Long-acting injectable antipsychotics (LAIs) are among the most effective treatments in psychiatry, yet they remain underutilized in clinical practice. Although LAIs are typically used to maintain ...treatment adherence in patients with chronic schizophrenia, recent research has suggested that they may also provide an effective treatment strategy for patients with early-phase or first-episode disease. In October 2015, a group of 8 experts on the management of schizophrenia and LAIs met to evaluate the evidence surrounding the efficacy, safety, and cost-effectiveness of LAIs and to develop practical recommendations regarding the clinical use, education, and unmet needs related to LAIs. Participants were also asked to rate the importance of several patient characteristics when choosing an LAI versus an oral antipsychotic, from the perspectives of 4 different stakeholder groups: patients, health care professionals, families, and payers. The evidence review demonstrated that LAIs are superior to placebo for acute and maintenance treatment of schizophrenia and, in general, appear to be similar to one another in terms of schizophrenia relapse prevention. Study design impacts the demonstrated efficacy of LAIs versus oral antipsychotics, but recent database and randomized controlled studies favor the use of LAIs in early-phase schizophrenia patients. LAIs vary considerably in their propensity to cause certain adverse effects, including weight gain, metabolic effects, extrapyramidal symptoms, and prolactin elevation, and these differences can be used to help guide LAI selection. Some studies, but not all, have demonstrated significant reductions in health care utilization or overall costs with LAIs. The expert panel identified several barriers to LAI use in current practice, including clinician lack of knowledge, negative attitudes about LAIs, and resource and cost issues. The participants also identified a number of additional factors that should be considered when weighing the use of LAI therapy, including medication adherence, relapse risk and severity, cognitive impairment, ease of use, substance misuse, access and cost, stigma, social support, patient autonomy, control over medication dosing, fear of needles, and the potential for patient harm due to relapses and associated loss of functioning. This evidence review, discussion, and summary recommendations may help clinicians, patients, families, payers, and other stakeholders to better characterize the role of LAIs in the treatment of schizophrenia.
Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory ...potentials (SSEPs) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5–6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPs) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI.
The American Cancer Society's updated screening guidelines for prostate cancer (CaP) render digital rectal examination (DRE) optional. We investigated the impact of DRE on CaP detection among obese ...men. Data from 2794 men undergoing initial prostate biopsy at three centers were analyzed to assess CaP risk attributed to abnormal DRE across body mass index (BMI) categories. Predictive accuracies of a combination of PSA, age, race, center and biopsy year including or excluding DRE findings were compared by areas under the receiver-operating characteristics curves. In all cohorts, obese men were less likely to have abnormal DREs diagnosed than non-obese men. As BMI category increased, abnormal DREs became stronger predictors for overall CaP in individual (P-trends ≤ 0.05) and combined (P-trend<0.001) cohorts, and for high-grade CaP in the Italian (P-trend=0.03) and combined (P-trend=0.03) cohorts. DRE inclusion improved the predictive accuracy for overall and high-grade CaP detection among all obese men (P ≤ 0.032) but not normal-weight men (P ≥ 0.198). DRE inclusion also near-significantly improved overall CaP detection in obese men with PSA<4 ng ml(-1) (P=0.081). In conclusion, the predictive value of DRE is dependent on obesity and is significantly higher among obese men than normal-weight men.
Uridine diphosphate-glucuronosyltransferase 2B (UGT2B) enzymes conjugate testosterone metabolites to enable their excretion in humans. The functional significance of the UGT2B genetic variants has ...never been described in humans. We evaluated UGT2B variants in relation to plasma androstane-3α,17β-diol-glucuronide (AAG) levels and the prostate cancer risk.
AAG levels were measured in sera from 150 controls and compared to the polymorphisms of UGT2B17, UGT2B15, and UGT2B7. Genomic DNA from controls (301) and cases (148) was genotyped for the polymorphisms, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analyses. Having two copies of UGT2B17 was associated with higher AAG levels in controls among Whites (p=0.02), but not Blacks (p=0.82). Logistic regression models adjusting for age and race revealed that homozygosity for the G allele of the UGT2B15(D85Y) polymorphism was directly associated with the prostate cancer risk (OR=2.70, 95% CI=1.28, 5.55).
While the small sample size limits inference, our findings suggest that an association between the UGT2B17 copy number variant (CNV) and serum AAG levels in Whites, but unexpectedly not in Blacks. This novel observation suggests that genetic determinants of AAG levels in Blacks are unrelated to the UGT2B17 CNV. This study replicates the results that show an association of UGT215(D85Y) with an increased prostate cancer risk.
A hot leach method published by the World Health Organization for determining Pb and Cd in ceramic and enameled ware was collaboratively studied in 14 laboratories. The method consisted of heating a ...solution of 4% acetic acid at the boil for 2 h in 6 samples of specially glazed ceramic ware and 6 samples of special enameled ware. The acid was allowed to cool and stand in contact with the ware for an additional 22 h. At the end of the 2 h heating period and again at the end of the 24 h period, the leach solution was assayed by atomic absorption spectrophotometry for Pb and Cd. Ruggedness testing before the collaborative study revealed that: (1) the quantity of metal released increased as the average leach temperature approached the boiling point, (2) the quantity of Pb and Cd released from enameled ware increased linearly with time during 7 h of boiling, (3) the concentration of acid could be varied from 2 to 6% with no apparent effect on the amount of metal released, and (4) the room temperature (RT) contact period lasting from 22 to 120 h (after the 2 h heating period) did not increase the amount of metal released. The quantities of Pb and Cd measured by the collaborators at the end of 2 h of heating and after 24 h of total contact were essentially identical. The amounts of Pb and Cd were not related to the quantity of acid solution required to restore the leach solution volume to its initial value after boiling. The collaborative results showed that the period of standing at RT is not necessary and probably can be eliminated from the method. The modified method, which requires analysis of the leach solution immediately after the 2 h heating period, has been adopted interim official first action by AOAC.
PDF
