Project description:SLC6A4, the gene encoding the serotonin transporter protein (5-HTT), has been extensively examined as a risk factor for alcohol dependence (AD). More recently, variability in the transporter gene was identified to be a potential moderator of treatment response to serotonergic medications such as ondansetron and sertraline. There is an insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the SLC6A4, with the most common alleles being a 14-repeat short (S) allele and a 16-repeat long (L) allele. The S allele has often been associated with AD. By contrast, the L allele has been associated with pharmacological responsiveness in some individuals with AD. Differences in clinical phenotype may determine the utility of the 5-HTTLPR polymorphism as a moderator of pharmacological interventions for AD. We review the AD typology and disease onset in the context of pharmacogenetic and genomic studies that examine the utility of 5-HTTLPR in improving treatment outcomes.
Project description:BackgroundProject MATCH was the largest and most expensive alcoholism treatment trial ever conducted. The results were disappointing. There were essentially no patient-treatment matches, and three very different treatments produced nearly identical outcomes. These results were interpreted post hoc as evidence that all three treatments were quite effective. We re-analyzed the data in order to estimate effectiveness in relation to quantity of treatment.MethodsThis was a secondary analysis of data from a multisite clinical trial of alcohol dependent volunteers (N = 1726) who received outpatient psychosocial therapy. Analyses were confined to the primary outcome variables, percent days abstinent (PDA) and drinks per drinking day (DDD). Overall tests between treatment outcome and treatment quantity were conducted. Next, three specific groups were highlighted. One group consisted of those who dropped out immediately; the second were those who dropped out after receiving only one therapy session, and the third were those who attended 12 therapy sessions.ResultsOverall, a median of only 3% of the drinking outcome at follow-up could be attributed to treatment. However this effect appeared to be present at week one before most of the treatment had been delivered. The zero treatment dropout group showed great improvement, achieving a mean of 72 percent days abstinent at follow-up. Effect size estimates showed that two-thirds to three-fourths of the improvement in the full treatment group was duplicated in the zero treatment group. Outcomes for the one session treatment group were worse than for the zero treatment group, suggesting a patient self selection effect. Nearly all the improvement in all groups had occurred by week one. The full treatment group had improved in PDA by 62% at week one, and the additional 11 therapy sessions added only another 4% improvement.ConclusionThe results suggest that current psychosocial treatments for alcoholism are not particularly effective. Untreated alcoholics in clinical trials show significant improvement. Most of the improvement which is interpreted as treatment effect is not due to treatment. Part of the remainder appears to be due to selection effects.
Project description:ObjectiveObesity is a major public health challenge, and the US military veteran population is disproportionately affected. Using deidentified records from a local weight management clinic and a national clinical data repository, obesity pharmacotherapy use and effectiveness for weight loss and obesity comorbidities in this vulnerable population were assessed.MethodsDuring the initial year of the local clinic, 43 records with monthly follow-up of MOVE! lifestyle intervention augmented by obesity pharmacotherapy were found. Nationally, more than 2 million records of prescribed obesity pharmacotherapy compared with metformin as control were identified. Records with detailed documentation of weight trends from 1 year before to 1 year after the prescription date for further analysis were selected for review.ResultsThe most commonly prescribed medications in the local clinic were metformin, liraglutide, and combination phentermine/topiramate. On average, weight loss of -4.0 ± 2.1 kg over the initial 6-month intervention was observed. In the national cohort, 577,491 records with an obesity or control metformin prescription and adequate weight documentation were identified. The most effective pharmacotherapy in the national cohort was phentermine/topiramate (-0.0931 ± 0.0198 kg/wk difference), followed by liraglutide, lorcaserin, and orlistat.ConclusionsObesity pharmacotherapy is effective in achieving clinically meaningful weight loss in veterans as part of an integrated care approach.
Project description:Application of ultrasound to evaluate pediatric respiratory disease in the emergency department setting is rapidly growing, particularly as we often weigh the risks of exposure to radiation with other readily available imaging modalities in the acute care setting. In this case report, we describe how point of care ultrasound (POCUS) was utilized by emergency providers to characterize a lung abscess diagnosed in a pediatric patient. We also compare the ultrasound findings to other imaging studies.
Project description:Nocardia cerebral abscess is rare, constituting approximately 1-2% of all cerebral abscesses. Mortality for a cerebral abscess of Nocardia is three times higher than that of other bacterial cerebral abscesses, therefore, early diagnosis and therapy is important. Nocardia cerebral abscess is generally occur among immunocompromised patients, and critical infection in immunocompetent patients is extremely rare. We report on a case of a brain abscess by Nocardia farcinica in an immunocompetent patient who received treatment with surgery and antibiotics. This is the second case of a brain abscess caused by N. farcinica in an immunocompetent patient in Korea.
Project description:Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. HS mimicking compounds that inhibit heparanase enzymatic activity were examined in numerous preclinical cancer models. While these studies utilized established tumor cell lines, the current study utilized, for the first time, patient-derived xenografts (PDX) which better resemble the behavior and drug responsiveness of a given cancer patient. We have previously shown that heparanase levels are substantially elevated in lung cancer, correlating with reduced patients survival. Applying patient-derived lung cancer xenografts and a potent inhibitor of heparanase enzymatic activity (PG545) we investigated the significance of heparanase in the pathogenesis of lung cancer. PG545 was highly effective in lung cancer PDX, inhibiting tumor growth in >85% of the cases. Importantly, we show that PG545 was highly effective in PDX that did not respond to conventional chemotherapy (cisplatin) and vice versa. Moreover, we show that spontaneous metastasis to lymph nodes is markedly inhibited by PG545 but not by cisplatin. These results reflect the variability among patients and strongly imply that PG545 can be applied for lung cancer therapy in a personalized manner where conventional chemotherapy fails, thus highlighting the potential benefits of developing anti-heparanase treatment modalities for oncology.
Project description:We describe a previously healthy patient with chronic otitis media complicated with cerebellar abscess caused by Tsukamurella tyrosinosolvens. The organism was identified based on conventional biochemical identification methods, PCR-restriction fragment length polymorphism analysis of the hsp65 gene, and 16S rRNA gene sequencing. The patient was treated successfully with debridements and prolonged antibiotic therapy.
Project description:Phaeoacremonium parasiticum is an environmental fungus usually associated with subcutaneous infections. We report the first documented case of central nervous system involvement with brain abscess formation in a patient with chronic granulomatous disease and review the literature on Phaeoacremonium parasiticum infections.
Project description:Background. Prostatic abscess is rare and mainly affects immunocompromised individuals, classically presenting with both systemic and lower urinary tract symptoms. Our case is unique as the patient presented with an exceptionally long duration of symptoms prior to seeing a health-care provider, had no systemic symptoms, and was managed via a multidisciplinary approach. Case Presentation. We present a case of a 70-year-old man with type-two diabetes who endured two months of lower urinary tract symptoms and constipation without systemic symptoms prior to seeking medical attention. He had a positive urinalysis and culture and was initially thought to have a urinary tract infection; however, computed tomography scan revealed a large, complex, and multiloculated prostatic abscess. Multidisciplinary drainage of the abscess was performed by interventional radiology and urology. A postoperative Foley catheter was left in place, and the patient recovered without complications. Discussion. Prostatic abscess is uncommon and presents almost exclusively in patients with immunocompromising conditions such as diabetes. Prior to the advent of antibiotics, the major causes were gonorrheal and Staphylococcus aureus infections, but with the advent of antibiotics, microbial culprits have shifted to gram-negative organisms. Patients typically present with lower urinary tract symptoms, perineal or lower back pain, and systemic symptoms. Management often consists of intravenous antibiotics and surgical drainage either by transrectal ultrasound-guided needle aspiration, or transurethral deroofing of the prostate. Our case highlights the following: (a) the importance of a high index of suspicion for a prostatic abscess in an immunocompromised patient with persistent leukocytosis and perineal pain after treatment with antibiotics and (b) the potential for an early multidisciplinary approach to draining extensive, loculated prostatic abscesses.