Adolescents and HIV: Prevention and clinical care

The incidence of HIV infection has increased to alarming proportions among minority youth, in particular among young men who have sex with men and among teenage girls. The unique socioeconomic, behavioral, and emotional vulnerability of adolescents for sexually transmitted diseases, including HIV, requires early identification of HIV infection for linkage to care. Differences in the clinical and psychosocial presentations of youth with perinatally versus behavioral acquired HIV infection are important and influence the acceptance of illness, self-efficacy, and antiretroviral treatment adherence. The ideal multidisciplinary team approach of culturally sensitive services for youth integrates clinical care, psychosocial and peer support interventions, transition planning, primary and secondary prevention, as well as comprehensive reproductive adolescent health services.     

Individual unmet needs for care: are they sensitive as outcome criterion for the effectiveness of mental health services interventions?

Background  Mental health interventions should demonstrate an effect on patients’ functioning as well as his/her needs, in particular on unmet needs whose assessment depends on the perspective of either the patient or the clinician. However, individual met and unmet needs appear to change over time, qualitatively and quantitatively, raising questions about their sensitivity to change and about the association between level of needs and treatment. Methods  Data on baseline and follow-up need assessment in community mental health services in four European countries in the context of a cluster randomised trial on a novel mental health service intervention were used, which involved 102 clinicians with key worker roles and 320 patients with schizophrenia or related psychotic disorders. Need assessment was performed with the Camberwell assessment of needs short appraisal schedule (CANSAS) among patients as well as clinicians. Focus is the sensitivity to change in unmet needs over time as well as the concordance between patient and clinician ratings and their relationship with treatment condition. Results  At follow-up 294 patients (92%) had a full need assessment, while clinician rated needs were available for 302 patients (94%). Generally, the total number of met needs remained quite stable, but unmet needs decreased significantly over time, according to patients as well as to clinicians. Sensitivity to change of unmet needs is quite high: about two third of all unmet needs made a transition to no or met need, and more than half of all unmet needs at follow-up were new. Agreement between patient and clinician on unmet needs at baseline as well as follow-up was rather low, without any indication of a specific treatment effect. Conclusions  Individual unmet needs appear to be quite sensitive to change over time but as yet less suitable as outcome criterion of treatment or specific interventions.     

Basolateral amygdala involvement in memory reconsolidation processes that facilitate drug context-induced cocaine seeking

Understanding the neurobiological underpinnings of putative memory stabilization processes that maintain context–response–cocaine associations in long‐term memory and underlie contextual control over addictive behavior is of great interest from an addiction treatment perspective. Using an instrumental animal model of contextual drug relapse we show that the protein synthesis inhibitor anisomycin, administered into the basolateral amygdala (BLA) immediately after limited (15‐ or 60‐min) re‐exposure to a previously cocaine‐paired context, subsequently disrupted the ability of the previously cocaine‐paired context to reinstate extinguished cocaine‐seeking behavior relative to vehicle. Consistent with a BLA‐mediated memory reconsolidation deficit, a similar impairment in cocaine‐seeking behavior was not observed in (i) ‘no‐reactivation’ control groups that received anisomycin into the BLA after (re)exposure to either a novel unpaired or an extinction‐paired context or in (ii) a neuroanatomical control group that received anisomycin into the posterior caudate–putamen, dorsally adjacent to the BLA, after re‐exposure to the cocaine‐paired context. Furthermore, anisomycin administered into the BLA after brief (5‐min) or extensive (120‐min) re‐exposure to the cocaine‐paired context (which was sufficient to extinguish cocaine‐seeking behavior in a vehicle control group) also failed to alter responding. Together, these findings suggest that re‐exposure to a cocaine‐paired context in the absence of cocaine reinforcement is sufficient to trigger memory reconsolidation processes that support future drug‐seeking behavior. The presence and duration of drug‐related memory reactivation critically influences, and anisomycin‐sensitive mechanisms in the BLA selectively control, this phenomenon. These findings support the feasibility of novel pharmacotherapeutic approaches that selectively inhibit the reconsolidation of cocaine‐related memories in order to prevent drug relapse.     

Sleep disordered breathing in patients with acutely decompensated heart failure

Objective: The purpose of this study is to systematically characterize sleep disordered breathing (SDB) during acute heart failure (HF) decompensation.Background: SDB, both Cheyne–Stokes breathing (CSB) and obstructive sleep apnea, is common in stable congestive HF patients, but its presence and characteristics in decompensated HF is unknown.Methods: Eighteen men and 11 women (mean age 57 ± 17 years, plasma brain-natriuretic peptide 1660 ± 1179 pg/ml, left ventricular ejection fraction 20 ± 6%) admitted with decompensated systolic HF without other active cardiorespiratory morbidity underwent echocardiography and overnight bedside polysomnography within 48 h of admission. Ten patients underwent follow-up polysomnography just before or immediately after hospital discharge.Results: Twenty-eight of 29 patients demonstrated an apnea + hypopnea index (AHI) > 5 events/h (mean AHI 41 ± 29/h); 22 patients had an AHI > 15/h. SDB was predominantly CSB (central events 39 ± 29/h; obstructive events 2 ± 2/h, p < 0.001). Time in CSB was 51 ± 33% of total sleep time (TST); nadir oxygen saturation (SaO₂) was 81 ± 10%. SDB was similar on admission vs. follow-up polysomnography (mean AHI 44 ± 39/h vs. 38 ± 31/h; CSB 53 ± 38% vs. 46 ± 37% TST). Follow-up polysomnography showed a higher nadir SaO₂ than admission (84 ± 11% vs. 79 ± 12%, p = 0.05), but TST with SaO₂ < 90% was not reduced.Conclusions: CSB is common and severe in patients hospitalized with decompensated HF. Acute treatment of HF does not consistently improve CSB. The effect of CSB on ventricular function and prognosis in decompensated HF remains to be demonstrated.     

Mitochondria-targeted nitroxides exacerbate fluvastatin-mediated cytostatic and cytotoxic effects in breast cancer cells

Mito-CP11, a mitochondria-targeted nitroxide formed by conjugating a triphenylphosphonium cation to a five-membered nitroxide, carboxy-proxyl (CP), has been used as a superoxide dismutase (SOD) mimetic. In this study, we investigated the antiproliferative and cytotoxic properties of submicromolar levels of Mito-CP11 alone and in combination with fluvastatin, a well known cholesterol lowering drug, in breast cancer cells. Mito-CP11, but not CP or CP plus the cationic ligand, methyl triphenylphosphonium (Me-TPP+), inhibited MCF-7 breast cancer cell proliferation. Mito-CP11 had only minimal effect on MCF-10A, non-tumorigenic mammary epithelial cells. Mito-CP11, however, significantly enhanced fluvastatin-mediated cytotoxicity in MCF-7 cells. Mito-CP11 alone and in combination with fluvastatin inhibited nuclear factor kappa-B activity mainly in MCF-7 cells. We conclude that mitochondria-targeted nitroxide antioxidant molecules (such as Mito-CP11) that are non-toxic to non-tumorigenic cells could enhance the cytostatic and cytotoxic effects of statins in breast cancer cells. This strategy of combining mitochondria-targeted non-toxic molecules with cytotoxic chemotherapeutic drugs may be successfully used to enhance the efficacy of antitumor therapies in breast cancer treatment.     

Fluoride varnish: the top choice for professionally applied fluoride

Although various modes of delivery for professionally applied fluoride exist, one form has emerged that combines caries prevention efficacy with safety and versatility. The American Dental Association Council on Scientific Affairs recommends fluoride varnish as the only professionally applied fluoride for moderate to high risk patients of all age groups. In addition to demonstrating effectiveness equivalent to fluoride gels, fluoride varnish provides improved safety and acceptability. Furthermore, fluoride varnish has shown promise in preventing dental caries in special groups, such as orthodontic patients and the elderly.     

Notification of Abnormal Lab Test Results in an Electronic Medical Record: Do Any Safety Concerns Remain?

Background

Follow-up of abnormal outpatient laboratory test results is a major patient safety concern. Electronic medical records can potentially address this concern through automated notification. We examined whether automated notifications of abnormal laboratory results (alerts) in an integrated electronic medical record resulted in timely follow-up actions.

Methods

We studied 4 alerts: hemoglobin A1c ≥15%, positive hepatitis C antibody, prostate-specific antigen ≥15 ng/mL, and thyroid-stimulating hormone ≥15 mIU/L. An alert tracking system determined whether the alert was acknowledged (ie, provider clicked on and opened the message) within 2 weeks of transmission; acknowledged alerts were considered read. Within 30 days of result transmission, record review and provider contact determined follow-up actions (eg, patient contact, treatment). Multivariable logistic regression models analyzed predictors for lack of timely follow-up.

Results

Between May and December 2008, 78,158 tests (hemoglobin A1c, hepatitis C antibody, thyroid-stimulating hormone, and prostate-specific antigen) were performed, of which 1163 (1.48%) were transmitted as alerts; 10.2% of these (119/1163) were unacknowledged. Timely follow-up was lacking in 79 (6.8%), and was statistically not different for acknowledged and unacknowledged alerts (6.4% vs 10.1%; P =.13). Of 1163 alerts, 202 (17.4%) arose from unnecessarily ordered (redundant) tests. Alerts for a new versus known diagnosis were more likely to lack timely follow-up (odds ratio 7.35; 95% confidence interval, 4.16-12.97), whereas alerts related to redundant tests were less likely to lack timely follow-up (odds ratio 0.24; 95% confidence interval, 0.07-0.84).

Conclusions

Safety concerns related to timely patient follow-up remain despite automated notification of non-life-threatening abnormal laboratory results in the outpatient setting.