Cold-related mortality due to cardiovascular diseases, respiratory diseases and cancer: a case-crossover study.

Public Health. 2013 Feb 21;

Authors: Gómez-Acebo I, Llorca J, Dierssen T

Abstract
OBJECTIVES: The aim of this study was to identify the relationship between low temperatures in winter and mortality due to cancer, cardiovascular diseases and respiratory diseases. STUDY DESIGN: Case-crossover study. METHODS: A case-crossover study was performed in Cantabria (northern Spain) in the years 2004-2005; 3948 deaths were included. Odds ratios were estimated using conditional logistic regression, stratified by age, sex, and delay of exposure to low temperatures. RESULTS: There was an inverse dose-response relationship between temperature and mortality in the three causes of death studied; this result was consistent across genders and age groups. The higher OR for cancer mortality was seen on the first day of exposure (OR = 4.91; 95% CI: 1.65-13.07 in the whole population), and it decreased when exposure over several days in a row was considered; people aged 75 years or more were especially susceptible to cold temperatures (OR = 17.9; 95% CI: 2.38-134.8). Cardiovascular (OR = 2.63; 95% CI: 1.88-3.67) and respiratory mortality (OR = 2.72; 95% CI: 1.46-5.08) showed a weaker effect. CONCLUSION: There is a striking association between the extreme cold temperatures and mortality from cancer, not previously reported, which is more remarkable in the elderly. These results could be explained by a harvesting effect in which the cold acts as a trigger of death in terminally ill patients at high risk of dying a few days or weeks later.

PMID: 23433803 [PubMed - as supplied by publisher]

Bronchoscopic evaluation of unexplained recurrent and persistent pneumonia in children.

J Paediatr Child Health. 2013 Feb 26;

Authors: Gokdemir Y, Cakir E, Kut A, Erdem E, Karadag B, Ersu R, Karakoc F

Abstract
BACKGROUND: Persistent or recurrent pneumonia in children can pose a significant challenge to paediatricians and respiratory physicians. AIM: The aim of this study is to determine the role of flexible bronchoscopy (FB) in evaluation of recurrent or persistent pneumonia that remain otherwise unexplained by non-invasive diagnostic tests in children. METHODS: Retrospective evaluation of patients who underwent FB with an indication of recurrent or persistent pneumonia from 1997 to 2011. RESULTS: Among 2600 FB procedures, 434 (17%) were performed with the indication of recurrent or persistent pneumonia. There were 237 (54%) boys. Median age at presentation was 84 months, and median duration of symptoms was 9 months. FB led to specific diagnosis in 33% of the cases. The most common diseases diagnosed by FB were malacia disorders (n: 32, 7%), aspirated foreign body (n: 30, 7%), endobronchial tuberculosis (n: 20, 5%), congenital airway anomalies (n: 14, 3%), mucus plugs (n: 14, 3%), pulmonary haemosiderosis (n: 12, 3%) and middle lobe syndrome (n: 11, 3%). During FB, only 6% of the patients had minor complications such as transient hypoxia, stridor and tachycardia. CONCLUSIONS: In our study, FB proved to be a safe and effective tool in evaluation of children with persistent or recurrent pneumonia. FB is indicated for children with recurrent or persistent pneumonia where the underlying diagnosis remains unclear even after non-invasive diagnostic tests.

PMID: 23438344 [PubMed - as supplied by publisher]

Intravenous immunoglobulin as adjuvant therapy for Wegener's granulomatosis.

Cochrane Database Syst Rev. 2013;1:CD007057

Authors: Fortin PM, Tejani AM, Bassett K, Musini VM

Abstract
BACKGROUND: Wegener's granulomatosis (WG) is a necrotizing small-vessel vasculitis that can affect any organ in the body but mainly affects the upper and lower respiratory tract, the kidneys, joints, skin and eyes. The current mainstay of remission induction therapy is systemic corticosteroids in combination with oral daily cyclophosphamide (CYC) which induces remission in 75% to 100% of cases. Although standard therapy is effective in inducing partial or complete remission, 50% of complete remissions are followed by at least one relapse. This is an update of a review first published in 2009.
OBJECTIVES: To determine if intravenous immunoglobulin (IVIg) adjuvant therapy provides a therapeutic advantage over and above treatment with systemic corticosteroids in combination with immunosuppressants for the treatment of WG.
SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 11). Trial databases were searched by the TSC for details of ongoing and unpublished studies. No date or language restrictions were applied.
SELECTION CRITERIA: Randomized controlled trials (RCTs), or quasi RCTs, or randomized cross-over trials. Participants had to be adults with a confirmed diagnosis of WG.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Relative risk was used to analyze dichotomous variables, and mean difference (MD) was used to analyze continuous variables.
MAIN RESULTS: We included one RCT with 34 participants who were randomly assigned to receive IVIg or placebo once daily in addition to azathioprine and prednisolone for remission maintenance. There were no significant differences between adjuvant IVIg and adjuvant placebo in mortality, serious adverse events, time to relapse, open-label rescue therapy, and infection rates. The fall in disease activity score, derived from patient-reported symptoms, was slightly greater in the IVIg group than in the placebo group at one month (MD 2.30; 95% Confidence interval (CI) 1.12 to 3.48, P < 0.01) and three months (MD 1.80; 95% CI 0.35 to 3.25, P = 0.01). There was a significant increase in total adverse events in the IVIg group (relative risk (RR) 3.50; 95% CI 1.44 to 8.48, P < 0.01).
AUTHORS' CONCLUSIONS: There is insufficient evidence from one RCT that IVIg adjuvant therapy provides a therapeutic advantage compared with the combination of steroids and immunosuppressants for patients with WG. Given the high cost of IVIg (one dose at 2 g/kg for a 70 kg patient = $8,400), it should be limited to treat WG in the context of a well conducted RCT powered to detect patient-relevant outcomes.

PMID: 23440811 [PubMed - in process]

Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.

Cochrane Database Syst Rev. 2013;1:CD009593

Authors: Steingart KR, Sohn H, Schiller I, Kloda LA, Boehme CC, Pai M, Dendukuri N

Abstract
BACKGROUND: Accurate and rapid detection of tuberculosis (TB) and drug resistance are critical for improving patient care and decreasing the spread of TB. Xpert® MTB/RIF assay (Xpert) is a rapid, automated test that can detect both TB and rifampicin resistance, within two hours after starting the test, with minimal hands-on technical time, but is more expensive than conventional sputum microscopy.
OBJECTIVES: To assess the diagnostic accuracy of Xpert for pulmonary TB (TB detection), both where Xpert was used as an initial test replacing microscopy, and where Xpert was used as an add-on test following a negative smear microscopy result.To assess the diagnostic accuracy of Xpert for rifampicin resistance detection where Xpert was used as the initial test, replacing conventional culture-based drug susceptibility testing.The population of interest was adults suspected of having pulmonary TB or multidrug-resistant TB (MDR-TB), with or without HIV infection.
SEARCH METHODS: We performed a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. We performed searches on 25 September 2011 and we repeated them on 15 December 2011, without language restriction.
SELECTION CRITERIA: We included randomized controlled trials, cross-sectional, and cohort studies that used respiratory specimens to compare Xpert with culture for detecting TB and Xpert with conventional phenotypic drug susceptibility testing for detecting rifampicin resistance.
DATA COLLECTION AND ANALYSIS: For each study, two review authors independently extracted a set of data using a standardized data extraction form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies using the QUADAS-2 tool. We carried out meta-analyses to estimate the pooled sensitivity and specificity of Xpert separately for TB detection and rifampicin resistance detection using a bivariate random-effects model. We estimated the median pooled sensitivity and specificity and their 95% credible intervals (CrI).
MAIN RESULTS: We identified 18 unique studies as eligible for this review, including two multicentre international studies, one with five and the other with six distinct study centres. The majority of studies (55.6%) were performed in low-income and middle-income countries. In 17 of the 18 studies, Xpert was performed by trained technicians in reference laboratories.When used as an initial test replacing smear microscopy (15 studies, 7517 participants), Xpert achieved a pooled sensitivity of 88% (95% CrI 83% to 92%) and pooled specificity of 98% (95% CrI 97% to 99%). As an add-on test following a negative smear microscopy result (14 studies, 5719 participants), Xpert yielded a pooled sensitivity of 67% (95% CrI 58% to 74%) and pooled specificity of 98% (95% CrI 97% to 99%). In clinical subgroups, we found the following accuracy estimates: the pooled sensitivity was 98% (95% CrI 97% to 99%) for smear-positive, culture-positive TB and 68% (95% CrI 59% to 75%) for smear-negative, culture-positive TB (15 studies); the pooled sensitivity was 80% (95% CrI 67% to 88%) in people living with HIV and 89% (95% CrI 81% to 94%) in people without HIV infection (four studies). For rifampicin resistance detection (11 studies, 2340 participants), Xpert achieved a pooled sensitivity of 94% (95% CrI 87% to 97%) and pooled specificity of 98% (95% CrI 97% to 99%). In a separate analysis, Xpert could distinguish between TB and nontuberculous mycobacteria (NTM) in clinical samples with high accuracy: among 139 specimens with NTM, Xpert was positive in only one specimen that grew NTM.In a hypothetical cohort of 1000 individuals suspected of having rifampicin resistance (a proxy for MDR-TB), where the prevalence of rifampicin resistance is 30%, we estimated that on average Xpert would wrongly identify 14 patients as being rifampicin resistant. In comparison, where the prevalence of rifampicin resistance is only 2%, we estimated that the number of individuals wrongly identified as rifampicin resistant would increase to 20, an increase of 43%.
AUTHORS' CONCLUSIONS: This review shows that Xpert used as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having TB, MDR-TB, or HIV-associated TB is sensitive and specific. Xpert may also be valuable as an add-on test following microscopy for patients who have previously been found to be smear-negative. An Xpert result that is positive for rifampicin resistance should be carefully interpreted and take into consideration the risk of MDR-TB in a given patient and the expected prevalence of MDR-TB in a given setting.Studies in this review mainly assessed sensitivity and specificity of the test when used in reference laboratories in research investigations. Most studies were performed in high TB burden countries. Ongoing use of Xpert in high TB burden countries will contribute to the evidence base on the diagnostic accuracy and clinical impact of Xpert in routine programmatic and peripheral health care settings, including settings where the test is performed at the point of care.

PMID: 23440842 [PubMed - in process]