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.     

Shwachman syndrome: Exocrine pancreatic dysfunction and variable phenotypic expression

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602)     

Incidence of nonsustained and sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator

INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) is a frequent phenomenon in some patients with heart disease, but its association with sustained ventricular tachycardias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) is still not clear. The aim of this study was to determine whether NSVT incidence was associated with sustained VT/VF in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Retrospective data analysis was conducted in 923 ICD patients with a mean follow-up of 4 months. NSVT and sustained VT/VF were defined as device-detected tachycardias. The incidence rates of NSVT and sustained VT/VF as well as ICD therapies were determined as episodes per patient. The NSVT index was defined as the product of NSVT episodes/day times the mean number of beats per episode, i.e., total beats/day. The NSVT index peak was defined as the highest value on or prior to the day with sustained VT/VF episodes. Patients (n = 393) with NSVT experienced a higher incidence of sustained VT/VF (17.2 +/- 63.0 episodes/patient) and ICD therapies (15.2 +/- 61.4 episodes/patient) than patients (n = 530) without NSVT (sustained VT/VF: 0.5 +/- 6.6 and therapies: 0.5 +/- 5.6; P < 0.0001). Approximately 74% of NSVT index peaks occurred on the same day or <3 days prior to sustained VT/VF episodes. The index was higher for peaks < or =3 days prior to the day with sustained VT/VF (94.3 +/- 140.1 total beats/day) than for peaks >3 days prior to the day with sustained VT/VF (32.7 +/- 55.9 total beats/day; P < 0.0001). CONCLUSION: ICD patients with NSVT represent a population more likely to experience sustained VT/VF episodes with a temporal association between an NSVT surge and sustained VT/VF occurrence.     

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.