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Background We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). Methods The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. Results Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/μL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. Conclusion While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that the incidence of idiopathic pulmonary fibrosis (IPF) is rising in the U.K. and U.S.A. Death registrations and primary care data were used to determine the current trends in IPF incidence in the U.K. Because routine clinical data sets were used, the term IPF clinical syndrome (IPF-CS) is used to describe individuals in this study.Methods: Age- and stratum-specific death registration rates between 1968 and 2008 were calculated and these were applied to the 2008 population to generate annual standardised expected number of deaths. Annual mortality rate ratios were calculated using Poisson regression. Computerised primary care records were used to determine incidence rates of IPF-CS between 2000 and 2008 stratified by age, sex and geographical region, and survival rates between calendar periods were compared.Results: Annual death certificate recording of IPF-CS rose sixfold across the study period from 0.92 per 100,000 in the 1968-1972 calendar periods to 5.10 per 100,000 in the 2006-2008 calendar period, and were higher in men and the older age groups. The incidence of IPF-CS in primary care increased by 35% from 2000 to 2008, with an overall incidence rate of 7.44 per 100,000 person-years (95% CI 7.12 to 7.77). Incidence was higher in men, the older population and in Northwest England.Conclusions: The incidence of IPF-CS in primary care and registered deaths from this cause in the U.K. continues to rise in the 21st century. The current findings suggest that there are >5000 new cases diagnosed each year in the U.K. [ABSTRACT FROM AUTHOR]

Review a number of cases in which the incorporation of HFA has allowed for a better understanding of diagnostics and patient management options. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This article reviews and compares the tolerability profiles of atypical antipsychotics in adults with schizophrenia or bipolar disorder in randomized controlled trials (RCTs). METHODS: A systematic search of the BIOSIS, Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and PsycINFO databases was conducted for English-language papers and abstracts that reported RCTs comparing > or =2 atypical antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) in the treatment of adult patients with schizophrenia or bipolar disorder. The search was completed in December 2007. A panel of 4 psychiatrists with expertise in the treatment of schizophrenia, schizoaffective disorder, or bipolar disorder identified potentially relevant outcomes that would reflect patients' subjective perception of adverse effects during treatment with antipsychotic medications. These outcomes were daily activities, anxiety or depression, bodily anxiety or restlessness, dizziness or nausea, extrapyramidal symptoms (EPS), sexual dysfunction, stiffness or tremor, tiredness or weakness, and weight gain. Data on these outcomes were extracted from relevant studies, and mixed treatment comparisons were conducted using Bayesian Markov Chain Monte Carlo simulation. Summary effect estimates (odds ratios [ORs] and 95% credible intervals [95% CrIs]) were calculated and reported in comparison with risperidone. RESULTS: The search identified 2963 potentially relevant publications, of which 50 provided data on 48 RCTs comparing > or =2 atypical antipsychotics. Outcomes that were statistically significant compared with risperi-done at the 5% level were decreased bodily anxiety or restlessness with quetiapine (OR = 0.506; 95% CrI = 0.290, 0.789), decreased EPS with quetiapine (OR = 0.441; 95% CrI = 0.129, 0.910), increased weight gain with olanzapine (OR = 2.139; 95% CrI = 1.764, 2.626), and decreased weight gain with ziprasidone (OR = 0.466; 95% CrI = 0.317, 0.657). CONCLUSION: The atypical antipsychotics had mixed tolerability profiles in this mixed treatment comparison, with some agents having significantly greater tolerability than others depending on the outcome assessed. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to describe the relationship between age and the time to treatment discontinuation in the absence of virological failure as well as the development of specific laboratory abnormalities, in patients starting highly active antiretroviral therapy (HAART) for the first time. Methods Analyses included 8708 antiretroviral-naïve patients from the UK Collaborative HIV Cohort (CHIC) study who started HAART from 1998 onwards. We considered time to the first discontinuation of any drug in the initial HAART regimen for reasons other than virological failure; the association between this and age at the start of HAART was determined using proportional hazards regression after adjustment for potential confounders. The incidence of specific laboratory abnormalities in the first year after starting HAART was compared in those of different ages using multiple logistic regression. Results A total of 2650 patients discontinued at least one drug in their HAART regimen in the first year for reasons other than virological failure; after controlling for confounders, those aged < 30 years at the time of starting HAART were more likely to discontinue than those aged 30–39 years [relative hazard (RH) 1.12; 95% confidence interval (CI) 1.01, 1.24] as were those aged ⩾ 50 years (RH 1.14; 95% CI 1.00, 1.31). There were strong associations between greater age and raised total cholesterol, decreased haemoglobin and raised triglycerides over the first year, although the latter disappeared after adjustment for pre-HAART levels, suggesting that this finding reflected higher pre-HAART triglyceride levels in older individuals. Conclusions Continued attempts to improve the tolerability of HAART regimens may help to sustain the good outcomes in all age groups over the longer term. [ABSTRACT FROM AUTHOR]

We describe the combined use of inhaled nitric oxide and heliox (79% helium and 21% oxygen) as a rescue therapy for a critically ill infant with localized interstitial pulmonary emphysema and pulmonary hypertension. Conventional interventions were ineffective, not feasible, or unlikely to take effect in time, during this infant's acute critical illness. We added heliox based on its known pulmonary effects, and inhaled nitric oxide to improve oxygenation, after echocardiographic evidence of high right-ventricular pressure. The infant made a full recovery. To our knowledge this is the first case report of heliox and inhaled nitric oxide used simultaneously in localized interstitial pulmonary emphysema. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the study were to describe gender differences in haemoglobin and albumin and to investigate the prognostic value of these measurements in relation to highly active antiretroviral therapy (HAART). Methods: Anaemia was defined as haemoglobin <13.5 g/dL for men and <11.5 g/dL for women. Albumin <35 g/L was defined as hypoalbuminaemia. Proportional hazards models were used to describe relationships between these markers and HIV progression and death. Results: A total of 291 patients had pre-HAART and 1-year measurements. Mean haemoglobin and albumin levels pre-HAART were lower in women than in men (haemoglobin: 11.2 vs 13.2 g/dL, respectively, P<0.0001; albumin: 37.4 vs 40.2 g/L, respectively, P<0.0001), and a higher proportion of women were anaemic and hypoalbuminaemic compared with men. Despite a rise in both markers in the first year on HAART, mean haemoglobin levels remained lower by 2.08 g/dL ( P<0.0001) and albumin by 2.88 g/L ( P<0.0001) in women. In the 495 patients included in this analysis, haemoglobin and albumin levels were both significantly related to short-term risk of AIDS and death independently of CD4 count [hazards ratio (HR)=0.73/g/dL higher haemoglobin, 95% confidence interval (CI) 0.55-0.82, P<0.0001 and HR=0.87/g/L higher albumin, 95% CI 0.83-0.91, P<0.0001]. The prognostic value did not differ by gender. Conclusions: Women were more likely to be anaemic and/or hypoalbuminaemic pre-HAART, but post-HAART increases were similar to those in men. Both haemoglobin and albumin were strong independent prognostic factors for risk of AIDS and death, regardless of gender. [ABSTRACT FROM AUTHOR]

Background: Relatively few data are available on the association between the use of specific antiretroviral drugs and the rate of viral rebound in those attaining a viral load (VL) <50 copies/mL while receiving highly active antiretroviral therapy (HAART).Methods: Patients achieving a VL <50 copies/mL for the first time while receiving HAART were followed until viral rebound (2 consecutive VLs >500 copies/mL). Pre-HAART antiretroviral-naive patients were analyzed separately from those with nucleoside reverse transcriptase inhibitor (NRTI) experience.Results: Of 3565 suppressed antiretroviral-naive patients, 381 experienced viral rebound (rate, 6.26 events/100 person-years of follow-up [pyrs] [95% confidence interval {CI}, 5.63-6.89 events/100 pyrs]). For those receiving efavirenz, the rate was 4.08 (95% CI, 3.16-5.01) events/pyrs. Compared with this, the rebound rate for those receiving indinavir was 1.52 times higher (rate ratio [RR], 1.52 [95% CI, 0.82-2.84]). RRs (95% CIs) for other drugs were: soft-gel saquinavir, 0.54 (0.07-3.97); nelfinavir, 2.44 (1.68-3.54); indinavir/ritonavir, 1.96 (1.02-3.77); saquinavir/ritonavir, 1.12 (0.48-2.61); lopinavir/ritonavir, 1.23 (0.58-2.59); nevirapine, 1.53 (1.11-2.10); and abacavir, 2.03 (1.26-3.25). Of 810 NRTI-exposed patients, 145 experienced viral rebound (rate, 8.29 [95% CI, 6.94-9.64] events/pyrs). For those receiving efavirenz, the rate was 5.25 (95% CI, 3.11-8.30) events/pyrs. Compared with this, the RRs (95% CIs) were: indinavir, 1.75 (0.82-3.73); hard-gel saquinavir, 3.48 (0.36-33.37); nelfinavir, 2.64 (1.37-5.08); indinavir/ritonavir, 0.32 (0.04-2.49); saquinavir/ritonavir, 0.64 (0.23-1.80); nevirapine, 1.65 (0.90-3.02); and abacavir, 1.82 (0.73-4.52).Conclusions: We must make comparisons of antiretroviral outcomes in observational data with caution; however, our results suggest that, in those with VLs <50 copies/mL, certain drugs may be associated with higher rebound rates than others. [ABSTRACT FROM AUTHOR]

The purpose of this qualitative study was to explore spiritual care for dying nursing home residents from the perspectives of registered nurses, practical nurses, certified nursing assistants, advanced practice nurses, and physicians. Five major themes emerged: honoring the person's dignity, intimate knowing in the nursing home environment, wishing we could do more, personal knowing of self as caregiver, and struggling with end-of-life treatment decisions. Spiritual caring was described within the context of deep personal relationships, holistic care, and support for residents. Spiritual care responses and similarities and differences in the experiences of participants are presented. Education and research about how to assist residents and families as they struggle with difficult end-of-life decisions, adequate time and staff to provide the kind of care they 'wished they could,' and development of models that honor the close connection and attachment of staff to residents could enhance end-of-life care in this setting. [ABSTRACT FROM AUTHOR]

Objective: Autism/autistic disorder (MIM number 209850) is a complex, largely genetic psychiatric disorder. The authors recently mapped a susceptibility locus for autism to chromosome region 2q24-q33 (MIM number 606053). In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region.Method: Mutation screening of positional candidate genes was performed in two stages. The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). In the second stage, the two SNPs in SLC25A12 were further genotyped in 411 autistic families, and linkage and association tests were carried out in the 197 informative families.Results: Linkage and association were observed between autistic disorder and the two SNPs, rs2056202 and rs2292813, found in SLC25A12. Using either a single affected subject per family or all affected subjects, evidence for excess transmission was found by the Transmission Disequilibrium Test for rs2056202, rs2292813, and a two-locus G*G haplotype. Similar results were observed using TRANSMIT for the analyses. Evidence for linkage was supported by linkage analysis with the two SNPs, with a maximal multipoint nonparametric linkage score of 1.57 and a maximal multipoint heterogeneity lod score of 2.11. Genotype relative risk could be estimated to be between 2.4 and 4.8 for persons homozygous at these loci.Conclusions: A strong association of autism with SNPs within the SLC25A12 gene was demonstrated. Further studies are needed to confirm this association and to decipher any potential etiological role of AGC1 in autism. [ABSTRACT FROM AUTHOR]

Grandparents caring for their grandchildren is among the oldest practices in child rearing with roots embedded in the traditions across many cultures. However, in recent years, the issue of 'grandparents raising their grandchildren' has garnered the attention of researchers, advocates, service providers and even the popular press. Dynamic changes in family life, related social trends and child welfare policies in the United States have resulted in dramatic growth of intergenerational caregiving among this population. The 2000 United States Census shows that there are 6 million children living in grandparentand other relativemaintained households, which represents a thirty-percent increase from the last Census. This growth has created the need for effective federal policies that support and insure the well-being of these families. This paper examines some of the reasons grandparents raising grandchildren are capturing public attention, and the growing needs for effective federal policies that support this burgeoning population. We will (1) provide a brief demographic sketch of grandparent-headed families, (2) identify some of the challenges faced by these families, and (3) explore some of the most effective federal public policies, in particular the new National Family Caregiver Support Program, which are emerging from an intergenerational agenda directed at assisting these families. We conclude by noting that the issue of 'grandparents raising their grandchildren' presents a unique opportunity to develop coalitions and policies that cross sometimes rigidly defined age-based policy structures. [ABSTRACT FROM AUTHOR]

In recent years the issue of 'grandparents raising their grandchildren' seems to have leapt into the consciousness of researchers, advocates, service providers, policy analysts and the general public. Current estimates indicate that there are 2.5 million American households headed by grandparents (U. S. Bureau of the Census, 1998). This article explores the development of this issue, seeking to (1) explain why it is capturing the attention of some advocates, researchers and policymakers, (2) identify the challenges for grandparent-headed families and (3) explore public policies and programs emerging from a developing intergenerational agenda directed at assisting such families. [ABSTRACT FROM AUTHOR]

Many factors affect the home health care agency of today, creating a challenge for leaders. Internal and external factors are presenting rapid change, unprecedented in our history. Health care costs, technology, changes in health care financing and regulations, patient uncertainty in dealing with changes, and safety issues are only some of the challenges that can consume time and energies of a home care leader. These challenges present opportunities that could not only work positively for the agency but could often cause leaders to forget the basic ethical values related to treating employees in a way that positively influences development, gives employees a sense of worth, and compassionately supports them through change. If the leader intentionally considers these values, the leadership role will be effective by not only having a positive impact upon the employee but by positively influencing the success of the agency. One key to accomplishing this is the home care leader's understanding of the motivations behind human behavior. In an agency where employees are valued, the opportunities for success are manageable and the key to success is basic. Ethical leadership intentionally focuses upon the basic values and motivates employees to maximize their potential. When leadership is not approached in this manner, it is ethically compromised. The challenge for ethical success is not to forget these basic values. [ABSTRACT FROM AUTHOR]

A 79-year-old lady presented with subclinical autoimmune hypothyroidism and proximal muscle weakness, which failed to respond to thyroxine. Subsequent electromyography and muscle biopsy confirmed polymyositis, which responded well to immunosuppressive therapy. She presented 4 months later with a thyroid carcinoma, most likely anaplastic, and died shortly afterwards. Although the association between malignancy and polymyositis remains controversial, to our knowledge this is the first report of thyroid carcinoma occuring in association with polymyositis and autoimmune hypothyroidism. [ABSTRACT FROM AUTHOR]

Delirium is a major disturbance in the mental state characterized by fluctuations in arousal, deficits in attention, distorted perception, and disruptions in memory and cognitive processing. Delirium affects approximately 18% to 25% of hospital inpatients, with even higher rates observed during critical illness. To develop therapies to shorten the duration and limit the adverse effects of delirium, it is important to understand the mechanisms underlying its presentation. Neuroimaging modalities such as magnetic resonance imaging (MRI), positron emission tomography, functional MRI, and near-infrared spectroscopy point to global atrophy, white matter changes, and disruptions in cerebral blood flow, oxygenation, metabolism, and connectivity as key correlates of delirium pathogenesis. Electroencephalography demonstrates generalized slowing of normal background activity, with pathologic decreases in variability of oscillatory patterns and disruptions in functional connectivity among specific brain regions. Elevated serum biomarkers of inflammation, including interleukin-6, C-reactive protein, and S100B, suggest a role of dysregulated inflammatory processes and cellular metabolism, particularly in perioperative and sepsis-related delirium. Emerging animal models that can mimic delirium-like clinical states will reveal further insights into delirium pathophysiology. The combination of clinical and basic science methods of exploring delirium shows great promise in elucidating its underlying mechanisms and revealing potential therapeutic targets., Competing Interests: None declared., (Thieme. All rights reserved.)

In this study, we explored the morphological and electrochemical properties of carbon-based electrodes derived from laser-induced graphene (LIG) and compared them to commercially available graphene-sheet screen-printed electrodes (GS-SPEs). By optimizing the laser parameters (average laser power, speed, and focus) using a design of experiments response surface (DoE-RS) approach, binder-free LIG electrodes were achieved in a single-step process. Traditional trial-and-error methods can be time-consuming and may not capture the interactions between all variables effectively. To address this, we focused on linear resistance and substrate delamination to streamline the DoE-RS optimization process. Two LIGs, designated LIG A and LIG B, were fabricated using distinct and optimized laser settings, which resulted in a sheet resistance of 25 ± 2 Ω/sq and 21 ± 1 Ω/sq, respectively. These LIGs, characterized by scanning electron microscopy, Raman spectroscopy, and contact angle analysis, exhibited a highly porous morphology with 13% pore coverage and a contact angle <50°, which significantly increased their hydrophilicity when compared to the GS-SPE. For the electrochemical studies, the oxidation of NO 2 - ion by the graphene-based working electrodes was investigated, as it allowed for the direct comparison of the LIGs to the GS-SPE. These included cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulsed voltammetry studies, which revealed that LIG electrodes displayed a remarkable 500% increase in peak current during NO 2 - oxidation compared to the GS-SPE. The LIGs also demonstrated improved stability and sensitivity (420 ± 30 and 570 ± 10 nAμM -1 cm -2 ) compared to the GS-SPE (73 ± 4 nAμM -1 cm -2 ) in the oxidation of NO 2 - ions; however, LIG B was more susceptible to ionic interference than LIG A. These findings highlight the value of applying statistical approaches such as DoE-RS to systematically improve the LIG fabrication process, enabling the rapid production of optimized LIGs that outperform conventional carbon-based electrodes.

The delivery of services to children with autism spectrum disorder (ASD) was disrupted during the coronavirus disease 2019 (COVID-19) pandemic, which may have affected child functioning and caregiver quality of life (QoL). This study examined changes in service intensity, child adaptive functioning, and caregiver QoL during the COVID-19 pandemic. Participants were 146 caregivers (87% mothers) of children with ASD (M age = 8.22 years; SD = 4.21) who were invited to complete an online survey about service intensity, child functioning, and caregiver QoL at four time points between the summer of 2020 and the summer of 2021. Simple regressions indicated that child adaptive functioning and caregiver QoL increased over time after stay-at-home orders were lifted. Fixed effects regression models indicated that increases in service intensity were associated with concurrent increases in caregiver physical QoL. Decreases in child repetitive behaviors were associated with concurrent increases in caregiver social and environmental QoL. These findings suggest that children and their caregivers demonstrated resilience in the year after stay-at-home orders were lifted. Additionally, service intensity and child repetitive behaviors may impact caregiver QoL, making these variables areas of opportunity for stakeholders and professionals., Competing Interests: Declarations. Conflict of Interest: No conflicts to declare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)