Drivers for change in primary care of diabetes following a protected learning time educational event: interview study of practitioners

Background: A number of protected learning time schemes have been set up in primary care across the United Kingdom but there has been little published evidence of their impact on processes of care. We undertook a qualitative study to investigate the perceptions of practitioners involved in a specific educational intervention in diabetes as part of a protected learning time scheme for primary health care teams, relating to changing processes of diabetes care in general practice. Methods: We undertook semistructured interviews of key informants from a sample of practices stratified according to the extent they had changed behaviour in prescribing of ramipril and diabetes care more generally, following a specific educational intervention in Lincolnshire, United Kingdom. Interviews sought information on facilitators and barriers to change in organisational behaviour for the care of diabetes. Results: An interprofessional protected learning time scheme event was perceived by some but not all participants as bringing about changes in processes for diabetes care. Participants cited examples of change introduced partly as a result of the educational session. This included using ACE inhibitors as first line for patients with diabetes who developed hypertension, increased use of aspirin, switching patients to glitazones, and conversion to insulin either directly or by referral to secondary care. Other reported factors for change, unrelated to the educational intervention, included financially driven performance targets, research evidence and national guidance. Facilitators for change linked to the educational session were peer support and teamworking supported by audit and comparative feedback. Conclusion: This study has shown how a protected learning time scheme, using interprofessional learning, local opinion leaders and early implementers as change agents may have influenced changes in systems of diabetes care in selected practices but also how other confounding factors played an important part in changes that occurred in practice

How effective are Z-drug hypnotics for treatment of adult insomnia? Meta-analysis of data submitted to the Food and Drug Administration

The Problem: Z-drugs are the most commonly prescribed hypnotics worldwide. They are widely prescribed because general practitioners and patients believe that they are effective and superior to older hypnotics. Previous meta-analyses of Z-drugs suffer from publication or reporting bias and did not adequately examine study heterogeneity. We wanted to investigate the effectiveness of Z-drugs in adults using a data source that was less likely to be affected by publication bias. The approach: We examined clinical trials of currently approved Z-drugs submitted to the Food and Drug Administration (FDA) since pharmaceutical companies are required to provide information on all sponsored trials, whether published or not, when applying for new drug approvals. We included randomized double blind placebo controlled trials and excluded studies with a crossover design, those including healthy patients with normal sleep or single night studies with induced insomnia. We analysed drug efficacy as change score from baseline to posttest for drug and placebo groups, and the difference of both change scores for available outcomes. Weighted raw and standardized mean differences with their confidence intervals (CIs) under random-effects assumptions were calculated for polysomnographic (PSG) and subjective outcomes: wake after sleep onset, sleep latency, number of awakenings, total sleep time, sleep efficiency, subjective sleep quality, and morning sleepiness score. We performed weighted regression moderator analysis to explain heterogeneity of drug effects. Findings: We included 16 studies comprising 4973 subjects from different countries, varying drug dosages, treatment lengths and study years. Z-drugs showed significant but small improvements (reductions) only in PSG (d+ = -0.36, 95% CI = -0.57 to -0.16) and subjective sleep latency (d+ = -0.33, 95% CI = -0.62 to -0.041) compared with placebo. Analyses of weighted mean raw differences indicated that drugs decreased sleep latency by only 22 minutes (95% CI = -33 TO -11) with no evidence of change in other measures. Moderator analyses indicated that sleep latency was more likely to be reduced with larger drug doses, studies published earlier, including higher proportions of younger or women patients, and of longer treatment duration. Consequences: This study of FDA data shows that, despite being commonly prescribed, Z-drugs have limited benefit with small reductions in subjective and PSG sleep latency especially with larger dosages, but no improvement in other sleep measures compared to placebo. Placebo effects were moderate for sleep latency. Doctors and patients need to be aware of the relative benefits as well as harms of hypnotic drugs when deciding to use them in preference to psychological treatments

The use of segmented regression in analysing interrupted time series studies : an example in pre-hospital ambulance care

Peer reviewedPublisher PD

Habitat-use influences severe disease-mediated population declines in two of the most common garden bird species in Great Britain

The influence of supplementary feeding of wildlife on disease transmission and its consequent impacts on population dynamics are underappreciated. In Great Britain, supplementary feeding is hypothesised to have enabled the spread of the protozoan parasite, Trichomonas gallinae, from columbids to finches, leading to epidemic finch trichomonosis and a rapid population decline of greenfinch (Chloris chloris). More recently, chaffinch (Fringilla coelebs), has also declined markedly from the second to fifth commonest bird in Britain. Using citizen science data, we show that both declines were driven primarily by reduced adult survival, with the greatest reductions occurring in peri-domestic habitats, where supplementary food provision is common. Post-mortem examinations showed a proportional increase in chaffinch trichomonosis cases, near-contemporaneous with its population decline. Like greenfinches, chaffinches often use supplementary food, but are less associated with human habitation. Our results support the hypothesis that supplementary feeding can increase parasite transmission frequency within and between common species. However, the dynamics behind resultant population change can vary markedly, highlighting the need for integrating disease surveillance with demographic monitoring. Other species susceptible to T. gallinae infection may also be at risk. Supplementary feeding guidelines for wildlife should include disease mitigation strategies to ensure that benefits to target species outweigh risks

VEGF-C is associated with lymphatic status and invasion in oral cancer

Background: Nodal metastasis is a major prognostic indicator for oral squamous cell carcinoma (OSCC) progression. Recently, it has been revealed that lymphangiogenic growth factor VEGF-C and its receptor Flt-4 play an important role for invasion and metastasis in cancer cells. Aim: To examine VEGF-C expression and its correlation with lymphatic status, including the number of lymph vessels and lymphatic invasion, tumour invasion and metastasis in OSCC. Methods: Intratumoural and peritumoural lymphatic vessels were examined using D2-40 in 54 OSCC cases and correlated with VEGF-C expression and clinicopathological findings. The histological pattern of invasion and pathological findings were compared. Results: High expression of VEGF-C was frequently observed in OSCC and was associated with increased number of lymph vessels and lymphatic invasion. VEGF-C was well correlated with invasion pattern and metastasis. Conclusions: Results suggest that VEGF-C may play an important role for lymphangiogenesis and invasion in the metastatic process and can be a strong predicting factor for metastasis of OSCC

Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma : A Review

It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC

A study of lipid profile and glycemic status in patients with chronic kidney disease of unknown etiology in Sri Lanka

Background: Dyslipidemia and impaired glucose tolerance are common complications of chronic kidney disease (CKD) and are responsible for increased cardiovascular risk. Studies on lipid profile and glycemic status in CKD of unknown origin (CKDu) are scarce. The objective of this study was to evaluate the lipid profile and glycemic status of the patients with CKDu and to aid in preventing morbidity and mortality.Methods: The descriptive, cross sectional study was conducted in a rural CKDu endemic area, Girandurukotte.  Data was collected from February 2018 to June 2019. For the diagnosis of CKDu, history and clinical features with supportive biochemical, renal biopsy and radiological evidence were taken as criteria. Blood samples were taken for serum creatinine, lipid profile and HbA1C. Already diagnosed patients with diabetes mellitus and dyslipidemia were excluded.Results: A total of 168 patients within the age range of 32-66 years (mean 50.3±7.7) were participated. There were 106 males (63%) 46.4% were farmers. Majority of the patients (65.5%) had normal body mass index (BMI) (mean 22.9 kg/m2, normal range 18.5-23.5%) followed by overweight (23.5-30 kg/m2) in 55 (32.7%) patients. The prevalence of dyslipidemia in CKDu was found to be 55.9%.  Majority of the abnormality was seen in the HDL group with 68 (40.5%) patients having low HDL cholesterol (mean 44.7 mg/dl, SD=12.3).  There was a significant rise in the serum triglyceride concentration (>150 mg/dl) in 53 (31.5%) (mean 152.4 mg/dl, SD=73.5) and total cholesterol (>200 mg/dl) in 30 (18%) patients (mean 182 mg/dl, SD=36.9). LDL cholesterol abnormality (>130 mg/dl) was seen in only 9 patients (mean 88.7 7658mg/dl, SD=25.4). From the total, 144 (85.7%) patients had abnormal HbA1C levels; 27 (16.1%) patients had HbA1C levels between 5.7% and 6.4% (pre-diabetes), and 117 (69.6%) patients had HbA1C level more than 6.5% (diabetes mellitus). There was no statistically significant association between HbA1C levels and BMI (p=0.29) or HbA1C and lipid abnormalities (p=0.32)Conclusions: The high prevalence of dyslipidemia, pre-diabetes and diabetes mellitus in patients with CKDu may accelerate the progression of chronic kidney disease and increase the risk of cardiovascular disease. Early detection, initiation of appropriate medication and early referral to the expertise will ameliorate morbidity and mortality.

Periostin Promotes Tumor Lymphangiogenesis

Background: Metastasis to regional lymph nodes via lymphatic vessels plays a key role in cancer progression. Tumor lymphangiogenesis is known to promote lymphatic metastasis, and vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis during the process of metastasis. We previously identified periostin as an invasion- and angiogenesis-promoting factor in head and neck squamous cell carcinoma (HNSCC). In this study, we discovered a novel role for periostin in tumor lymphangiogenesis. Methods and Findings: Periostin overexpression upregulated VEGF-C mRNA expression in HNSCC cells. By using conditioned media from periostin-overexpressing HNSCC cells, we examined tube formation of lymphatic endothelial cells. Conditioned media from periostin-overexpressing cells promoted tube formation. To know the correlation between periostin and VEGF-C, we compared Periostin expression with VEGF-C expression in 54 HNSCC cases by immunohistochemistry. Periostin expression was correlated well with VEGF-C expression in HNSCC cases. Moreover, correlation between periostin and VEGF-C secretion was observed in serum from HNSCC patients. Interestingly, periostin itself promoted tube formation of lymphatic endothelial cells independently of VEGF-C. Periostin-promoted lymphangiogenesis was mediated by Src and Akt activity. Indeed possible correlation between periostin and lymphatic status in periostin-overexpressing xenograft tumors and HNSCC cases was observed. Conclusions: Our findings suggest that periostin itself as well as periostin-induced upregulation of VEGF-C may promote lymphangiogenesis. We suggest that periostin may be a marker for prediction of malignant behaviors in HNSCC and a potential target for future therapeutic intervention to obstruct tumoral lymphatic invasion and lymphangiogenesis in HNSCC patients