The introduction of proton pump inhibitors (PPIs) in the late 1980s optimised the medical treatment of acid-related disorders. They are potent medications and have a good safety profile. However, long-term therapy with PPIs may carry undesired side effects, one of which is hypomagnesaemia. This entity is likely to be under-reported. We present a clinical casewhich illustrates this important clinical problem. We present the case of a 73-year-old woman who was admitted to the hospital with supraventricular tachycardia due to hypomagnesaemia while using lansoprazole, followed by the literature review on this subject. In our patient after the intravenous magnesium replenishment, her arrhythmia resolved. After stopping her PPI her serum magnesium remained within reference values without oral supplementation. We believe that more attention towards this underdiagnosed side effect is required. Serum magnesium concentration should be checked in patients on PPIs if they are unwell or present with arrythmia.
We develop a new approach for estimating the undiagnosed fraction of HIV cases, the first step in the HIV Care Cascade. The goal is to address a critical blindspot in HIV prevention and treatment planning, with an approach that simplifies data requirements and can be implemented with open-source software. The primary data required is HIV testing history information on newly diagnosed cases. Two methods are presented and compared. The first is a general methodology based on simplified back-calculation that can be used to assess changes in the undiagnosed fraction over time. The second makes an assumption of constant incidence, allowing the estimate to be expressed as a simple closed formula calculation. We demonstrate the methods with an application to HIV diagnoses among men who have sex with men (MSM) from Seattle/King County. The estimates suggest that 6% of HIV-infected MSM in King County are undiagnosed, about one-third of the comparable national estimate. A sensitivity analysis on the key distributional assumption gives an upper bound of 11%. The undiagnosed fraction varies by race/ethnicity, with estimates of 4.9% among white, 8.6% of African American, and 9.3% of Hispanic HIV-infected MSM being undiagnosed.
To determine whether late-onset schizophrenia (LOS, onset after age 40) should be considered a distinct subtype of schizophrenia.
Participants included 359 normal comparison subjects (NCs) and 854 schizophrenia outpatients age > 40 (110 LOS, 744 early-onset schizophrenia or EOS). Assessments included standardized measures of psychopathology, neurocognition, and functioning.
EOS and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests. EOS and LOS groups had similar education, severity of depressive, negative, and deficit symptoms, crystallized knowledge, and auditory working memory, but LOS patients included more women and married individuals, had less severe positive symptoms and general psychopathology, and better processing speed, abstraction, verbal memory, and everyday functioning, and were on lower antipsychotic doses. Most EOS-LOS differences remained significant after adjusting for age, gender, severity of negative or deficit symptoms, and duration of illness.
LOS should be considered a subtype of schizophrenia.
Schizophrenia; aging; cognition; negative symptoms; quality of life; positive symptoms
It remains unclear how augmenting anti-psychotic medications with anti-depressants impacts primary positive and negative symptoms of schizophrenia. In this study, we used data collected from a randomized trial comparing citalopram to placebo for management of subsyndromal depression (SSD) in schizophrenia and schizoaffective disorder, to assess the effects of antidepressant augmentation on positive and negative symptoms.
Materials and Methods:
Participants in this study conducted at the University of California, San Diego and the University of Cincinnati, were persons with schizophrenia or schizoaffective disorder aged 40 or older and who met study criteria for SSD. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current anti-psychotic medication. Analysis of covariance was used to compare changes in positive and negative syndrome scale (PANSS) scores between treatment groups. We also assessed mediating effects of improvement in depression and moderating effects of multiple factors on positive and negative symptoms.
There was significant improvement in PANSS negative symptoms scores in the citalopram group, which was partially mediated by improvement in depressive symptoms. There was no effect on PANSS positive scores.
In patients with schizophrenia/schizoaffective disorder, treating depressive symptoms with citalopram appears to carry the added benefit of improving negative symptoms.
Citalopram; depression; negative symptom; schizophrenia
The quality of life (QOL) for individuals with schizophrenia is determined by a number of factors, not limited to symptomatology. The current study examined lack of insight as one such factor that may influence subjective QOL or functional capacity. It was hypothesized that insight would significantly interact with symptom severity to influence subjective QOL. Insight was not expected to influence the relation between symptom severity and functional capacity.
Participants were middle-aged and older outpatients who met diagnostic criteria for schizophrenia or schizoaffective disorder, and subsyndromal depression. Insight, psychopathology, and subjective QOL were assessed via semi-structured interviews and functional capacity was assessed via performance-based measures.
Insight interacts with negative symptom severity to predict subjective QOL. Severity of negative symptoms and insight contribute directly to functional capacity.
Individuals with intact insight may be better able to manage their symptoms, resulting in improved QOL. Treatment implications for improving the QOL of middle age and older adults with schizophrenia are discussed.
schizophrenia; insight; quality of life
The role of spirituality in the context of mental health and successful aging is not well understood. In a sample of community-dwelling older women enrolled at the San Diego site of the Women's Health Initiative study, we examined the association between spirituality and a range of variables associated with successful cognitive and emotional aging, including optimism, resilience, depression, and health-related quality of life (HRQoL).
A detailed cross-sectional survey questionnaire on successful aging was completed by 1,973 older women. It included multiple self-reported measures of positive psychological functioning (e.g., resilience, optimism,), as well as depression and HRQoL. Spirituality was measured using a 5-item self report scale constructed using two items from the Brief Multidimensional Measure of Religiosity/Spirituality and three items from Hoge's Intrinsic Religious Motivation Scale
Overall, 40% women reported regular attendance in organized religious practice, and 53% reported engaging in private spiritual practices. Several variables were significantly related to spirituality in bivariate associations; however, using model testing, spirituality was significantly associated only with higher resilience, lower income, lower education, and lower likelihood of being in a marital or committed relationship.
Our findings point to a role for spirituality in promoting resilience to stressors, possibly to a greater degree in persons with lower income and education level. Future longitudinal studies are needed to confirm these associations.
Spirituality; religiosity; elderly; successful aging; resilience
Depressive symptoms are common in middle aged and older patients with schizophrenia, The authors hypothesized that worse functioning in these patients would be associated with worse psychopathology.
Outpatients with schizophrenia were ≥40 years old with subsyndromal depression and Hamilton Depression Rating Scale Scores of ≥8. Exclusions were dementia, two months of either mania or major depression or 1 month active substance abuse/dependence. The authors administered performance based functional assessments, the Positive and Negative Syndrome Scale of Schizophrenia [PANSS], and Calgary Depression Rating Scale.
PANSS (−) scores were negatively correlated with the UCSD Performance Skills Based Assessment, Social Skills Performance Assessment and Medication Management Ability Assessment total error (MMAA) scores. Digit symbol scores served as a moderator of the relationship between MMAA and PANSS (−) scores.
Negative symptoms were associated with functioning. The relationship between negative symptoms and medication etrors seem to weaken in subjects with quicker processing speed.
Schizophrenia; functioning; psychopathology; negative symptoms
The authors hypothesized that age would moderate the response of patients with schizophrenia and subsyndromal depression (SSD) treated citalopram with depressive symptoms and other outcomes. Also, older patients would exhibit more side effects with citalopram.
Participants of 40 years or older had schizophrenia or schizoaffective disorder with SSD. Patients randomly received flexible dosing of citalopram or placebo augmentation of their antipsychotic medication. Linear regression determined whether age had any moderating effect on depressive symptoms, global psychopathology, negative symptoms, mental functioning, and quality of life. Age-related side effects were examined.
There were no significant drug group by age interaction in depressive or psychotic symptoms, mental Short Form-12, or quality of life scores. Similarly, there were few age-related side effect differences.
Symptoms in younger and older patients with schizophrenia and SSD treated with citalopram seem to respond similarly. Adverse events do not seem to differ with age.
Schizophrenia; age differences; citalopram; depression; psychopathology; quality of life
Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. SSRI’s appear to be helpful in alleviating depressive symptoms in patients with schizophrenia who have SSD in patients age 40 and greater. It is not known whether SSRI’s help improve functioning in this population. We hypothesized that treating this population with the SSRI citalopram would lead to improvements in social, mental and physical functioning as well as improvements in medication management and quality of life.
Participants were 198 adults ≥ 40 years old with schizophrenia or schizoaffective disorder who met study criteria for subsyndromal depression based on having two or more of the nine DSM-IV symptoms of a major depressive episode, for at least 2 weeks, and a Hamilton depression rating scale (HAM-D 17) score ≥ 8. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current antipsychotic medication(s) which was stable for 1 month. Subjects were assessed with the following functional scales at baseline and at the end of the 12-week trial: (1) social skills performance assessment (SSPA), (2) medication management ability assessment (MMAA), (3) mental and physical components of the medical outcomes study SF-12 Scale, and (4) the Heinrichs quality of life scale (QOLS). Analysis of covariance (ANCOVA) was used to compare differences between endpoint scores of the citalopram and placebo treated groups, controlling for site and baseline scores. ANCOVAs were also used to compare differences in the above endpoint scores in responders versus non-responders (responders = those with > 50% reduction in depressive symptoms).
Overall, the citalopram group had significantly higher SSPA, mental functioning SF-12, and quality of life scale (QOLS) scores compared to the placebo group. There was no effect on MMAA or physical functioning SF-12 scores. Responders had significantly better endpoint mental SF-12 and QOLS scores compared to non-responders. Response to citalopram in terms of depressive symptoms mediated the effect of citalopram on mental functioning, but not on the quality of life.
Citalopram augmentation of antipsychotic treatment in middle aged and older patients with schizophrenia and subsyndromal depression appears to improve social and mental health functioning as well as quality of life. Thus it is important for clinicians to monitor these aspects of functioning when treating this population of patients with schizophrenia with SSRI agents.
schizophrenia; citalopram; depression; functioning; social skills
Efforts to identify differential or core cognitive deficits in schizophrenia have been made for several decades, with limited success. Part of the difficulty in establishing a cognitive profile in schizophrenia is the considerable inter-patient heterogeneity in the level of cognitive impairment associated with this condition. Thus, it may be useful to examine the presence of relative cognitive weaknesses on an intra-patient level. In the present study we examined the rates of significant intra-person differences between crystallized verbal ability versus five other cognitive abilities among 127 persons with schizophrenia or schizoaffective disorder and 127 demographically matched normal comparison (NC) subjects. We found that the rates of significant discrepancies above the NC group base-rates was significantly greater in reference to those discrepancies involving visual memory relative to those associated with auditory memory, working memory, processing speed, and perceptual organization. The findings conflict with prior suggestions that working memory or auditory episodic memory are differential or core deficits in schizophrenia, and highlight the importance of considering visual memory in characterizing the cognitive effects of this condition.
psychosis; neuropsychology; neurocognitive; heterogeneity; idiographic
Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.
bioethics; mental competency; informed consent; multimedia learning; cognition disorders; schizophrenia
Objective: Providing incentives for research participation is widely practiced but minimally studied. In schizophrenia research, questions about capacity to consent and potential vulnerability may raise concerns when offering incentives for participation. Despite empirical attention focused on consent and decision-making capacity in schizophrenia, the issue of incentives has been essentially ignored. We examined willingness to participate in research, in relation to perceived risks and benefits, among people with schizophrenia and schizoaffective disorder. Method: Forty-six people with schizophrenia or schizoaffective disorder rated perceived risks and benefits of 5 hypothetical research vignettes. They also indicated whether they would be willing to participate at each of 5 incentive levels (including no compensation). Cognition was assessed with Mattis Dementia Rating Scale. Results: Ratings of risk and potential personal benefit were inversely correlated. For all scenarios, significant correlations were found between perceived risk and willingness to participate for greater compensation. Conversely, lower perceived likelihood of benefit was associated with a higher compensation threshold for participation in each scenario. Even at the highest proffered payment level for each scenario, however, a substantial proportion of respondents were not willing to participate. Risk assessment and willingness to participate (at all levels of compensation) were not associated with demographic variables or cognitive status. Conclusions: Determining whether incentives impede voluntarism remains an important task for empirical ethics research. Assessing potential research participants’ understanding and perceptions of risks, benefits, and alternatives to participation will help ensure that informed consent fulfills its mission—embodying the ethical principle of respect for persons.
ethics; informed consent; research participation; incentives; risk perception; voluntarism
Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFE C282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma is uncertain. We have carried out a cross-sectional study to determine the proportion of diagnosed hepatocellular carcinoma patients who are homozygous for the HFE C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia.
Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for HFE C282Y mutations; the data produced were compared with the frequency of HFE mutations in a large sample of the local population. Data were also retrieved from the East Anglian Cancer Intelligence Unit to determine the annual incidence of hepatocellular carcinoma; and from appropriate life tables.
Eight out of 144 of the cases were homozygous for the HFE C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male HFE C282Y homozygotes were more likely to be diagnosed with hepatocellular carcinoma (odds ratio [OR] = 14, 95% confidence interval [CI] = 5–37). For this population, we estimate that the penetrance of the HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females.
In this population, we found that only a very small proportion of homozygotes for the HFE C282Y mutation developed hepatocellular carcinoma. However, individuals with this genotype have a significantly increased risk of this rare disease relative to those who do not carry the mutations.