The Prevalence of Depression among patients and its detection by Primary Health Care Workers at Matawale Health Centre (Zomba)

Background Little information is available on the prevalence of depression in Malawi in primary health care settings and yet there is increased number of cases of depression presenting at tertiary level in severe form. Aim The aim of the study was to determine the prevalence of depression among patients and its detection by health care workers at a primary health care clinic in Zomba. Methods A cross-sectional survey was done among patients attending outpatient department at Matawale Health Centre, in Zomba from 1st July 2009 through to 31st July 2009. A total of 350 adults were randomly selected using systematic sampling. The “Self Reporting Questionnaire”, a questionnaire measuring social demographic factors and the Structured Clinical Interview for DSM-IV Axis I disorders Non-Patient Version (SCID-NP) were administered verbally to the participants. Findings The prevalence of depression among the patients attending the outpatients department was found to be 30.3% while detection rate of depression by clinician was 0%. Conclusion The results revealed the magnitude of depression which is prevalent in the primary health care clinic that goes undiagnosed and unmanaged. It is therefore recommended that primary health care providers do thorough assessments to address common mental disorders especially depression and they should be educated to recognise and manage depression appropriately at primary care level.

Metastability and dynamics of stem cells: from direct observations to inference at the single cell level

Organismal development, homeostasis, and pathology are rooted in inherently probabilistic events. From gene expression to cellular differentiation, rates and likelihoods shape the form and function of biology. Processes ranging from growth to cancer homeostasis to reprogramming of stem cells all require transitions between distinct phenotypic states, and these occur at defined rates. Therefore, measuring the fidelity and dynamics with which such transitions occur is central to understanding natural biological phenomena and is critical for therapeutic interventions.

While these processes may produce robust population-level behaviors, decisions are made by individual cells. In certain circumstances, these minuscule computing units effectively roll dice to determine their fate. And while the 'omics' era has provided vast amounts of data on what these populations are doing en masse, the behaviors of the underlying units of these processes get washed out in averages.

Therefore, in order to understand the behavior of a sample of cells, it is critical to reveal how its underlying components, or mixture of cells in distinct states, each contribute to the overall phenotype. As such, we must first define what states exist in the population, determine what controls the stability of these states, and measure in high dimensionality the dynamics with which these cells transition between states.

To address a specific example of this general problem, we investigate the heterogeneity and dynamics of mouse embryonic stem cells (mESCs). While a number of reports have identified particular genes in ES cells that switch between 'high' and 'low' metastable expression states in culture, it remains unclear how levels of many of these regulators combine to form states in transcriptional space. Using a method called single molecule mRNA fluorescent in situ hybridization (smFISH), we quantitatively measure and fit distributions of core pluripotency regulators in single cells, identifying a wide range of variabilities between genes, but each explained by a simple model of bursty transcription. From this data, we also observed that strongly bimodal genes appear to be co-expressed, effectively limiting the occupancy of transcriptional space to two primary states across genes studied here. However, these states also appear punctuated by the conditional expression of the most highly variable genes, potentially defining smaller substates of pluripotency.

Having defined the transcriptional states, we next asked what might control their stability or persistence. Surprisingly, we found that DNA methylation, a mark normally associated with irreversible developmental progression, was itself differentially regulated between these two primary states. Furthermore, both acute or chronic inhibition of DNA methyltransferase activity led to reduced heterogeneity among the population, suggesting that metastability can be modulated by this strong epigenetic mark.

Finally, because understanding the dynamics of state transitions is fundamental to a variety of biological problems, we sought to develop a high-throughput method for the identification of cellular trajectories without the need for cell-line engineering. We achieved this by combining cell-lineage information gathered from time-lapse microscopy with endpoint smFISH for measurements of final expression states. Applying a simple mathematical framework to these lineage-tree associated expression states enables the inference of dynamic transitions. We apply our novel approach in order to infer temporal sequences of events, quantitative switching rates, and network topology among a set of ESC states.

Taken together, we identify distinct expression states in ES cells, gain fundamental insight into how a strong epigenetic modifier enforces the stability of these states, and develop and apply a new method for the identification of cellular trajectories using scalable in situ readouts of cellular state.

Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-b during acute phase

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-a similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), high levels of circulating IFN-b were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN-b which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN-b in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

Impact of nurse-mediated management on achieving blood pressure goal levels in primary care: insights from the Valsartan intensified primary carE reduction of blood pressure study

BACKGROUND: Blood pressure targets in individuals treated for hypertension in primary care remain difficult to attain.

AIMS: To assess the role of practice nurses in facilitating intensive and structured management to achieve ideal BP levels.

METHODS: We analysed outcome data from the Valsartan Intensified Primary carE Reduction of Blood Pressure Study. Patients were randomly allocated (2:1) to the study intervention or usual care. Within both groups, a practice nurse mediated the management of blood pressure for 439 patients with endpoint blood pressure data (n=1492). Patient management was categorised as: standard usual care (n=348, 23.3%); practice nurse-mediated usual care (n=156, 10.5%); standard intervention (n=705, 47.3%) and practice nurse-mediated intervention (n=283, 19.0%). Blood pressure goal attainment at 26-week follow-up was then compared.

RESULTS: Mean age was 59.3±12.0 years and 62% were men. Baseline blood pressure was similar in practice nurse-mediated (usual care or intervention) and standard care management patients (150 ± 16/88 ± 11 vs. 150 ± 17/89 ± 11 mmHg, respectively). Practice nurse-mediated patients had a stricter blood pressure goal of ⩽125/75 mmHg (33.7% vs. 27.3%, p=0.026). Practice nurse-mediated intervention patients achieved the greatest blood pressure falls and the highest level of blood pressure goal attainment (39.2%) compared with standard intervention (35.0%), practice nurse-mediated usual care (32.1%) and standard usual care (25.3%; p<0.001). Practice nurse-mediated intervention patients were almost two-fold more likely to achieve their blood pressure goal compared with standard usual care patients (adjusted odds ratio 1.92, 95% confidence interval 1.32 to 2.78; p=0.001).

CONCLUSION: There is greater potential to achieve blood pressure targets in primary care with practice nurse-mediated hypertension management.

Primary tumor resection and overall survival in patients with metastatic colorectal cancer treated with palliative intent

The survival impact of primary tumor resection in patients with metastatic colorectal cancer (mCRC) treated with palliative intent remains uncertain. In the absence of randomized data, the objectives of the present study were to examine the effect of primary tumor resection (PTR) and major prognostic variables on overall survival (OS) of patients with de novo mCRC. Patients and Methods: Consecutive patients from the Australian 'Treatment of Recurrent and Advanced Colorectal Cancer' registry were examined from June 2009 to March 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to identify associations between multiple patient or clinical variables and OS. Patients with metachronous mCRC were excluded from the analyses. Results: A total of 690 patients de novo and 373 metachronous mCRC patients treated with palliative intent were identified. The median follow-up period was 30 months. The median age of de novo patients was 66 years; 57% were male; 77% had an Eastern Cooperative Oncology Group performance status of 0 to 1; and 76% had a colon primary. A total of 216 de novo mCRC patients treated with palliative intent underwent PTR at diagnosis and were more likely to have a colon primary (odds ratio [OR], 15.4), a lower carcinoembryonic antigen level (OR, 2.08), and peritoneal involvement (OR, 2.58; P < .001). On multivariate analysis, PTR at diagnosis in de novo patients was not associated with significantly improved OS (hazard ratio [HR], 0.82; 99% confidence interval [CI], 0.62-1.09; P = .068). PTR at diagnosis did not correlate with outcome in de novo patients with a colon primary (HR, 0.74; 99% CI, 0.54-1.01; P = .014) or a rectal primary (HR, 0.81; 99% CI, 0.27-2.44; P = .621). Conclusion: For de novo mCRC patients treated with palliative intent, PTR at diagnosis does not significantly improve OS when adjusting for known major prognostic factors. The outcomes of randomized trials examining the survival impact of PTR are awaited.

Rehabilitation staff perspectives on training for problem-solving therapy for primary care in a low vision service

Vision rehabilitation staff were trained to deliver problem-solving therapy for primary care (PSTPC) over the telephone to adults with depressive symptoms and low vision. Training was a 2-day workshop, completion of training cases, and assessment of treatment fidelity. Staff perspectives of training and challenges in PST-PC delivery were explored. Telephone-administered semistructured interviews were conducted pre- and post-workshop and following PST-PC competency. In all, 14 staff (mean age = 47.64 years, SD = 12.68 years, 93% females) achieved competency and 6 withdrew. Results showed an increased understanding of PST-PC from pre- to post-workshop (Z = −2.71, p = .007) and pre-workshop to post-competency (Z = −3.09, p = .002). A high level of satisfaction with training was reported. Staff challenges included the clients’ ability to define problems and brainstorm solutions. Training enabled staff to competently deliver PST-PC and may serve as a model for integrating depression care into vision rehabilitation services recommended by international guidelines.

The role of area-level deprivation and gender in participation in population-based faecal immunochemical test (FIT) colorectal cancer screening

This study aimed to investigate the effects of sex and deprivation on participation in a population-based faecal immunochemical test (FIT) colorectal cancer screening programme. The study population included 9785 individuals invited to participate in two rounds of a population-based biennial FIT-based screening programme, in a relatively deprived area of Dublin, Ireland. Explanatory variables included in the analysis were sex, deprivation category of area of residence and age (at end of screening). The primary outcome variable modelled was participation status in both rounds combined (with “participation” defined as having taken part in either or both rounds of screening). Poisson regression with a log link and robust error variance was used to estimate relative risks (RR) for participation. As a sensitivity analysis, data were stratified by screening round. In both the univariable and multivariable models deprivation was strongly associated with participation. Increasing affluence was associated with higher participation; participation was 26% higher in people resident in the most affluent compared to the most deprived areas (multivariable RR = 1.26: 95% CI 1.21–1.30). Participation was significantly lower in males (multivariable RR = 0.96: 95%CI 0.95–0.97) and generally increased with increasing age (trend per age group, multivariable RR = 1.02: 95%CI, 1.01–1.02). No significant interactions between the explanatory variables were found. The effects of deprivation and sex were similar by screening round. Deprivation and male gender are independently associated with lower uptake of population-based FIT colorectal cancer screening, even in a relatively deprived setting. Development of evidence-based interventions to increase uptake in these disadvantaged groups is urgently required.

Physiological and symptomatic responses to cycling and walking in intermittent claudication

To shed light on the potential efficacy of cycling as a testing modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle: brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) test after three familiarization tests on each mode. During each test, symptoms, oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (RER) and heart rate (HR) were measured, and for 10 min after each test the brachial and ankle systolic pressures were recorded. All but one subject experienced calf pain as the primary limiting symptom during T; whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea. Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs. 495 +/- 57 s), peak VO2, peak VE and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively correlated (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline in ankle pressures from resting values after C and T were not correlated with each other. These data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.