Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up

<p>Abstract</p> <p>Background</p> <p>Multi-drug resistant tuberculosis has emerged as a significant problem with the resurfacing of tuberculosis and thus the need to use the second line drugs with the resultant increased incidence of adverse effects. We discuss the effect of second line aminoglycoside anti-tubercular drugs on the hearing status of MDR-TB patients.</p> <p>Methods</p> <p>Sixty four patients were put on second line aminoglycoside anti-TB drugs. These were divided into three groups: group I, 34 patients using amikacin, group II, 26 patients using kanamycin and group III, 4 patients using capreomycin.</p> <p>Results</p> <p>Of these, 18.75% of the patients developed sensorineural hearing loss involving higher frequencies while 6.25% had involvement of speech frequencies also. All patients were seen again approximately one year after aminoglycoside discontinuation and all hearing losses were permanent with no threshold improvement.</p> <p>Conclusion</p> <p>Aminoglycosides used in MDR-TB patients may result in irreversible hearing loss involving higher frequencies and can become a hearing handicap as speech frequencies are also involved in some of the patients thus underlining the need for regular audiologic evaluation in patients of MDR-TB during the treatment.</p

Trends in Diagnosis and Surgical Management of Patients with Perforated Peptic Ulcer

Introduction While the laparoscopic treatment of perforated peptic ulcers (PPU) has been shown to be feasible and safe, its implementation into routine clinical practice has been slow. Only a few studies have evaluated its overall utility. The aim of this study was to investigate changes in surgical management of PPU and associated outcomes. Material and Methods The study was a retrospective, single institution, population-based review of all patients undergoing surgery for PPU between 2003 and 2009. Patient demographics, diagnostic evaluation, management, and outcomes were evaluated. Results Included were 114 patients with a median age of 67 years (range, 20–100). Women comprised 59% and were older (p<0.001), had more comorbidities (p=0.002), and had a higher Boey risk score (p=0.036) compared to men. Perforation location was gastric/pyloric in 72% and duodenal in 28% of patients. Pneumoperitoneum was diagnosed by plain abdominal x-ray in 30 of 41 patients (75%) and by abdominal computerized tomography (CT) in 76 of 77 patients (98%; p<0.001). Laparoscopic treatment was initiated in 48 patients (42%) and completed in 36 patients (75% of attempted cases). Laparoscopic treatment rate increased from 7% to 46% during the study period (p=0.02). Median operation time was shorter in patients treated via laparotomy (70 min) compared to laparoscopy (82 min) and those converted from laparoscopy to laparotomy (105 min; p=0.017). Postoperative complications occurred in 56 patients (49%). Overall 30-day postoperative mortality was 16%. No statistically significant differences were found in morbidity and mortality between open versus laparoscopic repair. Conclusion This study demonstrates an increased use of CT as the primary diagnostic tool for PPU and of laparoscopic repair in its surgical treatment. These changes in management are not associated with altered outcomes

Association of common ATM variants with familial breast cancer in a South American population

Background: The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. Methods: In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G > A missense variant and the IVS38-8T > C and the IVS24-9delT polymorphisms. Results: In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T > C, or 5557G > A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T > C (OR = 3.09 [95% CI 1.11-8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [ 95% CI 1.16-8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. Conclusion: The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response

Tolerability of breast ductal lavage in women from families at high genetic risk of breast cancer

<p>Abstract</p> <p>Background</p> <p>Ductal lavage (DL) has been proposed as a minimally-invasive, well-tolerated tool for obtaining breast epithelial cells for cytological evaluation of breast cancer risk. We report DL tolerability in <it>BRCA1/2 </it>mutation-positive and -negative women from an IRB-approved research study.</p> <p>Methods</p> <p>165 <it>BRCA1/2 </it>mutation-positive, 26 mutation-negative and 3 mutation unknown women underwent mammography, breast MRI and DL. Psychological well-being and perceptions of pain were obtained before and after DL, and compared with pain experienced during other screening procedures.</p> <p>Results</p> <p>The average <b><it>anticipated </it></b>and <b><it>experienced </it></b>discomfort rating for DL, 47 and 48 (0–100), were significantly higher (<it>p </it>< 0.01) than the <b><it>anticipated </it></b>and <b><it>experienced </it></b>discomfort of mammogram (38 and 34), MRI (36 and 25) or nipple aspiration (42 and 27). Women with greater pre-existing emotional distress experienced more DL-related discomfort than they anticipated. Women reporting DL-related pain as worse than expected were nearly three times more likely to refuse subsequent DL than those reporting it as the same or better than expected. Twenty-five percent of participants refused repeat DL at first annual follow-up.</p> <p>Conclusion</p> <p>DL was anticipated to be and experienced as <b>more </b>uncomfortable than other procedures used in breast cancer screening. Higher underlying psychological distress was associated with decreased DL tolerability.</p

Increased prevalence of testicular microlithiasis in men with familial testicular cancer and their relatives

Testicular germ cell tumours (TGCT) cluster in families, but responsible genes remain unidentified. The association between testicular microlithiasis (TM) and testicular carcinoma in situ (CIS) suggests that TM may be a TC risk factor. We report testicular ultrasound findings in men with familial TGCT (FTGCT) and their unaffected relatives. A total of 81 men (48 affected and 33 unaffected) from 31 families with ⩾2 TC cases underwent testicular ultrasound. Testicular microlithiasis was defined as either ‘classic' (⩾5 microliths) or ‘limited' (<5 microliths). Statistical analyses used Fisher's exact test and permutation testing. Testicular microlithiasis was more frequent in the contralateral testicles of men with a history of TGCT (affected men) than in unaffected men (48 vs 24%, P=0.04). The association appeared stronger for classic TM (21 vs 9%) than for limited TM (27 vs 15%). Testicular microlithiases were bilateral in six out of seven (87%) unaffected men. Among affected men, TM was not associated with histology, age at diagnosis or cancer treatment. Of the 31 families, 10 accounted for a majority (61%) of the TM cases identified (P=0.11). Testicular microlithiasis was more prevalent among FTGCT family members than described previously in the general population, and was more common among FTGCT cases vs unaffected blood relatives. Testicular microlithiasis appeared to cluster in certain families. These findings suggest both a familial predisposition to TM and an association between TM and FTGCT. If proven, this could be clinically important to men in FTGCT families, and may be useful in identifying specific genes involved in FTGCT

CNS Recruitment of CD8+ T Lymphocytes Specific for a Peripheral Virus Infection Triggers Neuropathogenesis during Polymicrobial Challenge

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack

The needs of foster children and how to satisfy them:A systematic review of the literature

Family foster care deeply influences the needs of children and how these are satisfied. To increase our knowledge of foster children’s needs and how these are conceptualized, this paper presents a systematic literature review. Sixty- four empirical articles from six databases were reviewed and categorized (inter-rater agreement K = .78) into four categories: medical, belongingness, psychological and self-actualization needs. The results give a complete overview of needs that are specific to foster children, and what can be implemented to satisfy these needs. This study shows psychological needs are studied more often compared to the other categories, which specially relates to much attention for mental health problems. Furthermore, most articles focus on how to satisfy the needs of foster children and provide no definition or concrete conceptualization of needs. Strikingly, many articles focus on children’s problems instead of their needs, and some even use these terms interchangeably. This review illustrates that future research should employ a proper conceptualization of needs, which could also initiate a shift in thinking about needs instead of problems

A predictive model for the early identification of patients at risk for a prolonged intensive care unit length of stay

<p>Abstract</p> <p>Background</p> <p>Patients with a prolonged intensive care unit (ICU) length of stay account for a disproportionate amount of resource use. Early identification of patients at risk for a prolonged length of stay can lead to quality enhancements that reduce ICU stay. This study developed and validated a model that identifies patients at risk for a prolonged ICU stay.</p> <p>Methods</p> <p>We performed a retrospective cohort study of 343,555 admissions to 83 ICUs in 31 U.S. hospitals from 2002-2007. We examined the distribution of ICU length of stay to identify a threshold where clinicians might be concerned about a prolonged stay; this resulted in choosing a 5-day cut-point. From patients remaining in the ICU on day 5 we developed a multivariable regression model that predicted remaining ICU stay. Predictor variables included information gathered at admission, day 1, and ICU day 5. Data from 12,640 admissions during 2002-2005 were used to develop the model, and the remaining 12,904 admissions to internally validate the model. Finally, we used data on 11,903 admissions during 2006-2007 to externally validate the model.</p> <p>Results</p> <p>The variables that had the greatest impact on remaining ICU length of stay were those measured on day 5, not at admission or during day 1. Mechanical ventilation, PaO₂: FiO₂ratio, other physiologic components, and sedation on day 5 accounted for 81.6% of the variation in predicted remaining ICU stay. In the external validation set observed ICU stay was 11.99 days and predicted total ICU stay (5 days + day 5 predicted remaining stay) was 11.62 days, a difference of 8.7 hours. For the same patients, the difference between mean observed and mean predicted ICU stay using the APACHE day 1 model was 149.3 hours. The new model's r²was 20.2% across individuals and 44.3% across units.</p> <p>Conclusions</p> <p>A model that uses patient data from ICU days 1 and 5 accurately predicts a prolonged ICU stay. These predictions are more accurate than those based on ICU day 1 data alone. The model can be used to benchmark ICU performance and to alert physicians to explore care alternatives aimed at reducing ICU stay.</p