The Ethics of Algorithms in Healthcare.

The amount of data available to healthcare practitioners is growing, and the rapid increase in available patient data is becoming a problem for healthcare practitioners, as they are often unable to fully survey and process the data relevant for the treatment or care of a patient. Consequently, there are currently several efforts to develop systems that can aid healthcare practitioners with reading and processing patient data and, in this way, provide them with a better foundation for decision-making about the treatment and care of patients. There are also efforts to develop algorithms that provide suggestions for such decisions. However, the development of these systems and algorithms raises several concerns related to the privacy of patients, the patient-practitioner relationship, and the autonomy of healthcare practitioners. The aim of this article is to provide a foundation for understanding the ethical challenges related to the development of a specific form of data-processing systems, namely clinical algorithms.

Validation study of the early onset schizophrenia diagnosis in the Danish Psychiatric Central Research Register.

The objective of this study is to assess (1) the concordance and validity of schizophrenia register diagnoses among children and adolescents (early onset schizophrenia = EOS) in the Danish Psychiatric Central Research Register (DPCRR), and (2) the validity of clinical record schizophrenia diagnoses. Psychiatric records from 200 patients with a first-time diagnosis of schizophrenia (F20.x) at age < 18 years between 1994 and 2009 in the DPCRR were rated by experienced clinicians according to ICD-10 criteria, using a predefined checklist. We retrieved 178 records, representing 19.6% of all patients diagnosed with EOS from 1994 to 2009. Mean age was 15.2 years and 56.2% were males. The register-based and clinical diagnoses matched in 158 cases (88.8%). Raters' diagnoses confirmed the DPCRR schizophrenia diagnoses in 134 cases, rendering a diagnostic validity of 75.3% of DPCRR schizophrenia, while 149 cases were confirmed as being in the schizophrenia spectrum (83.7%). When removing records with registration errors, 83.5% of cases were confirmed as schizophrenia and 91.8% as being in the schizophrenia spectrum. Interrater reliability was substantial with Cohen's kappa > 0.78-0.83 depending on classification. Compared to diagnoses made in outpatient settings, EOS diagnoses during hospitalizations were more likely to be valid and had fewer registration errors. Diagnosed in inpatient settings, EOS diagnoses are reliable and valid for register-based research. Schizophrenia diagnosed in children and adolescents in outpatient settings were found to have a high number of false-positives, both due to registration errors and diagnostic practice. Utilizing this knowledge, it is possible to reduce the number of false-positives in register-based research of EOS.

Profile of cognitive deficits and associations with depressive symptoms and intelligence in chronic early-onset schizophrenia patients.

Cognitive deficits in several domains have been demonstrated in early-onset schizophrenia patients but their profile and relation to depressive symptoms and intelligence need further characterization. The purpose was to characterize the profile of cognitive deficits in chronic, early-onset schizophrenia patients, assess the potential associations with depressive symptom severity, and examine whether cognitive deficits within several domains reflect intelligence impairments. This study compared attention, visual-construction, aspects of visual and verbal memory, and executive functions in chronic, early-onset schizophrenia patients (mean age = 20.7 years) (N = 18) and healthy controls (N = 38). Schizophrenia diagnoses were established at the time of the patients' first clinical presentation during childhood or adolescence and were confirmed five years later. In the chronic phase of early-onset schizophrenia, significant deficits were observed in all specific cognitive functions. The profile of cognitive deficits was jagged, and visual-construction, attention, and one aspect of verbal memory (verbal stories recall) were differentially impaired. Deficits of visual recall, visual recognition, and executive functions were accounted for by deficits in intelligence, while this was not the case for deficits of verbal recall of stories or attention. No significant associations were observed between the severity of cognitive deficits and that of depressive symptoms. Chronic, early-onset schizophrenia is characterized by a broad and jagged profile of cognitive deficits. Deficits of attention and verbal recall of stories appear not to be accounted for by deficits in intelligence, and the severity of cognitive deficits seems independent from that of depressive symptoms.

Attitudes of Patients and Health Professionals Regarding Screening Algorithms: Qualitative Study.

BACKGROUND: As a preamble to an attempt to develop a tool that can aid health professionals at hospitals in identifying whether the patient may have an alcohol abuse problem, this study investigates opinions and attitudes among both health professionals and patients about using patient data from electronic health records (EHRs) in an algorithm screening for alcohol problems. OBJECTIVE: The aim of this study was to investigate the attitudes and opinions of patients and health professionals at hospitals regarding the use of previously collected data in developing and implementing an algorithmic helping tool in EHR for screening inexpedient alcohol habits; in addition, the study aims to analyze how patients would feel about asking and being asked about alcohol by staff, based on a notification in the EHR from such a tool. METHODS: Using semistructured interviews, we interviewed 9 health professionals and 5 patients to explore their opinions and attitudes about an algorithm-based helping tool and about asking and being asked about alcohol usage when being given a reminder from this type of tool. The data were analyzed using an ad hoc method consistent with a close reading and meaning condensing. RESULTS: The health professionals were both positive and negative about a helping tool grounded in algorithms. They were optimistic about the potential of such a tool to save some time by providing a quick overview if it was easy to use but, on the negative side, noted that this type of helping tool might take away the professionals' instinct. The patients were overall positive about the helping tool, stating that they would find this tool beneficial for preventive care. Some of the patients expressed concerns that the information provided by the tool could be misused. CONCLUSIONS: When developing and implementing an algorithmic helping tool, the following aspects should be considered: (1) making the helping tool as transparent in its recommendations as possible, avoiding black boxing, and ensuring room for professional discretion in clinical decision making; and (2) including and taking into account the attitudes and opinions of patients and health professionals in the design and development process of such an algorithmic helping tool.

Deficient maturation of aspects of attention and executive functions in early onset schizophrenia.

The few existing long-term, neuropsychological follow-up studies of early onset schizophrenia (EOS) patients have reported relative stability in some cognitive functions but abnormal developmental trajectories in verbal memory, set shifting, aspects of attention, and speed of information processing throughout late adolescence into early adulthood. The current 5-year follow-up study compared the development of specific cognitive functions in EOS patients (N = 17) from the time of first-episode to chronic phase with that of healthy controls (N = 38) and secondarily to patients with other early onset, non-organic, non-affective psychoses (EOP) (N = 11). Speed of processing of executive functions, set shifting, and attention improved significantly in the healthy controls and reflected continuous functional maturation during late adolescence and early adulthood. The developmental progression of attention and set shifting but not speed of processing of executive functions was significantly subnormal in EOS patients. Other specific cognitive functions that had attained functional maturity in the healthy controls before or around the time of the baseline assessment showed normal development in EOS patients during the follow-up period, indicating stable cognitive deficits. These results suggest post-onset developmental deficits in two out of the three aspects of attention and executive functions that have protracted maturational trajectories and that overlap the age of onset of EOS. No significant difference in the development of any specific cognitive function was found between the EOS and EOP group.

Course of intelligence deficits in early onset, first episode schizophrenia: a controlled, 5-year longitudinal study.

Only few prospective longitudinal studies have assessed the course of intelligence deficits in early onset schizophrenia (EOS), and these have used different age appropriate versions of Wechsler Intelligence Scales and age appropriate norms. The post-psychotic development of intelligence in EOS has predominantly been characterized as relatively stable in these studies. However, comparisons of IQs from different test versions based on the different norms may not permit unequivocal interpretations. The objective of the current study was to compare the development of intelligence in EOS patients (N = 10) from their first psychotic episode to 5 years of post onset with that of healthy controls (N = 35) and patients who at baseline had been diagnosed with other non-affective psychoses (N = 8). The same version of a Wechsler Intelligence Scale was administered at both baseline and follow-up assessments, and the same norms were used to derive IQs at baseline and follow-up. Significantly smaller change in mean full scale intelligence quotient (FSIQ) was found in diagnostically stable EOS patients compared with healthy controls during the follow-up period. However, no statistically significant difference in mean FSIQ change was observed between patients with EOS and patients with other non-affective psychoses, although this result must be interpreted with caution due to the small sample sizes. The results suggest abnormally slow acquisition of new intellectual information and skills in EOS patients during the first 5 years after full clinical presentation.

The effects of polyphenols in olive leaves on platelet function.

INTRODUCTION: The phenolic compounds of olive leaves and olive oils in the Mediterranean diet have been associated with a reduced incidence of heart disease. Accordingly, antioxidant-rich diets may prevent the deleterious effects of oxidative metabolism by scavenging free radicals, thus inhibiting oxidation and delaying atherosclerosis. The process involves phospholipase C activation and arachidonic acid metabolism, and is thought to reduce hydrogen peroxide (H(2)O(2)). In our study, an extract of Olea europaea L. leaves was used. The active phenolic compounds in this extract are part of the secoiridoid family, known for their capacity to scavenge H(2)O(2). The results from this study will help to improve our understanding of effects of polyphenol antioxidants in olive leaf extract on platelet function. METHODS: Full blood examination (FBE), platelet aggregation, and ATP release were performed on samples from fasting, normal, healthy male subjects. Platelet function at increasing concentrations of oleuropein was investigated through measures of platelet aggregation and ATP release from activated platelets. RESULTS: Blood analysis (n=11) revealed a significant dose-dependant reduction in platelet activity with olive extract concentrations of 1.0% v/v (P<0.001). ATP Release showed a similar pattern (P=0.02). CONCLUSIONS: Olive leaf polyphenols derived from O. europaea L. leaves inhibited in vitro platelet activation in healthy, non-smoking males. Further bioavailability studies need to be undertaken to determine the in vivo effect of extract on platelet function and to validate the present results.

Soluble Mediators in Platelet Concentrates Modulate Dendritic Cell Inflammatory Responses in an Experimental Model of Transfusion.

The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1ß and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1ß, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1ß significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.

Are there better Bcr-Abl kinase inhibitors for chronic myeloid leukaemia than imatinib? Evaluation of Saglio G, Kim D-W, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9, and Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-70.

The Bcr-Abl kinase inhibitor imatinib is the standard treatment for chronic myeloid leukaemia (CML). Some subjects with CML do not respond to, or are intolerant of, imatinib. Nilotinib and dasatinib were initially developed to treat these subjects, and were shown to be effective. They are now being trialled as initial 'inib' treatment for CML. The objective was to evaluate the recent Phase III clinical trials comparing nilotinib or dasatinib with imatinib in newly diagnosed CML. Nilotinib and dasatinib were shown to give a higher rate of complete cytogenic and major molecular responses than imatinib over 1 year. They should be considered as first choice in the treatment of subjects who develop CML. However, there are still major limitations to the populations with which these 'inib' drugs can be used, and how they can be used.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective of this review was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. There is no clear-cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis but it does cause adverse effects. It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.