resonance (MR) imaging quality control (QC) is occasionally minimized on the assumption that significant errors will be detected by the users. To evaluate the validity of this assumption, we compared the sensitivity of a test object and automated image analysis system for MR imaging QC with the sensitivity of trained human observers by evaluating images that were intentionally degraded. METHODS: Parameters for imaging the test object and normal human volunteers were set to values that decreased the signal-to-noise ratio (SNR), caused distortion, and increased the slice thickness and separation. RESULTS: The human observers were able to detect a 6-13% reduction in the SNR and distortions of more than 15% in human images. They were unable to identify 40% increases in the slice thickness. Automated analysis of test object images was able to detect all image degradations at the minimum levels applied. CONCLUSION: The poor sensitivity of the human observers indicated that degradation, especially spatial measurements, could be significantly in error before being detected through visual analysis of clinical images. These errors would be detected by automated analysis of the test object used. Further investigation is needed to better define the accuracy with which quantitative image-quality analysis predicts the effects of degraded image quality on the ability of human observers to detect subtle abnormalities in clinical images.

Acoustic generation of intra-arterial contrast boluses.

Microbubbles generated by ultrasonic cavitation in vivo might be useable as flow indicators in some situations instead of injectable contrast agents. Knowledge of those vascular microbubble-generating ultrasonic fields which produce from negligible up to significant damage will help improve guidelines for more effective, safer diagnostic and therapeutic ultrasound. Microbubble boluses have been generated by a 1.8-MHz, focused sound field in the in vivo canine abdominal aorta. Spatial peak acoustic intensities of 19,000 W cm-2 generated microbubble boluses when exposure was longer than 12 ms, whereas intensities greater than 4300 W cm-2 generated a bolus when exposure was for 250 ms. The onset time of these boluses (less than one cardiac cycle) is unachievable with intravenous contrast injection. With optimized waveforms and focusing, acoustic bolus generation may prove to be an effective, minimally invasive method for fast performance of certain selective angiography.

MRI scanner variability studies using a semi-automated analysis system.

Due to the unique design of the Parallel Rod Test Object (PRoTO) and the associated semi-automated analysis program, it was necessary to test it extensively for precision and accuracy, and preliminarily for utility, before its distribution for wider use in MRI system quality control (QC). The test object and analysis program measured the desired quantities reproducibly and they accurately measured predicted changes from intentionally adjusted imaging system parameters, yielding sensitivity of the various test measures to deviation in the system operating parameters. From a single scan of the most recent revision of the test object, multiple quantitative quality control measures were obtained throughout the scanning volume on two MR imaging systems over periods of six and twelve months, respectively. From these and earlier trials, an initial indication was obtained of which performance measures are worth monitoring for QC. This experience suggests that signal-to-noise ratio (SNR) and distortion (including display scale) should be monitored but not necessarily the resolution. The latter was only found to alter at the same time or later than other parameters such as SNR had changed. Slice thickness was found to vary on some units and this measure was also used in normalizing the SNR by voxel volume. SNR, distortion, and resolution measurements using field-echo sequences were less stable than those using spin-echo sequences. Use of this QC program to test a wide variety of image quality measures allowed timely assessment of the long-term variability of the units tested. Long-term variability may become among the most important measures for comparison of system performance and maintenance.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion.

BACKGROUND: This study was conducted to determine the effect of bupropion on the sexual functioning of male and female outpatients who developed anorgasmia or delayed orgasm while receiving fluoxetine treatment for depression. METHOD: Thirty-nine patients who satisfied criteria for participation in the study discontinued fluoxetine treatment and entered a 2-week washout phase followed by an open 8-week bupropion treatment phase. Three parameters of sexual functioning were followed throughout the study: orgasm function, libido, and satisfaction with overall sexual functioning. Depression was also evaluated at each visit. RESULTS: All patients reported orgasm delay and/or failure at the time of fluoxetine discontinuation. Orgasm function, libido, and satisfaction with sexual functioning improved during the 2-week fluoxetine washout period and during the bupropion treatment phase. Ninety-four percent of patients (29/31) had complete or partial resolution of their orgasm dysfunction at the end of bupropion treatment, and 81% of patients (25/31) were "much" or "very much" more satisfied with their overall sexual functioning. Most patients entered the study with decreased libido on fluoxetine. Libido was "much" or "very much" increased for 81% of patients (25/31) at the end of the study. In addition, depression scores on the Hamilton Rating Scale for Depression and Clinical Global Impressions-Severity scale significantly improved during the bupropion treatment phase. Finally, bupropion was well tolerated by most patients. CONCLUSION: Bupropion may be an appropriate antidepressant for patients who develop sexual dysfunction during fluoxetine treatment or for whom sexual dysfunction is a concern.

Double-blind comparison of bupropion and fluoxetine in depressed outpatients.

BACKGROUND: This study was undertaken to compare the efficacy and safety of bupropion and fluoxetine. METHOD: Moderately to severely depressed outpatients who fulfilled the DSM-III-R criteria for nonpsychotic major depressive disorder and had a score of 20 or more on the Hamilton Rating Scale for Depression (21 item) participated in this two-center study. Following a 1-week placebo phase, patients were randomly assigned to receive either bupropion or fluoxetine for 6 weeks of double-blind treatment. Weekly efficacy assessments included Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. Vital signs and adverse experiences were also assessed weekly. RESULTS: A total of 61 patients were randomly assigned to receive bupropion (225-450 mg/day) and 62 were randomly assigned to receive fluoxetine (20-80 mg/day). The mean daily dose at the end of the study was 382 mg/day for the bupropion treatment group and 38 mg/day for the fluoxetine treatment group. There were no statistically significant differences between treatments on any of the efficacy variables. On the basis of a 50% or greater reduction in the HAM-D scores, 63% (N = 37) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were categorized as responders, and on the basis of CGI scores, 68% (N = 40) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were rated as much or very much improved. HAM-A scores decreased by 59% for both treatment groups. The incidence of treatment-emergent adverse events was low with no statistically significant differences between treatments. Twenty-six percent (N = 16) of the bupropion-treated and 29% (N = 18) of the fluoxetine-treated patients prematurely discontinued treatment. CONCLUSION: Both bupropion and fluoxetine demonstrated similar efficacy in relieving depression and accompanying symptoms of anxiety, and both exhibited a similar, favorable safety profile.

Limbic system dysrhythmia: a diagnostic electroencephalogram procedure utilizing procaine activation.

A diagnostic method is presented that makes it possible to distinguish patients who are most likely to show a positive response to treatment with anticonvulsant medication, thereby cutting across many DSM-III-R diagnoses. Patients are evaluated to determine whether they exhibit at least 4 of 12 groups of symptoms, and the local anesthetic procaine is used, along with an electroencephalogram (EEG) to evaluate for omega band activity (30-50 Hz) of at least 50 microvolts or approximately three times baseline values in the anterior temporal leads. This method was studied in 145 patients with varying diagnoses. Eighty-three percent of patients who were symptom- and procaine-positive responded to anticonvulsants. Specific application to patients with attention-deficit hyperactivity disorder, bipolar disorder, and panic disorder is made. This method may provide a basis for identifying subpopulations of anticonvulsant-responsive patients who often are considered treatment-resistant.

Body image of sexually and physically abused children.

Body size perception was measured in 41 children aged 6-10 who had been either sexually or physically abused, or had no history of abuse. Two psychophysical methods were used, including the staircase method and a signal detection method. In the staircase methodology, children adjusted the direction of distortion of their continuously changing body size. In the signal detection method, children made judgments about the presence or absence of size distortion in presented images. Results using the staircase method indicated children overestimated their body sizes, with no differences between abuse conditions, gender, or age. For the signal detection methodology, no difference in ability to detect the presence/absence of size distortion (d') was found between abuse conditions, although females were less accurate than males. All groups were better able to detect distortion when the image was distorted too wide. Measures of response bias (Ln beta) indicated that sexually abused children had a greater bias to report size distortion as present, as compared with the physically abused children.

Bupropion--an antidepressant without sexual pathophysiological action.

Bupropion, a new nontricyclic antidepressant, was administered clinically on an open basis to 40 male outpatients at doses of 300 to 600 mg/day for 4 to 26 months. Of these, 12 patients had no history of sexual dysfunction, whereas 28 patients reported a history of significant sexual dysfunction (impaired libido, partial erection) while receiving tricyclic, monoamine oxidase inhibitor, maprotiline, and trazodone antidepressants. The adverse sexual effects resolved in 24 of the 28 patients (p less than 0.001) when they were transferred to bupropion. Of the four patients who failed to improve sexually on bupropion, two were diabetic and the other two had lifelong impairments in sexual functioning that were probably unrelated to drugs or depression. The 12 patients who had a negative history of sexual dysfunction continued to have normal sexual functioning during bupropion treatment. Based upon bupropion's lack of anticholinergic and antiadrenergic effects and the clinical observations in this study, this antidepressant appears to have a very low propensity for inducing adverse sexual side effects.

Long-term preventive care in depression: the use of bupropion in patients intolerant of other antidepressants.

The safety and efficacy of bupropion in the preventive care of depression was studied in a long-term open trial. Forty patients from an active general psychiatric practice which emphasizes the treatment of affective disorders have been followed for an average of 336 days (range, 44-791) and seen at least monthly for evaluation with the Hamilton Depression Scale, Zung Self-Rating Scales for Depression and Anxiety, Clinical Global Impression Scale and an adverse reaction report form. One third of the patients had received a diagnosis of bipolar disorder and 50% a diagnosis of recurrent major depressive disorder by DSM-III criteria; all patients were intolerant of tricyclic and other antidepressants. Although several patients were not severely depressed when placed on bupropion, there was a significant improvement on the Zung Self-Rating Scales. There was a striking reduction in the frequency and intensity of adverse reactions, particularly anticholinergic effects, appetite and weight gain, and sexual dysfunction, compared to tricyclics. Also, there were no cardiovascular changes and no physical, ECG, EEG, or laboratory evidence of toxicity. Bupropion represents a significant advance in the treatment of depression, particularly for patients who require long-term preventive care and in whom adverse reactions, which might be tolerated in acute treatment, may lead to noncompliance.

Evidence for convertible forms of soluble uterine cyclic nucleotide phosphodiesterase.

The cyclic nucleotide phosphodiesterase (3':5'-cyclic nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) systems of many tissues show multiple physical and kinetic forms. In contrast, the soluble rat uterine phosphodiesterase exists as a single enzyme form with non-linear Lineweaver-Burk kinetics for cyclic AMP (app. Km of approx. 3 and 20 microM) and linear kinetics for cyclic GMP (app. Km of approx. 3 microM) since the two hydrolytic activities are not separated by a variety of techniques. In uterine cytosolic fractions, cyclic AMP is a non-competitive inhibitor of cyclic GMP hydrolysis (Ki approx. 32 microM). Also, cyclic GMP is a non-competitive inhibitor of cyclic AMP hydrolysis (Ki approx 16 microM) at low cyclic GMP/cyclic AMP substrate ratios. However, cyclic GMP acts as a competitive inhibitor of cyclic AMP phosphodiesterase (Ki approx 34 microM) at high cyclic GMP/cyclic AMP substrate ratios. When a single hydrolytic form of uterine phosphodiesterase, separated initially by DEAE anion-exchange chromatography, is treated with trypsin (0.5 microgram/ml for 2 min) and rechromatographed on DEAE-Sephacel, two major forms of phosphodiesterase are revealed. One form elutes at 0.3 M NaOAc- and displays anomalous kinetics for cyclic AMP hydrolysis (app. Km of 2 and 20 microM) and linear kinetics for cyclic GMP (app. Km approx. 5 microM), kinetic profiles which are similar to those of the uterine cytosolic preparations. A second form of phosphodiesterase elutes at 0.6 M NaOAc- and displays a higher apparent affinity for cyclic AMP (app. Km approx. 1.5 mu) without appreciable cyclic GMP hydrolytic activity. These data provide kinetic and structural evidence that uterine phosphodiesterase contains distinct catalytic sites for cyclic AMP and cyclic GMP. Moreover, they provide further documentation that the multiple forms of cyclic nucleotide phosphodiesterase in mammalian tissues may be conversions from a single enzyme species.