A Coloured Pen Needle Education System Improves Insulin Site Rotation Habits: Results of a Randomized Study.

INTRODUCTION: Needle reuse and repeated injection of insulin into the same site encourage lipohypertrophy. We explored the potential of coupling a novel pen needle strategy with community pharmacists to improve injection site rotation. METHODS: Between October 2018 and January 2019, adult insulin users with type 1 or 2 diabetes were enrolled by 16 community pharmacists across 7 Canadian provinces and randomized to their usual pen needles (control) or coloured pen needles packaged with education materials in boxes with reminder sound chips (intervention [mCPN]). A total of 203 individuals completed all requirements of the 30-day study. The primary outcome was a composite of the number of zones injected, the use of new injection zones if the number of zones equaled that at baseline, and the change in size of the injection area from baseline. The pharmacists completed two questionnaires, which provided insights into whether study participation elevated their comfort and confidence in providing injection site rotation counselling. RESULTS: Compared to the control group, more participants in the mCPN arm improved their site rotation practices (54.1% vs. 33.7%; P = 0.005), 15 more increased the number of injection zones used (P = 0.03), and there was less needle reuse (25% vs. 12% reduction). The pharmacists reported improved knowledge of the consequences of lipohypertrophy and the proportion who were "very comfortable" with pen needle tip selection and use rose from 31.3% pre-study to 93.8% post-study. CONCLUSION: The coloured pen needles with their education materials are a novel means of encouraging injection site rotation. Community pharmacists represent an untapped resource for improving injection self-care practices.

Understanding the Clinical Profile of Insulin Degludec, the Latest Basal Insulin Approved for Use in Canada: a Narrative Review.

In recent years, the development of basal insulin therapies has focused on insulin analogues that have longer durations of action and more predictable pharmacokinetic/pharmacodynamic (PK/PD) profiles than their human insulin-based predecessors, such as neutral protamine Hagedorn (NPH) insulin. Dosed once-daily, such analogues can provide a more stable glucose-lowering action, which translates clinically into a reduced risk of hypoglycemia. Insulin degludec (degludec) became available in Canada in 2017 and is the first basal insulin analogue to have a half-life exceeding the dosing interval. As well as offering the promise of an exceptionally flat PK/PD profile when at steady state, this characteristic means that insulin degludec can be dosed with some flexibility with regard to time of day and that it need not be taken at the same time each day. However, the approximately 25-h half-life also has some implications concerning dose titration. This article provides an up-to-date review of the study data describing the clinical profile of degludec, and aims to give helpful and practical advice to prescribers about its use. While the clinical benefits of degludec are described, it is also acknowledged that further study is required to better understand how its clinical performance compares with that of insulin glargine 300 units/mL.

Selective monoaminergic and histaminergic circuit dysregulation following long-term HIV-1 protein exposure.

Between 30 and 60% of HIV-seropositive individuals develop symptoms of clinical depression and/or apathy. Dopamine and serotonin are associated with motivational alterations; however, histamine is less well studied. In the present study, we used fast-scan cyclic voltammetry in HIV-1 transgenic (Tg) rats to simultaneously analyze the kinetics of nucleus accumbens dopamine (DA), prefrontal cortical serotonin (5-HT), and hypothalamic histamine (HA). For voltammetry, subjects were 15 HIV-1 Tg (7 male, 8 female) and 20 F344/N (11 male, 9 female) adult rats. Both serotonergic and dopaminergic release and reuptake kinetics were decreased in HIV-1 Tg animals relative to controls. In contrast, rates of histamine release and reuptake increased in HIV-1 Tg rats. Additionally, we used immunohistochemical (IHC) methods to identify histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus. For IHC, subjects were 9 HIV-1 Tg (5 male, 4 female) and 9 F344/N (5 male, 4 female) adult rats. Although the total number of TMN histaminergic cells did not differ between HIV-1 Tg rats and F344/N controls, a significant sex effect was found, with females having an increased number of histaminergic neurons, relative to males. Collectively, these findings illustrate neurochemical alterations that potentially underlie or exacerbate the pathogenesis of clinical depression and/or apathy in HIV-1.

Insulin Matters: A Practical Approach to Basal Insulin Management in Type 2 Diabetes.

It is currently estimated that 11 million Canadians are living with diabetes or prediabetes. Although hyperglycemia is associated with serious complications, it is well established that improved glycemic control reduces the risk of microvascular complications and can also reduce cardiovascular (CV) complications over the long term. The UKPDS and ADVANCE landmark trials have resulted in diabetes guidelines recommending an A1C target of ≤ 7.0% for most patients or a target of ≤ 6.5% to further reduce the risk of nephropathy and retinopathy in those with type 2 diabetes (T2D), if it can be achieved safely. However, half of the people with T2D in Canada are not achieving these glycemic targets, despite advances in diabetes pharmacological management. There are many contributing factors to account for this poor outcome; however, one of the major factors is the delay in treatment advancement, particularly a resistance to insulin initiation and intensification. To simplify the process of initiating and titrating insulin in T2D patients, a group of Canadian experts reviewed the evidence and best clinical practices with the goal of providing guidance and practical recommendations to the diabetes healthcare community at large. This expert panel included general practitioners (GPs), nurses, nurse practitioners, endocrinologists, dieticians, pharmacists, and a psychologist. This article summarizes the panel recommendations.

HIV-1 and cocaine disrupt dopamine reuptake and medium spiny neurons in female rat striatum.

HIV-1 and addictive drugs, such as cocaine (COC), may act in combination to produce serious neurological complications. In the present experiments, striatal brain slices from HIV-1 transgenic (Tg) and F344 control female rats were studied. First, we examined dopamine (DA) reuptake in control, HIV-1, COC-treated (5µM) and HIV-1+COC-treated, striatal slices using fast scan cyclic voltammetry. COC-treated striatal slices from F344 control animals significantly increased DA reuptake time (T80), relative to untreated control slices. In contrast, in HIV-1 Tg striatal slices, DA reuptake time was extended by HIV-1, which was not further altered by COC treatment. Second, analysis of medium spiny neuronal populations from striatal brain slices found that controls treated with cocaine displayed increases in spine length, whereas cocaine treated HIV-1 slices displayed decreased spine length. Taken together, the current study provides evidence for dysfunction of the dopamine transporter (DAT) in mediating DA reuptake in HIV-1 Tg rats and limited responses to acute COC exposure. Collectively, dysfunction of the DAT reuptake and altered dendritic spine morphology of the MSNs, suggest a functional disruption of the dopamine system within the HIV-1 Tg rat.

HIV-1 transgenic female rat: synaptodendritic alterations of medium spiny neurons in the nucleus accumbens.

HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins.

Characteristics of US workers whose blood lead levels trigger the medical removal protection provision, and conformity with biological monitoring requirements, 2003-2005.

BACKGROUND: Workers with blood lead levels (BLL) > or =60 microg/dl (50 microg/dl for construction workers) or with three or more consecutive BLLs over at least 6 months that average 50 microg/dl or greater are required to be removed from work involving lead exposure that exceeds the OSHA action level. This study estimates the proportion of workers with BLLs that trigger the medical removal provision by industry sector, and examines whether workers received appropriate follow-up blood lead testing. METHODS: Three years (2003-2005) of data from the Adult Blood Lead Epidemiology and Surveillance program were analyzed to identify those industries with a high percentage of workers with BLLs that trigger the medical removal provision. Adjusted rate ratios (RR) of adults with such BLLs were estimated by industry sector compared to the battery manufacturing industry using Poisson regression models. RESULTS: Out of 13,724 adults with BLLs > or =25 microg/dl, a total of 533 adults had BLLs that triggered the medical removal provision. RRs of adults with BLLs triggering medical removal were highest for "painting and wall covering contractors" (RR = 22.1) followed by "highway, street and bridge construction" (RR = 14.7), "amusement, gambling, and recreation" (RR = 11.4), and "glass product manufacturing" (RR = 10.1). Overall, 29% of adults with BLLs triggering medical removal received appropriate follow-up blood lead tests and met the eligibility to return to lead work. CONCLUSIONS: These findings suggest that additional efforts are needed to prevent occupational overexposure to lead in adults, and to ensure proper medical management of those workers who meet medical removal criteria.

Adult blood lead epidemiology and surveillance--United States, 1998-2001.

PROBLEM/CONDITION: Elevated blood lead levels (BLLs) in adults can damage the cardiovascular, central nervous, reproductive, hematologic, and renal systems. The majority of cases are workplace-related. U.S. Department of Health and Human Services recommends that BLLs among all adults be reduced to < 25 microg/dL. The highest BLL acceptable by standards of the U.S. Occupational Safety and Health Administration is 40 microg/dL. The mean BLL of adults in the United States is < 3 microg/dL. REPORTING PERIOD: This report covers cases of adults (aged > or = 16 years) with BLLs > or = 25 microg/dL, as reported by 25 states during 1998-2001. DESCRIPTION OF SYSTEM: Since 1987, CDC has sponsored the state-based Adult Blood Lead Epidemiology and Surveillance (ABLES) program to track cases of elevated BLLs and provide intervention consultation and other assistance. Overall ABLES program data were last published in 1999 for the years 1994-1997. This report provides an update with data from 25 states reporting for > or = 2 years during 1998-2001. During that period, the ABLES program funded surveillance in 21 states - Alabama, Arizona, Connecticut, Iowa, Maryland, Massachusetts, Michigan, Minnesota, New Jersey, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Texas, Washington, Wisconsin, and Wyoming. Four additional states - California, Nebraska, New Hampshire, and Utah contributed data without CDC funding. RESULTS: During 1998-2001, the overall program's annual mean state prevalence rate for adults with BLLs > or = 25 microg/dL was 13.4/100,000 employed adults. This compares with 15.2/100,000 for 1994-1997. Yearly rates were 13.8 (1998), 12.9 (1999), 14.3 (2000), and 12.5 (2001). For adults with BLLs > or = 40 microg/dL, the overall program's annual mean state prevalence rare during 1998-2001 was 2.9/ 100,000 employed adults. This compares with 3.9/100,000 for 1994-1997. Yearly rates were 3.3 (1998), 2.5 (1999), 2.9 (2000), and 2.8 (2001). INTERPRETATION: Although certain limitations exist, the overall ABLES data indicate a declining trend in elevated BLLs among employed adults. PUBLIC HEALTH ACTIONS: ABLES-funded states increased from 21 to 35 in 2002, and more detailed reporting requirements were put into effect. These, and other improvements, will enable the ABLES program to work more effectively toward its 2010 target of eliminating all cases of BLLs > or = 25 microg/dL in adults caused by workplace exposures.