Citations

Objective: To expand the adverse events associated with metronidazole to include nonconvulsive status epilepticus (NCSE). Design: Observational single case report of a rare association. Setting: Hospitalized lung transplant recipient treated with metronidazole for prevention of infection. Patient: A 56-year-old man with systemic symptoms, peripheral neuropathy, generalized seizure, and a subsequent acute deterioration of mental status due to NCSE. Interventions: Administration of midazolam was successful in terminating status epilepticus. Main Outcome Measures: Abrupt termination of NCSE was evident on continuous bedside electroencephalogam associated with clinical resolution of mental status. Results: Recovery occurred from NCSE eventually deteriorating to a fatal outcome. Conclusions: Metronidazole may be associated with successfully treated NCSE.

Despite advances in evidence‐based treatments (EBTs), research suggests these interventions are not utilized in practice settings. This study examined implementation of multi‐family psychoeducational psychotherapy (MF‐PEP), an EBT for childhood mood disorders, in two outpatient community clinics. Fifteen community therapists facilitated MF‐PEP. Twenty community clinicians referred 40 children ages 8–12 with mood disorders and their parents who participated in MF‐PEP. Preliminary descriptive findings based on observations and self‐report questionnaires demonstrated implementation outcomes of acceptability, adoption, appropriateness, feasibility, implementation cost, penetration, and sustainability of MF‐PEP at these clinics. Parents also demonstrated significant improvement in knowledge of mood disorders posttreatment. Preliminary results support implementation of MF‐PEP in practice settings and suggest community‐based MF‐PEP may be associated with improvement in clinical outcomes.

Genome‐wide association studies (GWAS) of complex traits have generated many association signals for single nucleotide polymorphisms (SNPs). To understand the underlying causal genetic variant(s), focused DNA resequencing of targeted genomic regions is commonly used, yet the current cost of resequencing limits sample sizes for resequencing studies. Information from the large GWAS can be used to guide choice of samples for resequencing, such as the SNP genotypes in the targeted genomic region. Viewing the GWAS tag‐SNPs as imperfect surrogates for the underlying causal variants, yet expecting that the tag‐SNPs are correlated with the causal variants, a reasonable approach is a two‐phase case‐control design, with the GWAS serving as the first‐phase and the resequencing study serving as the second‐phase. Using stratified sampling based on both tag‐SNP genotypes and case‐control status, we explore the gains in power of a two‐phase design relative to randomly sampling cases and controls for resequencing (i.e., ignoring tag‐SNP genotypes). Simulation results show that stratified sampling based on both tag‐SNP genotypes and case‐control status is not likely to have lower power than stratified sampling based only on case‐control status, and can sometimes have substantially greater power. The gain in power depends on the amount of linkage disequilibrium between the tag‐SNP and causal variant alleles, as well as the effect size of the causal variant. Hence, the two‐phase design provides an efficient approach to follow‐up GWAS signals with DNA resequencing.

SummaryBackgroundCurrent approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD‐CRN) are suboptimal.AimTo test the feasibility of using stool assay of exfoliated DNA markers to detect IBD‐CRN.MethodsThis investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD‐CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD‐CRN and 35 age‐ and sex‐matched IBD controls without CRN. From stool‐extracted DNA, target genes were assayed using quantitative allele‐specific real‐time target and signal amplification method.ResultsIBD‐CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD‐CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade.ConclusionThese findings demonstrate the feasibility of stool DNA testing for non‐invasive detection of colorectal neoplasia associated with inflammatory bowel disease.

Disease overviewPrimary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell‐derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.DiagnosisDiagnosis is based on bone marrow morphology. The presence of fibrosis,JAK2/MPLmutation, or +9/13q− cytogenetic abnormality is supportive but not essential for diagnosis. PrefibroticPMFmimics essential thrombocythemia in its presentation and the distinction is prognostically relevant. Differential diagnosis of myelofibrosis should include chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.Risk stratificationThe Dynamic International Prognostic Scoring System‐plus (DIPSS‐plus) prognostic model forPMFcan be applied at any point during the disease course and uses eight independent predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 × 109/L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 × 109/L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, −7/7q−, i(17q), inv(3), −5/5q−, 12p−, or 11q23 rearrangement). The presence of 0, 1, “2 or 3,” and ≥4 adverse factors defines low, intermediate‐1, intermediate‐2, and high‐risk disease with median survivals of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. A >80% two‐year mortality is predicted by monosomal karyotype, inv(3)/i(17q) abnormalities, or any two of circulating blasts >9%, leukocytes ≥40 × 109/L or other unfavorable karyotype. Most recently, mutations involvingASXL1,SRSF2,EZH2, andIDH1/2or increased plasma IL‐2R, IL‐8, or serum‐free light chain levels have been shown to adversely affect survival.Risk‐adapted therapyObservation alone is adequate for asymptomatic low/intermediate‐1 risk disease. Allogeneic stem cell transplantation (ASCT) is often considered for high risk disease. Conventional or experimental drug therapy is reasonable for symptomatic intermediate‐1 or intermediate‐2 risk disease; however,ASCTis an acceptable treatment option for such patients in the presence ofASXL1or other prognostically adverse mutations. Splenectomy and low‐dose radiotherapy are used for drug‐refractory splenomegaly. Radiotherapy is also used for the treatment of non‐hepatosplenicEMH,PMF‐associated pulmonary hypertension, and extremity bone pain. Am. J. Hematol. 88:141–150, 2013. © 2012 Wiley Periodicals, Inc.

Background The platelet (PLT) P an G enera D etection test ( PGD ) is a rapid bacterial detection system used to screen PLTs for bacterial contamination. We report a single center 46‐month experience with secondary screening of apheresis PLTs by PGD testing. Study Design and Methods Existing testing records of apheresis PLTs screened by PGD from J uly 2008 to A pril 2012 were reviewed. All PLT units were initially screened by routine postcollection culture methods. Secondary screening using PGD was performed for indated PLTs on PLT storage D ay 4 and for outdated PLTs on D ay 8. Results A total of 8535 apheresis PLTs were available in inventory during the study period. Of these, 5030 (58.9%) were dispensed and transfused before PGD testing and 3505 (41.1%) underwent PGD testing on D ay 4. Twenty‐five units tested on D ay 4 were PGD initial reactive (0.71%). All were confirmed to be false positive by repeat PGD testing in triplicate (n = 20) or by confirmatory culture (n = 5). An additional 364 units that were PGD nonreactive on D ay 4 were approved for transfusion on D ay 6 or D ay 7 due to urgent clinical need. A total of 371 outdated units underwent repeat PGD testing before discard on D ay 8; all were nonreactive. Conclusion Secondary PGD testing of culture‐screened apheresis PLTs results in low yield in a medium‐sized transfusion service. Use of PGD testing on D ay 4 may allow for extension of the apheresis PLT shelf life to D ay 7 for hospitals that face supply constraints.

ABSTRACT We present a duplex, real-time PCR assay for detection of Klebsiella pneumoniae carbapenemase ( bla KPC ) and New Delhi metallo-β-lactamase ( bla NDM ) genes. Accuracy was assessed with 158 Gram-negative bacillary isolates, including 134 carbapenemase producers. The assay had 100% sensitivity and specificity compared with reference methods and a turnaround time of 90 min.

Background and objective Sacroplasty has emerged as a treatment option for patients with painful osteoporotic sacral insufficiency fractures. We report short-term outcomes in a consecutive cohort of patients treated with sacroplasty. Methods We retrospectively reviewed 57 patients treated with sacroplasty for painful osteoporotic sacral fractures at our institution between 2004 and 2011. An 11-point numerical rating scale pain score was recorded at rest and at activity pre- and post-procedure. Opioids prescribed to the patient both pre- and post-procedure were recorded. Results Mean duration of pain prior to sacroplasty was 3 weeks (IQR 2–5). Procedural complications were minimal. Median post-procedure follow-up time was 2.5 weeks (IQR 1–5) among 45 patients with available data. Thirty-seven (82%) of the 45 patients experienced a numerical or descriptive decrease from initial pain at follow-up. Median activity pain scores collected from 13 patients decreased from 10 (IQR 8.5–10) pre-procedure to 6 (IQR 4–6.8) post-procedure (p<0.0001), and median rest pain scores collected from 29 patients decreased from 7 (IQR 4–8.5) to 2 (IQR 1–3.5)(p<0.0001). Twenty-two (76%) of 29 patients had at least a 30% decrease in rest pain scores. The median number of opioids prescribed per patient decreased from 1 (IQR 1–2) pre-procedure to 0 (IQR 0–1) post-procedure (p<0.0001). Thirty-four of 57 patients (60%) had decreased opioid usage, 15 (26%) patients had unchanged usage and 8 (14%) had increased usage. Conclusions Our series demonstrates that sacroplasty is a safe and effective treatment in patients with painful osteoporotic insufficiency fractures.