Study objective Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized ...trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy. Methods Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate. Results Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/μL (range 6,200 to 23,100/μL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval CI 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group. Conclusion A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary Background Raltegravir (MK-0518) is an HIV-1 integrase inhibitor with potent in-vitro activity against HIV-1 strains including those resistant to currently available antiretroviral drugs. The ...aim of this study was to assess the safety and efficacy of raltegravir when added to optimised background regimens in HIV-infected patients. Methods HIV-infected patients with HIV-1 RNA viral load over 5000 copies per mL, CD4 cell counts over 50 cells per μL, and documented genotypic and phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, and one protease inhibitor were randomly assigned to receive raltegravir (200 mg, 400 mg, or 600 mg) or placebo orally twice daily in this multicentre, triple-blind, dose-ranging, randomised study. The primary endpoints were change in viral load from baseline at week 24 and safety. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov , with the number NCT00105157. Findings 179 patients were eligible for randomisation. 44 patients were randomly assigned to receive 200 mg raltegravir, 45 to receive 400 mg raltegravir, and 45 to receive 600 mg raltegravir; 45 patients were randomly assigned to receive placebo. One patient in the 200 mg group did not receive treatment and was therefore excluded from the analyses. For all groups, the median duration of previous antiretroviral therapy was 9·9 years (range 0·4–17·3 years) and the mean baseline viral load was 4·7 (SD 0·5) log10 copies per mL. Four patients discontinued due to adverse experiences, three (2%) of the 133 patients across all raltegravir groups and one (2%) of the 45 patients on placebo. 41 patients discontinued due to lack of efficacy: 14 (11%) of the 133 patients across all raltegravir groups and 27 (60%) of the 45 patients on placebo. At week 24, mean change in viral load from baseline was −1·80 (95% CI −2·10 to −1·50) log10 copies per mL in the 200 mg group, −1·87 (−2·16 to −1·58) log10 copies per mL in the 400 mg group, −1·84 (−2·10 to −1·58) log10 copies per mL in the 600 mg group, and −0·35 (−0·61 to −0·09) log10 copies per mL for the placebo group. Raltegravir at all doses showed a safety profile much the same as placebo; there were no dose-related toxicities. Interpretation In patients with few remaining treatment options, raltegravir at all doses studied provided better viral suppression than placebo when added to an optimised background regimen. The safety profile of raltegravir is comparable with that of placebo at all doses studied.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Radiofrequency catheter ablation is used to treat recurrent ventricular tachycardia (VT). Objectives This study evaluated long-term safety and effectiveness of radiofrequency ...catheter ablation using an open-irrigated catheter. Methods Patients with sustained monomorphic ventricular tachycardia associated with coronary disease were analyzed for cardiovascular-specific adverse events within 7 days of treatment, hospitalization duration, 6-month sustained monomorphic ventricular tachycardia recurrence, quality of life measured by the Hospital Anxiety and Depression Scale, long-term (1-, 2-, and 3-year) survival, symptomatic VT control, and amiodarone use. Results Overall, 249 patients, mean age 67.4 years, were enrolled. The cardiovascular-specific adverse events rate was 3.9% (9 of 233) with no strokes. Noninducibility of targeted VT was achieved in 75.9% of patients. Post-ablation median hospitalization was 2 days. At 6 months, 62.0% (114 of 184) of patients had no sustained monomorphic ventricular tachycardia recurrence; the proportion of patients with implantable cardioverter-defibrillator shocks decreased from 81.2% to 26.8% (p < 0.0001); the frequency of VT in implantable cardioverter-defibrillator patients with recurrences was reduced by ≥50% in 63.8% of patients; and the proportion with normal Hospital Anxiety and Depression Scale scores increased from 48.8% to 69.1% (p < 0.001). Patient-reported VT remained steady for 1, 2, and 3 years at 22.7%, 29.8%, and 24.1%, respectively. Amiodarone use and hospitalization decreased from 55% and 77.2% pre-ablation to 23.3% and 30.7%, 18.5% and 36.7%, 17.7% and 31.3% at 1, 2, and 3 years, respectively. Conclusions Radiofrequency catheter ablation reduced implantable cardioverter-defibrillator shocks and VT episodes and improved quality of life at 6 months. A steady 3-year nonrecurrence rate with reduced amiodarone use and hospitalizations indicate improved long-term outcomes. (NaviStar ThermoCool Catheter for Endocardial RF Ablation in Patients With Ventricular Tachycardia THERMOCOOL VT; NCT00412607 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Several types of forceps are available for use in sampling Barrett's esophagus (BE). Few data exist with regard to biopsy quality for histologic assessment. Objective To evaluate sampling ...quality of 3 different forceps in patients with BE. Design Single-center, randomized clinical trial. Patients Consecutive patients with BE undergoing upper endoscopy. Interventions Patients randomized to have biopsy specimens taken with 1 of 3 types of forceps: standard, large capacity, or jumbo. Main Outcome Measurements Specimen adequacy was defined a priori as a well-oriented biopsy sample 2 mm or greater in diameter and with at least muscularis mucosa present. Results A total of 65 patients were enrolled and analyzed (standard forceps, n = 21; large-capacity forceps, n = 21; jumbo forceps, n = 23). Compared with jumbo forceps, a significantly higher proportion of biopsy samples with large-capacity forceps were adequate (37.8% vs 25.2%, P = .002). Of the standard forceps biopsy samples, 31.9% were adequate, which was not significantly different from specimens taken with large-capacity ( P = .20) or jumbo ( P = .09) forceps. Biopsy specimens taken with jumbo forceps had the largest diameter (median, 3.0 mm vs 2.5 mm standard vs 2.8 mm large capacity; P = .0001). However, jumbo forceps had the lowest proportion of specimens that were well oriented (overall P = .001). Limitations Heterogeneous patient population precluded dysplasia detection analyses. Conclusions Our results challenge the requirement of jumbo forceps and therapeutic endoscopes to properly perform the Seattle protocol. We found that standard and large-capacity forceps used with standard upper endoscopes produced biopsy samples at least as adequate as those obtained with jumbo forceps and therapeutic endoscopes in patients with BE.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Telephone Intervention to Improve Diabetes Control Chamany, Shadi, MD, MPH; Walker, Elizabeth A., PhD, RN; Schechter, Clyde B., MA, MD ...
American journal of preventive medicine,
December 2015, Volume:
49, Issue:
6
Journal Article
Peer reviewed
Open access
Introduction Scalable self-management interventions are necessary to address suboptimal diabetes control, especially among minority populations. The study tested the effectiveness of a telephone ...behavioral intervention in improving glycemic control among adults with diabetes in the New York City A1c Registry. Design RCT comparing a telephone intervention to print-only intervention in the context of the A1c Registry program. Setting/participants Nine hundred forty-one adults with diabetes and hemoglobin A1c (A1c) >7% from a low-income, predominantly Latino population in the South Bronx were recruited from the A1c Registry. Intervention All study participants were mailed print diabetes self-management materials at baseline and modest lifestyle incentives quarterly. Only the telephone participants received four calls from health educators evenly spaced over 1 year if baseline A1c was >7%–9%, or eight calls if baseline A1c was >9%. Medication adherence was the main behavioral focus and, secondarily, nutrition and exercise. Main outcome measures Primary outcome was difference between two study arms in change in A1c from baseline to 1 year. Secondary outcomes included diabetes self-care activities, including self-reported medication adherence. Data were collected in 2008–2012 and analyzed in 2012–2014. Results Participants were predominantly Latino (67.7%) or non-Latino black (28%), with 69.7% foreign-born and 55.1% Spanish-speaking. Among 694 (74%) participants with follow-up A1c, mean A1c decreased by 0.9 (SD=0.1) among the telephone group compared with 0.5 (SD=0.1) among the print-only group, a difference of 0.4 (95% CI=0.09, 0.74, p =0.01). The intervention had significant effect when baseline A1c was >9%. Both groups experienced similar improvements in self-care activities, medication adherence, and intensification. Conclusions A telephone intervention delivered by health educators can be a clinically effective tool to improve diabetes control in diverse populations, specifically for those with worse metabolic control identified using a registry. This public health approach could be adopted by health systems supported by electronic record capabilities. ClinicalTrials.gov Registration NCT00797888.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In February 2019, following the annual taxon ratification vote, the order
Bunyavirales
was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of ...two species, and deletion of one species. This article presents the updated taxonomy of the order
Bunyavirales
now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense ...variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three‐nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain.
We report a Malian and Brazilian families affected with hereditary spastic paraplegia (SPG43) and “forme frustre” neurodegeneration with brain iron accumulation (NBIA), respectively. The same mutation (C19orf12, p.Ala63Pro) and haplotype were found in these families, but MRI scans showed no brain iron deposition in the Malian subjects. Heterologous expression of this SPG43 and NBIA variant resulted in alteration in the subcellular distribution of C19orf12. Further studies are needed to unravel other genetic or environmental factors underlining these phenotypic differences.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives This report calls attention to an unappreciated cause of both acute and chronic aortic regurgitation (AR). Background Although stenosis develops in most patients with a congenitally ...bicuspid aortic valve (BAV), in others with this anomaly, pure AR (no element of stenosis) develops, some in the absence of infection or other clear etiology. Methods We describe 5 men who underwent aortic valve replacement for pure AR associated with a BAV containing an anomalous cord attaching the raphe of the conjoined cusp near its free margin to the wall of the ascending aorta cephalad to the sinotubular junction. Results Three of these 5 patients had a history of progressive dyspnea, and the anomalous cord, which was intact at operation, appeared to cause chronic AR by preventing proper coaptation of the 2 aortic valve cusps. The other 2 patients heard a “pop” during physical exertion and immediately became dyspneic, and at operation, the anomalous cord was found to have ruptured. Prolapse of the conjoined aortic valve cusp toward the left ventricular cavity resulted in severe acute AR. Conclusions This variant of the purely regurgitant BAV may cause either chronic AR (when the anomalous cord does not rupture) or acute severe AR (when the cord ruptures).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global ...Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. Methods We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. Findings Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. Interpretation Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. Funding Bill & Melinda Gates Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Chemoradiation, followed by adjuvant temozolomide, is the standard treatment for newly diagnosed glioblastoma. Adding other active agents may enhance treatment efficacy.
The primary objective of this ...factorial phase II study was to determine if one of 3 potential chemotherapy agents added to dose-dense temozolomide (ddTMZ) improves progression-free survival (PFS) for patients with newly diagnosed glioblastoma. A prior phase I trial established the safety of combining ddTMZ with isotretinoin, celecoxib, and/or thalidomide. Adults with good performance status and no evidence of progression post chemoradiation were randomized into 8 arms: ddTMZ alone (7 days on/7 days off) or doublet, triplet, and quadruplet combinations with isotretinoin, celecoxib, and thalidomide.
The study enrolled 155 participants with a median age of 53 years (range, 18-84 y). None of the agents demonstrated improved PFS when compared with arms not containing that specific agent. There was no difference in PFS for triplet compared with doublet regimens, although a trend for improved overall survival (OS) was seen (20.1 vs 17.0 months, P = .15). Compared with ddTMZ, the ddTMZ + isotretinoin doublet had worse PFS (10.5 vs 6.5 months, P = .043) and OS (21.2 vs 11.7 months, P = .037). Trends were also seen for worse outcomes with isotretinoin-containing regimens, but there was no impact with celecoxib or thalidomide combinations. Treatment was well tolerated with expected high rates of lymphopenia.
The results do not establish a benefit for these combinations but indicate that adding isotretinoin to ddTMZ may be detrimental. This study demonstrated the feasibility and utility of the factorial design in efficiently testing drug combinations in newly diagnosed glioblastoma.
NCT00112502.
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