Tuberculosis vaccine development is hindered by the lack of validated immune correlates of protection. Exploring immune correlates of risk of disease and/or infection in prospective samples can ...inform this field. We investigate whether previously identified immune correlates of risk of TB disease also associate with increased risk of M.tb infection in BCG-vaccinated South African infants, who became infected with M.tb during 2-3 years of follow-up. M.tb infection is defined by conversion to positive reactivity in the QuantiFERON test. We demonstrate that inflammation and immune activation are associated with risk of M.tb infection. Ag85A-specific IgG is elevated in infants that were subsequently infected with M.tb, and this is coupled with upregulated gene expression of immunoglobulin-associated genes and type-I interferon. Plasma levels of IFN-Formula: see text2, TNF-Formula: see text, CXCL10 (IP-10) and complement C2 are also higher in infants that were subsequently infected with M.tb.
We assessed the impact of medical comorbidities, depression, and treatment intensity on quality of life in a large primary care cohort of patients with type 2 diabetes.
We used the Health Utilities ...Index-III, an instrument that measures health-related quality of life based on community preferences in units of health utility (scaled from 0=death to 1.0=perfect health), in 909 primary care patients with type 2 diabetes. Demographic and clinical correlates of health-related quality of life were assessed.
The median health utility score for this population was 0.70 (interquartile range 0.39-0.88). In univariate analyses, older age, female sex, low socioeconomic status, cardiovascular disease, microvascular complications, congestive heart failure, peripheral vascular disease, chronic lung disease, depression, insulin use and number of medications correlated with decreased quality of life, while obesity, hypertension and hypercholesterolaemia did not. In multiple regression analyses, microvascular complications, heart failure and depression were most strongly related to decreased health-related quality of life, independently of duration of diabetes; in these models, diabetes patients with depression had a utility of 0.59, while patients without symptomatic comorbidities did not have a significantly reduced quality of life. Treatment intensity remained a significant negative correlate of quality of life in multivariable models.
Patients with type 2 diabetes have a substantially decreased quality of life in association with symptomatic complications. The data suggest that treatment of depression and prevention of complications have the greatest potential to improve health-related quality of life in type 2 diabetes.
Aims
To evaluate the effectiveness of automated symptom and side effect monitoring on quality of life among individuals with symptomatic diabetic peripheral neuropathy.
Methods
We conducted a ...pragmatic, cluster randomized controlled trial (July 2014 to July 2016) within a large healthcare system. We randomized 1834 primary care physicians and prospectively recruited from their lists 1270 individuals with neuropathy who were newly prescribed medications for their symptoms. Intervention participants received automated telephone‐based symptom and side effect monitoring with physician feedback over 6 months. The control group received usual care plus three non‐interactive diabetes educational calls. Our primary outcomes were quality of life (EQ‐5D) and select symptoms (e.g. pain) measured 4–8 weeks after starting medication and again 8 months after baseline. Process outcomes included receiving a clinically effective dose and communication between individuals with neuropathy and their primary care provider over 12 months. Interviewers collecting outcome data were blinded to intervention assignment.
Results
Some 1252 participants completed the baseline measures mean age (sd): 67 (11.7), 53% female, 57% white, 8% Asian, 13% black, 20% Hispanic. In total, 1179 participants (93%) completed follow‐up (619 control, 560 intervention). Quality of life scores (intervention: 0.658 ± 0.094; control: 0.653 ± 0.092) and symptom severity were similar at baseline. The intervention had no effect on primary EQ‐5D: −0.002 (95% CI −0.01, 0.01), P = 0.623; pain: 0.295 (−0.75, 1.34), P = 0.579; sleep disruption: 0.342 (−0.18, 0.86), P = 0.196; lower extremity functioning: −0.079 (−1.27, 1.11), P = 0.896; depression: −0.462 (−1.24, 0.32); P = 0.247 or process outcomes.
Conclusions
Automated telephone monitoring and feedback alone were not effective at improving quality of life or symptoms for people with symptomatic diabetic peripheral neuropathy.
Trial Registration: ClinicalTrials.gov (NCT02056431).
What's new?
Frequent communication between individuals with diabetic peripheral neuropathy and primary care providers about symptoms and medication side effects is critical to optimizing medication dosing to treat painful diabetic peripheral neuropathy. Yet, there are considerable barriers to effective communication.
This cluster randomized controlled trial found that a brief intervention to automatically monitor person‐reported data on symptoms and side effects, and provide the information to physicians via an electronic health record was not effective in improving the outcomes valued by individuals with neuropathy.
Alerts alone are unlikely to change provider behaviour related to treatment intensification. More intensive interventions focused on individual activation or provider education may be more effective in changing prescribing behaviour and improving outcomes.
Nicotine is a highly addictive drug found in tobacco that drives its continued use despite the harmful consequences. The initiation of nicotine abuse involves the mesolimbic dopamine system, which ...contributes to the rewarding sensory stimuli and associative learning processes in the beginning stages of addiction. Nicotine binds to neuronal nicotinic acetylcholine receptors (nAChRs), which come in a diverse collection of subtypes. The nAChRs that contain the α4 and β2 subunits, often in combination with the α6 subunit, are particularly important for nicotine's ability to increase midbrain dopamine neuron firing rates and phasic burst firing. Chronic nicotine exposure results in numerous neuroadaptations, including the upregulation of particular nAChR subtypes associated with long-term desensitization of the receptors. When nicotine is no longer present, for example during attempts to quit smoking, a withdrawal syndrome develops. The expression of physical withdrawal symptoms depends mainly on the α2, α3, α5, and β4 nicotinic subunits in the epithalamic habenular complex and its target regions. Thus, nicotine affects diverse neural systems and an array of nAChR subtypes to mediate the overall addiction process.
This article is part of the special issue on ‘Contemporary Advances in Nicotine Neuropharmacology’.
•Nicotine is highly addictive and is a leading cause of premature death worldwide.•Great diversity in neuronal nicotinic acetylcholine receptors arises from their subunit composition.•Genetic factors, especially within the CHRNA5-A3-B4 gene cluster, play an important role in nicotine addiction.•Midbrain dopamine systems play an important role especially in the initiation of nicotine use.•Aspects of nicotine withdrawal are mediated by the habenulo-interpeduncular pathway.
Aims To characterize the determinants of diabetes‐related emotional distress by treatment modality (diet only, oral medication only, or insulin).
Methods A total of 815 primary care patients with ...Type 2 diabetes completed the Problem Areas in Diabetes (PAID) Scale and other questions. We linked survey data to a diabetes clinical research database and used linear regression models to assess the associations of treatment with PAID score.
Results PAID scores were significantly higher among insulin‐treated (24.6) compared with oral‐treated (17.8, P < 0.001) or diet‐treated patients (14.7, P < 0.001), but not different between oral‐ vs. diet‐treated patients (P = 0.2). Group scores remained similar, but the statistical significance of their differences was reduced and ultimately eliminated after sequential adjustment for diabetes severity, HbA1c, body mass index, regimen adherence, and self‐blood‐glucose monitoring. Insulin‐treated patients reported significantly higher distress than oral‐ or diet‐treated patients on 16 of 20 PAID items. ‘Worrying about the future’ and ‘guilt/anxiety when … off track with diabetes’ were the top two serious problems (PAID ≥ 5) in all treatment groups. Not accepting diabetes diagnosis was a top concern for oral‐ and diet‐treated patients, and unclear management goals distressed diet‐treated patients.
Conclusions Primary care patients treated with insulin reported higher diabetes‐related emotional distress compared with oral‐ or diet‐treated patients. Greater distress was largely explained by greater disease severity and self‐care burdens. To improve diabetes‐specific quality of life, clinicians should address patients’ sense of worry and guilt, uncertain acceptance of diabetes diagnosis, and unclear treatment goals.
Highlights • We examine short-term health utility of patients on opioid agonist treatment (OAT). • OAT initially improves health utility across all treatment modalities and patients. • Health utility ...subsequently decreases slightly or increases at diminished rate. • Results suggest a threshold level in health-related quality of life response to OAT.
The immunogenicity of the candidate tuberculosis (TB) vaccine MVA85A may be enhanced by aerosol delivery. Intradermal administration was shown to be safe in adults with latent TB infection (LTBI), ...but data are lacking for aerosol-delivered candidate TB vaccines in this population. We carried out a Phase I trial to evaluate the safety and immunogenicity of MVA85A delivered by aerosol in UK adults with LTBI (NCT02532036). Two volunteers were recruited, and the vaccine was well-tolerated with no safety concerns. Aerosolised vaccination with MVA85A induced mycobacterium- and vector-specific IFN-γ in blood and mycobacterium-specific Th1 cytokines in bronchoalveolar lavage. We identified several important barriers that could hamper recruitment into clinical trials in this patient population. The trial did not show any safety concerns in the aerosol delivery of a candidate viral-vectored TB vaccine to two UK adults with
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infection. It also systemically and mucosally demonstrated inducible immune responses following aerosol vaccination. A further trial in a country with higher incidence of LTBI would confirm these findings.
To describe the risk factors, clinical course, and complications of migration of a dexamethasone (DEX) intravitreal implant (OZURDEX; Allergan, Inc., Irvine, CA) into the anterior chamber and ...subsequent management strategies.
Retrospective, observational case series.
Fifteen patients had 18 episodes of migration of the DEX implant into the anterior chamber.
The medical records of 15 patients with spontaneous migration of a DEX implant were retrospectively reviewed.
Migration of the DEX implant into the anterior chamber.
Migration of a DEX intravitreal implant into the anterior chamber occurred in 6 patients who were aphakic, 4 patients with an anterior chamber intraocular lens, 2 patients with a scleral-fixated posterior chamber intraocular lens (PCIOL), 2 patients with a PCIOL, and 1 patient with an iris-fixated PCIOL. All 15 patients had prior pars plana vitrectomy, and 14 patients (93%) had no lens capsule. The average interval from DEX implant injection to detection of the implant migration into the anterior chamber was 13 days (range, 5-44 days). In 14 patients, corneal edema developed. Among those eyes undergoing surgical removal of the implant, earlier intervention reduced the likelihood of permanent corneal edema (0.5 days from diagnosis of migration to surgical removal of the implant vs. 5.5 days; P = 0.04). Aspiration was necessary to remove the implant in 6 patients. Among the 14 patients with corneal edema, the corneal edema did not resolve in 10 patients (71%), 6 (43%) of whom required corneal transplantation.
Absence of lens capsule and prior vitrectomy are risk factors for migration of the DEX implant into the anterior chamber. Early removal of the implant may be necessary to minimize the risk of chronic corneal edema.
PARKER OLIVER P., DEMIRIS G., WITTENBERG‐LYLES E. & POROCK D. (2010) European Journal of Cancer Care19, 729–735 The use of videophones for patient and family participation in hospice ...interdisciplinary team meetings: a promising approach
Inclusion of patients and caregivers in decisions related to the delivery of care is inherent in the hospice philosophy. Telemedicine technologies offer a potential solution to the challenges presented by the geographic distance between team meetings and the home environment. While inclusion requires additional coordination by the hospice team, it also offers an important opportunity to improve communication between the team and the patient and family. A modified conceptual model based on two previous frameworks is outlined to support patient and family involvement in hospice team meetings. Further research is suggested to determine the structural feasibility of patient and family involvement via videophone as well as the structural and procedural changes resulting from this inclusion. Finally, clinical outcomes and family evaluation of the inclusion experience need to be thoroughly researched before final conclusions may be reached.
Disruption of neuronal chloride ion (Cl−) homeostasis has been linked to several pathological conditions, including substance use disorder, yet targeted pharmacotherapies are lacking. In this study, ...we explored the potential of serotonin 2A receptor (5‐HT2AR) agonism to reduce alcohol consumption in male wild‐type C57Bl/6J mice and to ameliorate alcohol‐induced inhibitory plasticity in the midbrain. We found that administration of the putative 5‐HT2AR agonist TCB‐2 attenuated alcohol consumption and preference but did not alter water or saccharin consumption. We hypothesized that the selective behavioural effects of TCB‐2 on alcohol drinking were due, at least in part, to effects of the agonist on ventral tegmental area (VTA) neurocircuitry. Alcohol consumption impairs Cl− transport in VTA GABA neurons, which acts as a molecular adaptation leading to increased alcohol self‐administration. Using ex vivo electrophysiological recordings, we found that exposure to either intermittent volitional alcohol drinking or an acute alcohol injection diminished homeostatic Cl− transport in VTA GABA neurons. Critically, in vivo TCB‐2 administration normalized Cl− transport in the VTA after alcohol exposure. Thus, we show a potent effect of alcohol consumption on VTA inhibitory circuitry, in the form of dysregulated Cl− homeostasis that is reversible with agonism of 5‐HT2ARs. Our results provide insight into the potential therapeutic action of 5‐HT2AR agonists for alcohol abuse.
Using volitional or experimenter‐administered alcohol (ethanol, EtOH) exposure in mice, we determined the consequences of the psychedelic‐like compound TCB‐2 on EtOH‐induced midbrain plasticity and behaviour. Electrophysiological recordings of ventral tegmental area (VTA) GABA neurons revealed chloride ion dysregulation following EtOH exposure that could be reversed with TCB‐2 intervention. In parallel, TCB‐2 reduced ongoing EtOH consumption suggesting that restoration of VTA chloride homeostasis may contribute to beneficial effects seen with other psychedelic drugs when given to humans with alcohol use disorder.
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