Delayed esophageal perforation after pneumatic dilatation for the treatment of achalasia

Two cases of delayed esophageal perforation following a pneumatic dilatation for the treatment of achalasia are presented. Esophagrams obtained immediately after pneumatic dilatation failed to reveal a perforation. Increasing symptoms prompted repeat contrast studies, at which time an esophageal perforation was demonstrated. The occurrence of delayed esophageal perforation after pneumatic instrumentation is emphasized. An ischemic etiology for this delayed perforation is postulated.     

4H-1,4-benzothiazine, dihydro-1,4-benzothiazinones and 2-amino-5-fluorobenzenethiol derivatives: design, synthesis and in vitro antimicrobial screening

As part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7‐fluoro‐3,4‐dihydro‐2H‐1,4‐benzothiazine derivatives ( 4a–4f , 4h ) and 7‐fluoro‐2H‐1,4‐benzothiazin‐3(4H)‐one analogues ( 4j–4o ) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram‐positive and Gram‐negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro‐substituted‐2‐amino‐5‐fluorobenzenethiol 6a–6c . The biological screening identified in compounds 4a , 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermediates 6a–6c . Surprisingly, 6a–6c emerged as the compounds exhibiting the highest antimicrobial activity by possessing a remarkable antibacterial effect against the Gram‐positive strains with MIC (minimal inhibitory concentration) values between 2 and 8 µg/mL and the fungi panel with MIC values between 2 and 8 µg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents.     

Evidence-based policy-making: The implications of globally-applicable research for context-specific problem-solving in developing countries

In the past 15 or so years, the “evidence-based medicine” (EBM) framework has become increasingly institutionalized, facilitating its transfer across the globe. In the late 1990s, the basic principles of EBM began to have a marked influence in a number of non-clinical public policy arenas. Policy-makers working in these areas are now being urged to move away from developing policies according to political ideologies to a more legitimate approach based on “scientific fact,” a process termed “evidence-based policy-making” (EBPM). The conceptual diffusion of EBM to non-clinical arenas has exposed epistemologically destabilizing views regarding the definition of “science,” particularly as it relates to the demands of global versus national/sub-national policy-making. Using the maternal and neonatal subfield as an ethnographic case-study, this paper explores the effects of these divergences on EBPM in 5 developing countries (Bangladesh, Burkina Faso, Ghana, Malawi and Nepal). In doing so, our analysis aims to explain why EBPM has thus far had a limited impact in the area of context-specific programmatic policy-development and implementation at the national and sub-national levels. Results highlight that the political contexts in which EBPM is played out promote uniformity of methodological and policy approaches, despite the fact that disciplinary diversity is being called for repeatedly in the public health literature. Even in situations where national EBPM diverges from international priorities, national evidence-based policies are found to hold little weight in countering global policy interests, which some informants claim are themselves legitimated, rather than informed, by evidence. Informants also highlight the way interpretations of research findings are shaped by the broader political context within which donors set priorities and distribute limited resources – contexts that are driven by the need to provide generalisable research recommendations based on scientifically replicable methods. Added to this are clear rifts between senior and junior-level experts within countries that constrain national and sub-national research agendas from serving as tools for empowered knowledge production and problem-solving. We conclude by arguing for diverse forms of research that can more effectively address context-specific problems. While such diversity may render EBPM more conflict-ridden, debate is by no means an undesirable characteristic in any evolving system of knowledge, for it has the potential to foster critical insight and localized change.     

Biopsy findings after breast conservation therapy for early-stage invasive breast cancer

PURPOSE: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.     

Evaluating effectiveness of preoperative testing procedure: some notes on modelling strategies in multi-centre surveys

Rationale In technology assessment in health‐related fields the construction of a model for interpreting the economic implications of the introduction of a technology is only a part of the problem. The most important part is often the formulation of a model that can be used for selecting patients to submit to the new cost‐saving procedure or medical strategy. The model is usually complicated by the fact that data are often non‐homogeneous with respect to some uncontrolled variables and are correlated. The most typical example is the so‐called hospital effect in multi‐centre studies. Aims and objectives We show the implications derived by different choices in modelling strategies when evaluating the usefulness of preoperative chest radiography, an exam performed before surgery, usually with the aim to detect unsuspected abnormalities that could influence the anaesthetic management and/or surgical plan. Method We analyze the data from a multi‐centre study including more than 7000 patients. We use about 6000 patients to fit regression models using both a population averaged and a subject‐specific approach. We explore the limitations of these models when used for predictive purposes using a validation set of more than 1000 patients. Results We show the importance of taking into account the heterogeneity among observations and the correlation structure of the data and propose an approach for integrating a population‐averaged and subject specific approach into a single modeling strategy. We find that the hospital represents an important variable causing heterogeneity that influences the probability of a useful POCR. Conclusions We find that starting with a marginal model, evaluating the shrinkage effect and eventually move to a more detailed model for the heterogeneity is preferable. This kind of flexible approach seems to be more informative at various phases of the model‐building strategy.     

Unilateral phrenic nerve paralysis: a rare complication after total thyroidectomy for a large cervico-mediastinal goitre

Unilateral phrenic nerve paralysis is a rare complication of cervico-mediastinal goitre. It occurs when adhesions grow between the intrathoracic part of the thyroid and the nerve, specially where the goitre enters the mediastinum behind the first rib. The damage may be caused by strain of the nerve due to the descent of the goitre into the chest or may be caused by the surgical manoeuvres during thyroidectomy performed by cervical approach. Two patients operated on for large cervico-mediastinal goitre are reported: a 70-year-old male with a large intrathoracic growth of the left thyroid lobe and a 54-year-old male with a large intrathoracic growth to the right lobe. A few days after total thyroidectomy they showed signs of exertional dyspnoea. The exams performed showed hemi-diaphragm relaxatio due to phrenic nerve paralysis, with resulting reduction of respiratory space. Phrenic nerve paralysis may follow total thyroidectomy for large cervico-mediastinal goitres; is not due to the operative technique, but rather to the particular anatomic conditions which may be found.