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Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
This study uses stable carbon δ13C and oxygen δ18O isotope compositions data to assess the extent to which diet breadths of northwestern Guyana changed during the Holocene. We analyzed human bone and enamel remains from seven shell mound sites dating between 7500 and 2600 BP. Our analyses demonstrate some constancy in C3 plant availability during the past several thousand years, though we note increasing reliance on such plants beginning in the Early Holocene. We also document warming intervals during the Early Holocene (Early Archaic) that appear to correlate with dry periods known elsewhere in the central Amazon during this period.
Depression is a prevalent long-term condition that is associated with substantial resource use. Telehealth may offer a cost-effective means of supporting the management of people with depression.
To investigate the cost-effectiveness of a telehealth intervention (‘Healthlines’) for patients with depression.
A prospective patient-level economic evaluation conducted alongside a randomised controlled trial. Patients were recruited through primary care, and the intervention was delivered via a telehealth service. Participants with a confirmed diagnosis of depression and PHQ-9 score ≥10 were recruited from 43 English general practices. A series of up to 10 scripted, theory-led, telephone encounters with health information advisers supported participants to effect a behaviour change, use online resources, optimise medication and improve adherence. The intervention was delivered alongside usual care and was designed to support rather than duplicate primary care. Cost-effectiveness from a combined health and social care perspective was measured by net monetary benefit at the end of 12 months of follow-up, calculated from incremental cost and incremental quality-adjusted life years (QALYs). Cost–consequence analysis included cost of lost productivity, participant out-of-pocket expenditure and the clinical outcome.
A total of 609 participants were randomised – 307 to receive the Healthlines intervention plus usual care and 302 to receive usual care alone. Forty-five per cent of participants had missing quality of life data, 41% had missing cost data and 51% of participants had missing data on either cost or utility, or both. Multiple imputation was used for the base-case analysis. The intervention was associated with incremental mean per-patient National Health Service/personal social services cost of £168 (95% CI £43 to £294) and an incremental QALY gain of 0.001 (95% CI −0.023 to 0.026). The incremental cost-effectiveness ratio was £132 630. Net monetary benefit at a cost-effectiveness threshold of £20 000 was –£143 (95% CI –£164 to –£122) and the probability of the intervention being cost-effective at this threshold value was 0.30. Productivity costs were higher in the intervention arm, but out-of-pocket expenses were lower.
The Healthlines service was acceptable to patients as a means of condition management, and response to treatment after 4 months was higher for participants randomised to the intervention. However, the positive average intervention effect size was modest, and incremental costs were high relative to a small incremental QALY gain at 12 months. The intervention is not likely to be cost-effective in its current form.
Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences.
We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases.
The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms.
Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.
A baroreflex mechanism may explain hypertensive hypoalgesia.
At rest, arterial baroreceptors are stimulated during the systolic
upstroke of the pressure pulse wave. This study examined the
effects of naturally occurring variations in baroreceptor activity
during the cardiac cycle on an objective measure of pain, the
nociceptive flexion reflex (NFR). Two interleaved up–down
staircase procedures determined separate NFR thresholds during
systole and diastole in 36 healthy, normotensive young adults.
On odd-numbered trials, the sural nerve was stimulated
electrocutaneously at R + 300 ms whereas on even-numbered trials,
stimulation was delivered at R + 600 ms. The NFR threshold was
higher at R + 300 ms than R + 600 ms. In contrast, stimulus
intensity ratings did not differ between R + 300 ms and R +
600 ms. Stimulation of baroreceptors by natural increases in
blood pressure during the systolic phase of the cardiac cycle
was associated with dampened nociception.
Carotid baroreceptor stimulation has been shown to dampen
pain. This study tested, in 40 normotensive adults, the
hypothesis that pain is lower during systole when arterial
baroreceptor stimulation is maximal than diastole when
stimulation is minimal. The sural nerve was stimulated
electrocutaneously to obtain a nociceptive flexion reflex
(NFR) threshold, and then stimulation was delivered for
28 trials at 100% NFR threshold at seven intervals after
the R-wave. Nociceptive responding was indexed by electromyographic
(EMG) activity elicited in the biceps femoris. Significant
variations in EMG activity occurred across the cardiac
cycle, with less activity midcycle, indicating that the
NFR response was attenuated during systole compared to
diastole. Stimulation of baroreceptors by natural changes
in blood pressure during the cardiac cycle dampened nociception,
and accordingly, the data support the arterial baroreflex
mechanism of hypertensive hypoalgesia.
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