Clinical profile,management and outcome of pulmonary embolism in Shahid Gangalal National Heart Centre,Kathmandu, Nepal

Background and aims

Pulmonary embolism (PE) is associated with a significant mortality and morbidity. We aim to study clinical profile, management and outcome of PE at Shahid Gangalal National heart Centre, Kathmandu, Nepal.

The role of APACHE-II triaging in optimum management of small bowel perforations.

Small bowel perforations with peritonitis pose a serious problem to an emergency surgeon because of the lack of any uniformity of opinion regarding the optimum surgical treatment to be performed. This may be attributed to lack of any common and reliable scoring system. A prospective study to discover the utility of APACHE-II triaging in small bowel perforations was conducted over a period of 14 months on 51 patients with small bowel perforations of various aetiologies. The triaging facilitated definitive surgical treatments based on the predictive value of APACHE-II scoring. The classification of patients into three groups, effectively brought uniformity in the management. A significant reduction in mortality and cost-effective utilization of scarce intensive care unit resources were the dominant outcomes of this study conducted at a busy tertiary centre.     

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.     

Non-pharmacological management of phantom limb pain in lower limb amputation: a systematic review

Background: The incidence and severity of phantom limb pain (PLP) does not differ much between the extremities of amputation. However, its impact on functional ability and quality of life in lower limb amputation may be different, as prosthetic weight bearing is a key component in the movement and functional rehabilitation of individuals with a lower limb amputation.

Objective: To evaluate the evidence for effectiveness or efficacy of non-pharmacological interventions in the management of PLP in adults with lower limb amputation.

Methods: A comprehensive literature search conducted on 11 electronic databases, from their inception to 25 March 2016 identified 626 potentially relevant articles. Full-text randomised controlled trials in English which examined any form of non-pharmacologic intervention for managing PLP in lower limb amputees were included. The data with regard to characteristics of the studies, participants, intervention and outcome measures and overall statistical result were extracted. The Cochrane ‘Risk of bias assessment tool’ was used to assess the bias of all included articles.

Results: Four studies met the final criteria to be included in the review. Four treatment techniques had been used in the treatment of 204 patients with lower limb amputation. Two trials showed a positive impact of intervention on PLP compared to control group. Risk of bias varied across studies, and only one included study was assessed as having a low risk of bias.

Conclusion: The review identified lack of evidence to support non-pharmacological interventions in the management of PLP. Adequately powered high-quality trials are needed in this area to inform rehabilitation.     

Bayesian probability of success for clinical trials using historical data

Developing sophisticated statistical methods for go/no‐go decisions is crucial for clinical trials, as planning phase III or phase IV trials is costly and time consuming. In this paper, we develop a novel Bayesian methodology for determining the probability of success of a treatment regimen on the basis of the current data of a given trial. We introduce a new criterion for calculating the probability of success that allows for inclusion of covariates as well as allowing for historical data based on the treatment regimen, and patient characteristics. A new class of prior distributions and covariate distributions is developed to achieve this goal. The methodology is quite general and can be used with univariate or multivariate continuous or discrete data, and it generalizes Chuang‐Stein's work. This methodology will be invaluable for informing the scientist on the likelihood of success of the compound, while including the information of covariates for patient characteristics in the trial population for planning future pre‐market or post‐market trials. Copyright © 2014 John Wiley & Sons, Ltd.     

Thyroid peroxidase autoantibodies obtained from random single chain FV libraries contain the same heavy/light chain combinations as occur in vivo

Three combinatorial libraries were constructed from unpurified, CD19(+), and antithyroid peroxidase (anti-TPO) B cells extracted from thyroid tissue of Graves' disease patients. Fifteen of the 41 randomly derived anti-TPO single chain variable region fragments (scFvs), showed VH1-3/V lambda 1-51 or VH1-69/V lambda 1-40 heavy/light chain pairing similar to that obtained with TPO-specific scFv derived from an in-cell library. One VH1-3/V lambda 1-51 scFv, A16, showed exactly the same nucleotide sequence as in-cell scFv ICB7, demonstrating that in vivo rearrangement can be obtained from a random combinatorial library. The majority of the scFvs used a heavy chain gene derived from the VH1-3 gene segment, whereas the light chain gene segments used were more heterogeneous, with dominance of the V kappa 1-39 and V lambda 1-51 gene segments. The anti-TPO scFvs showed high affinities to TPO, with values between 0.77 and 12.3 nM, and defined seven antigenic regions on the TPO molecule. The anti-TPO fragments, particularly VH1-3/V lambda 1-51 randomly associated scFv B4, which mimic natural H/L pairing, and VH1-3/V lambda 1-40 in-cell-derived scFv ICA5, efficiently displaced the TPO binding of serum autoantibodies from 20 Graves' disease patients. Our study directly demonstrates that antibodies derived from combinatorial libraries are likely to represent in vivo pairing, leading to high affinity antibody fragments mimicking the binding of serum autoantibodies to TPO.     

Imaging technologies and techniques

Equipment manufacturers provide contrast-specific detection techniques that have excellent sensitivity and excellent agent-to-tissue specificity along with helpful tools that improve workflow efficiency dramatically. Excellent contrast agents have been approved for LV opacification and are available worldwide. Techniques designed for low-MI imaging offer real-time acquisition capabilities and lead to faster examinations. Techniques designed for medium-MI imaging offer better sensitivity than low-MI techniques while maintaining the benefit of rapid image acquisition. Techniques designed for high-MI imaging offer the best sensitivity with longer acquisition times. These techniques are viable means for imaging contrast agents tailored to clinical needs. Progress by contrast agent manufacturers, equipment manufacturers, and physicians will continue to drive improvements in the areas of detection and clinical workflow for improved patient care.     

Typhoid fever caused by a typical variants of Salmonella typhi--a preliminary report

In the study carried out from, February, 1996 to January, 1999. 42 (33.9%) a typical variants of S typhi which fermented sucrose were encountered. This variant was identified as of antigenic structure 9, 12, v1, d1 and typed as phage type E1 and Bio type I.     

Time course of recovery showing initial prefrontal cortex changes at 16 weeks,extending to subcortical changes by 3 years in pediatric bipolar disorder

Objective

Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD).

Methods

Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge.

Results

At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum.

Limitations

Small sample size renders the present findings preliminary.

Conclusions

Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.