Tenecteplase has been shown to be non-inferior to alteplase for the treatment of acute ischemic stroke within 4.5 hours of stroke onset. While not formally approved by regulatory authorities, many jurisdictions have transitioned to using tenecteplase for routine stroke treatment because it is simpler to use and has cost advantages.

We report a three-phase time-series analysis over 2.5 years and the process for transition from use of alteplase to tenecteplase for the routine treatment of acute ischemic stroke from a system-wide perspective involving an entire province. The transition was planned and implemented centrally. Data were collected in clinical routine, arising from both administrative sources and a prospective stroke registry, and represent real-world outcome data. Data are reported using standard descriptive statistics.

A total of 1211 patients were treated with intravenous thrombolysis (477 pre-transition using alteplase, 180 transition period using both drugs, 554 post-transition using tenecteplase). Baseline characteristics, adverse events and outcomes were similar between epochs. There were four dosing errors with tenecteplase, including providing the cardiac dose to two patients. There were no instances of major hemorrhage associated with dosing errors.

The transition to using intravenous tenecteplase for stroke treatment was seamless and resulted in identical outcomes to intravenous alteplase.

The best prehospital transport strategy for patients with suspected stroke due to possible large vessel occlusion varies by jurisdiction and available resources. A foundational problem is the lack of a definitive diagnosis at the scene. Rural stroke presentations provide the most problematic triage destination decision-making. In Alberta, Canada, the implementation and 5-year experience with a rural field consultation approach to provide service to rural patients with acute stroke is described.

The protocols established through the rural field consultation system and the subsequent transport patterns for suspected stroke patients during the first 5 years of implementation are presented. Outcomes are reported using home time and data are summarized using descriptive statistics.

From April 2017 to March 2022, 721 patients met the definition for a rural field consultation, and 601 patients were included in the analysis. Most patients (n = 541, 90%) were transported by ground ambulance. Intravenous thrombolysis was provided for 65 (10.8%) of patients, and 106 (17.6%) underwent endovascular thrombectomy. The median time from first medical contact to arterial access was 3.2 h (range 1.3–7.6) in the direct transfers, compared to 6.5 h (range 4.6–7.9) in patients arriving indirectly to the comprehensive stroke center (CSC). Only a small proportion of patients (n = 5, 0.8%) were routed suboptimally to a primary stroke center and then to a CSC where they underwent endovascular therapy.

The rural field consultation system was associated with shortened delays to recanalization and demonstrated that it is feasible to improve access to acute stroke care for rural patients.

We examined the return on investment (ROI) from the Endovascular Reperfusion Alberta (ERA) project, a provincially funded population-wide strategy to improve access to endovascular therapy (EVT), to inform policy regarding sustainability.

We calculated net benefit (NB) as benefit minus cost and ROI as benefit divided by cost. Patients treated with EVT and their controls were identified from the ESCAPE trial. Using the provincial administrative databases, their health services utilization (HSU), including inpatient, outpatient, physician, long-term care services, and prescription drugs, were compared. This benefit was then extrapolated to the number of patients receiving EVT increased in 2018 and 2019 by the ERA implementation. We used three time horizons, including short (90 days), medium (1 year), and long-term (5 years).

EVT was associated with a reduced gross HSU cost for all the three time horizons. Given the total costs of ERA were $2.04 million in 2018 ($11,860/patient) and $3.73 million in 2019 ($17,070/patient), NB per patient in 2018 (2019) was estimated at −$7,313 (−$12,524), $54,592 ($49,381), and $47,070 ($41,859) for short, medium, and long-term time horizons, respectively. Total NB for the province in 2018 (2019) were −$1.26 (−$2.74), $9.40 ($10.78), and $8.11 ($9.14) million; ROI ratios were 0.4 (0.3), 5.6 (3.9) and 5.0 (3.5). Probabilities of ERA being cost saving were 39% (31%), 97% (96%), and 94% (91%), for short, medium, and long-term time horizons, respectively.

The ERA program was cost saving in the medium and long-term time horizons. Results emphasized the importance of considering a broad range of HSU and long-term impact to capture the full ROI.

We have compared oxcarbazepine (OXC) with acamprosate (ACP) in relapse prevention in recently withdrawn alcohol dependent patients. Oxcarbazepine blocks voltage-sensitive sodium channels. Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, since acamprosate modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar affective disorders.

In a randomized open label pilot study 30 detoxified alcohol dependent patients were followed up for six months to assess treatment outcome in pharmacological relapse prevention. 15 alcoholics were treated with OXC and 15 with ACP. We asked for the time until first and heavy relapse and for drinks on drinking days. We assessed craving (OCDS), the severity of depression (ADS) and the degree of state anxiety (STAI).

After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients was not longer than for ACP patients. Abstinent patients in both study groups showed significantly lower OCDS-G than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol.

While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated. Thus, in medication-based relapse prevention, OXC could have the potential of a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or who suffer from affective lability. OXC certainly merits a larger placebo controlled trial.

In alcoholism, one relevant mechanism contributing to relapse is the exposure to stimuli that are associated with alcohol intake. Such conditioned cues can elicit conditioned responses like alcohol craving and consumption. In the last decade, considerable progress has been made in identifying basic neuronal mechanisms that underlie cue-induced alcohol craving.

We explored whether functional brain activation during exposure to alcohol-associated stimuli is related to the prospective relapse risk in detoxified alcohol-dependent patients.

46 alcohol-dependent and 46 healthy volunteers participated in a fMRI study using a cue reactivity paradigm, in which visual alcohol-related and control stimuli were presented. Patients were followed for 3 months. Afterwards data was analysed regarding the subsequent relapse, resulting in 16 abstainers and 30 relapsers.

Alcohol-related versus neutral stimuli activated a frontocortical-limbic network including inferior, medial and middle frontal gyrus as well as putamen in the group of patients relative to healthy controls. Moreover, abstainers showed a stronger activation in orbitofrontal cortex as well as midbrain during the presentation of alcohol-related cues whereas relapsers revealed a stronger activation of cingulate gyrus.

This study suggests that cue-induced activation of orbitofrontal cortex and dopaminergic innervated midbrain is negatively associated with the prospective relapse risk in alcohol-dependent patients. This could indicate a more pronounced and conscious processing of alcohol cues which might serve as a warning signal and a behavioural controlling function. In contrast, prospective relapsers showed a stronger activation of cingulate gyrus, a region involved in the attribution of motivational value.

We describe the efficacy and safety of as-needed use of nalmefene in the subgroup of patients with a high drinking risk level (DRL; men:>60g/day; women:>40g/day); i.e. a group of patients with a great unmet medical need for.

To evaluate the 6 month efficacy and safety of as-needed use of nalmefene 18mg versus placebo in a subgroup of alcohol-dependent patients with high DRL from a randomised controlled trial [NCT00812461].

All patients received a motivational and adherence-enhancing intervention (BRENDA) in combination with either nalmefene or placebo. Number of heavy drinking days (HDDs) and total alcohol consumption (TAC) were measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study.

The study population consisted of 317 patients: placebo N=162; nalmefene N=155 (mean age 44.8±10.3 years; 69% men; mean HDDs: 22±6.2/month; mean TAC 111±47.9g/day). Mean number of HDDs decreased to 10 days/month and mean TAC decreased to 43g/day at month 6 in the nalmefene group. There was a superior effect of nalmefene compared to placebo in reducing the number of HDDs (-2.7 [95% CI: -5.0;-0.3];p=0.0253) and TAC -10.3 [-20.2;-0.5];p=0.0404). Improvements in clinical status and alanine amino transferase were greater in the nalmefene group compared to the placebo group (p< 0.05). Adverse events were more common with nalmefene; incidence of adverse events leading to dropout was at the placebo level.

As-needed nalmefene was efficacious in reducing alcohol consumption in patients with high risk for alcoholrelated harm.

Switching from immediate release Methylphenidate (MPH-IR) to a sustained release formulation of MPH-IR in the treatment of ADHD is often required to provide better compliance and convenience; however switch was reported to be not always successful.

Small doses of MPH-IR may be added to sustained release preparations when its effect wears off.

Clinical case notes of 77 subjects aged 6–18 years who had been switched from MPH-IR to Concerta XL (an osmotic controlled-release formulation (OROS) of MPH) were retrospectively analysed for the effectiveness of the switch and the impact of an extra mid-afternoon dose of MPH-IR on the outcome.

Switch to Concerta XL alone was successful in 94% of cases and all 23 (100%) subjects who had MPH-IR added to Concerta XL showed good response to switch. More than 43% of patients required late afternoon top-up with MPH-IR to make a successful switch whilst 55% of patients required a larger dose of Concerta XL than the manufacturer's recommended equivalent to the existing dose of MPH-IR.

Higher than equivalent doses of Concerta XL or an additional dose of MPH-IR might be needed for a successful switch from short acting to sustained release MPH.

Although neuroimaging studies suggest brain regional abnormalities in depressive disorders, it remains unclear whether abnormalities are present at illness onset or reflect disease progression.

We hypothesized that cerebral variations were present in adolescents with subthreshold depression known to be at high risk for later full-blown depression.

We examined brain structural and diffusion-weighted magnetic resonance images of adolescents with subthreshold depression.

The participants were extracted from the European IMAGEN study cohort of healthy adolescents recruited at age 14. Subthreshold depression was defined as a distinct period of abnormally depressed or irritable mood, or loss of interest, plus two or more depressive symptoms but without diagnosis of Major Depressive Episode. Comparisons were performed between adolescents meeting these criteria and control adolescents within the T1-weighted imaging modality (118 and 475 adolescents respectively) using voxel-based morphometry and the diffusion tensor imaging modality (89 ad 422 adolescents respectively) using tract-based spatial statistics. Whole brain analyses were performed with a statistical threshold set to p< 0.05 corrected for multiple comparisons.

Compared with controls, adolescents with subthreshold depression had smaller gray matter volume in caudate nuclei, medial frontal and cingulate cortices; smaller white matter volume in anterior limb of internal capsules, left forceps minor and right cingulum; and lower fractional anisotropy and higher radial diffusivity in the genu of corpus callosum.

The findings suggest that adolescents with subthreshold depression have volumetric and microstructural gray and white matter changes in the emotion regulation frontal-striatal-limbic network.

We describe the efficacy and safety of as-needed use of nalmefene in the subgroup of patients with a high drinking risk level (DRL; men:>60g/day; women:>40g/day); i.e. a group of patients with a great unmet medical need for treatment.

To evaluate the 6 month efficacy and safety of as-needed use of nalmefene 18mg versus placebo in a subgroup of alcohol-dependent patients with high DRL from a randomised controlled trial [NCT00811720].

All patients received a motivational and adherence-enhancing intervention (BRENDA) in combination with either nalmefene or placebo. Number of heavy drinking days (HDDs) and total alcohol consumption (TAC) were measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study.

The study population consisted of 350 patients: placebo N=170; nalmefene N=180 (mean age 51.9±9.4 years; 63% men; mean HDDs: 23±5.7/month; mean TAC: 101±41.7g/day). Mean number of HDDs decreased to 11 days/month and mean TAC decreased to 44g/day at month 6 in the nalmefene group. There was a superior effect of nalmefene compared to placebo in reducing the number of HDDs (-3.7 [95% CI: -5.9;-1.5];p=0.0010) and TAC (-18.3 [-26.9;-9.7];p< 0.0001) at month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared to the placebo group (p< 0.05). Adverse events and adverse events leading to dropout were more common with nalmefene than placebo.

As-needed nalmefene was efficacious in reducing alcohol consumption in patients with high risk for alcoholrelated harm.