Evaluating pancreatitis in primary care: a population-based cohort study

Background

Pancreatitis is an important condition with significant mortality. Primary care may have an important role to play in its prevention, early diagnosis, and ongoing management.

Aim

To evaluate incidence, case fatality, and clinical features of acute and chronic pancreatitis in a large population.

Design and setting

Population-based cohort study using a primary care database in the UK from 1990 to 2013.

Method

Use of general practice records from 16 491 patients diagnosed with pancreatitis. Age-standardised incidence rates and case fatality were estimated. Clinical features, aetiology, and patterns of recurrence were evaluated.

Results

Incidence of pancreatitis increased from 14.8 in 100 000 (1990–1994) to 31.2 in 100 000 (2010–2013) in males, and from 14.5 to 28.3 in 100 000 in females (2010–2013). Overall case fatality after diagnosis was 4.3% (95% CI = 4.0% to 4.6%) at 90 days and 7.9% (95% CI = 7.5% to 8.4%) at 365 days. In 1990–1994, 10% of patients with acute pancreatitis were recorded as heavy drinkers, increasing to 12% in 2010–2012; for patients with chronic pancreatitis the proportions were 13%, rising to 21%. Among patients who died in the 90 days after diagnosis, 92% consulted with their general practice in the 2 months before first diagnosis.

Conclusion

The incidence of pancreatitis is increasing over time. Alcohol abuse may now account for at least one in eight cases of acute, and one in five cases of chronic pancreatitis. Consultations among those who subsequently died may have offered potential for earlier diagnosis and intervention.     

Feasibility and potential role of ferumoxytol-enhanced neuroimaging in HIV-associated neurocognitive disorder

We assessed ferumoxytol-enhanced brain MRI to identify monocyte/macrophage accumulation in HIV-associated neurocognitive disorder (HAND). Four HIV-infected subjects with undetectable HIV RNA levels on antiretroviral therapy, HIV DNA level in CD14+ cells ≥10 copies/10⁶ cells, and cognitive impairment underwent ferumoxytol-enhanced brain MRI. On post-ferumoxytol susceptibility-weighted images, all HIV-infected subjects demonstrated a diffuse “tram track” appearance in the perivascular regions of cortical and deep white matter vessels suggesting ferumoxytol uptake in monocytes/macrophages. This finding was not present in an HIV-seronegative control. While ferumoxytol may have potential as an imaging biomarker for monocyte/macrophage accumulation in patients with HAND, future study is needed.     

Endoscopic Resection of Tuberculum Sellae Meningiomas

Objective To evaluate the results of endoscopic transnasal resection of tuberculum sellae meningiomas (TSMs) as compared with transcranial approaches.Design We retrospectively analyzed five patients who underwent endoscopic endonasal resection of TSM and performed a comprehensive review of articles published between 2000 and 2012 describing the operative treatment of TSMs.Results Gross total resection (GTR) was achieved in four patients (80%). Transient diabetes insipidus occurred in three patients (60%). Preoperative visual field deficit resolved in all patients. Cerebrospinal fluid (CSF) leak occurred in one patient. Analysis of published studies included 1,026 transcranial and 144 transnasal cases. GTR was achieved in 85% of transcranial and 72% of transnasal cases. Visual field deficit improved in 65% of transcranial and 82% of transnasal cases. Rate of diabetes insipidus and CSF leak was higher in the transnasal series. Rate of GTR and visual improvement was higher in endoscopic endonasal as compared with microsurgical transnasal series.Conclusion The literature supports transsphenoidal surgery for the resection of TSMs with significant optic nerve compromise and limited lateral extension. This approach may have an equivalent if not superior outcome over transcranial surgery in visual outcome. CSF leaks are still a challenge but may improve with the use of vascularized nasoseptal flaps.     

Vitamin D supplementation for treatment and prevention of pneumonia in under-five children: <Emphasis Type="Italic">A randomized double-blind placebo controlled trial</Emphasis>

Objective

To evaluate the efficacy of single oral mega-dose of Vitamin D3 for treatment and prevention of pneumonia in underfive children.

Design

Randomized, double blind, placebo-controlled trial.

Setting

Tertiary-care hospital.

Participants

324 children (of 980 assessed) between 6 mo-5 y age (median (IQR): 12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were vitamin D deficient (serum 25(OH)D <12 ng/mL).

Intervention

100,000 IU of oral cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at enrolment.

Outcome variables

Primary: Time to resolution of severe pneumonia and proportion of children having recurrence of pneumonia in next 6 months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and cathelicidin 2 weeks following supplementation; and time taken for overall resolution of illness.

Results

Median (95% CI) time for resolution of severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31 (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1·39 (1·11, 1·76); P=0·005]. The risk of recurrence of pneumonia in next 6 months was comparable in the two groups [placebo: 36/158 (22·8%); vitamin D: 39/156 (25%); RR (95% CI): 1·13 (0·67,1·90); P=0·69]. Proportion of vitamin D deficient children declined from 38% to 4% in the supplementation group, and from 41% to 33% in the placebo group, two weeks after supplementation. There was no significant effect of vitamin D supplementation on serum levels of cathelicidin, IgA and IgG. The time taken for complete recovery from pneumonia, duration of hospitalization, and fever clearance time were comparable for the two groups. No adverse event was noted related to the intervention.

Conclusion

There is no robust evidence of a definite biological benefit, either for therapy or prevention, to suggest a routine megadose supplement of vitamin D3 for under-five children with severe pneumonia.

     

Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed

Leishmania are protozoan parasites that cause a wide spectrum of clinical diseases in humans and are a major public health risk in several countries. Leishmania life cycle consists of an extracellular flagellated promastigote stage within the midgut of a sandfly vector, and a morphological distinct intracellular amastigote stage within macrophages of a mammalian host. This study reports the use of DNA oligonucleotide genome microarrays representing 8160 genes to analyze the mRNA expression profiles of L. major promastigotes and lesion derived amastigotes. Over 94% of the genes were expressed in both life stages. Advanced statistical analysis identified a surprisingly low degree of differential mRNA expression: 1.4% of the total genes in amastigotes and 1.5% in promastigotes. These microarray results demonstrate that the L. major genome is essentially constitutively expressed in both life stages and suggest that Leishmania is constitutively adapted for survival and replication in either the sandfly vector or macrophage host utilizing an appropriate set of genes for each vastly different environment. Quantitative proteomics, using the isotope coded affinity tag (ICAT) technology and mass spectrometry, was used to identify L. infantum promastigote and axenic amastigote differentially expressed proteins. Of the 91 distinct proteins identified, 8% were differentially expressed in the amastigote stage, 20% were differentially expressed in the promastigote stage, and the remaining 72% were considered constitutively expressed. The differential expression was validated by the identification of previously reported stage specific proteins and identified several amastigote and promastigote novel stage specific proteins.