Variations in very preterm birth rates in 30 high-income countries: are valid international comparisons possible using routine data?

OBJECTIVE: Concerns about differences in registration practices across countries have limited the use of routine data for international very preterm birth (VPT) rate comparisons. DESIGN: Population-based study. SETTING: Twenty-seven European countries, the United States, Canada and Japan in 2010. POPULATION: A total of 9 376 252 singleton births. METHOD: We requested aggregated gestational age data on live births, stillbirths and terminations of pregnancy (TOP) before 32 weeks of gestation, and information on registration practices for these births. We compared VPT rates and assessed the impact of births at 22-23 weeks of gestation, and different criteria for inclusion of stillbirths and TOP on country rates and rankings. MAIN OUTCOME MEASURES: Singleton very preterm birth rate, defined as singleton stillbirths and live births before 32 completed weeks of gestation per 1000 total births, excluding TOP if identifiable in the data source. RESULTS: Rates varied from 5.7 to 15.7 per 1000 total births and 4.0 to 11.9 per 1000 live births. Country registration practices were related to percentage of births at 22-23 weeks of gestation (between 1% and 23% of very preterm births) and stillbirths (between 6% and 40% of very preterm births). After excluding births at 22-23 weeks, rate variations remained high and with a few exceptions, country rankings were unchanged. CONCLUSIONS: International comparisons of very preterm birth rates using routine data should exclude births at 22-23 weeks of gestation and terminations of pregnancy. The persistent large rate variations after these exclusions warrant continued surveillance of VPT rates at 24 weeks and over in high-income countries. TWEETABLE ABSTRACT: International comparisons of VPT rates should exclude births at 22-23 weeks of gestation and terminations of pregnancy.

Lobar distribution in non-cystic fibrosis bronchiectasis predicts bacteriologic pathogen treatment.

Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged ≤64 years (OR = 0.969, p < 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged >64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes.

Outbreak of autoimmune disease in silicosis linked to artificial stone.

BACKGROUND: There is a well-established association between inhalational exposure to silica and autoimmune disease. We recently observed an outbreak of silica-related autoimmune disease among synthetic stone construction workers with silicosis referred for lung transplantation assessment. AIMS: To characterize the rheumatologic complications in silicosis within these highly exposed, clinically well-characterized patients. METHODS: We systematically reviewed data from all cases of silicosis due to synthetic stone dust referred to our pulmonary institute for lung transplant assessment, which represents the national centre for all such referrals. In addition to silicosis-specific data, we extracted data relevant to the clinical and serological manifestations of autoimmune diseases present in these patients. RESULTS: Of 40 patients in our advanced silicosis national data, we identified nine (23%) with findings consistent with various autoimmune diseases. Among these nine, three also had findings consistent with pulmonary alveolar proteinosis. Based on an expected autoimmune disease prevalence of 3% (based on the upper-end estimate for this group of diseases in European international data), the proportion of disease in our group represents a >7-fold excess (prevalence ratio 7.5; 99% confidence interval 2.6-16.7). CONCLUSIONS: These cases underscore the strong link between silicosis and multiple distinct syndromes of autoimmune diseases. Vigilance is warranted for the recognition of autoimmune complications in persons with known silicosis; so too is consideration of the occupational exposure history in persons presenting with manifestations of autoimmune disease.

Fear of childbirth in nulliparous and multiparous women: a population-based analysis of all singleton births in Finland in 1997-2010.

OBJECTIVE: To identify risk factors for fear of childbirth (FOC) according to parity and socioeconomic status, and to evaluate associations between FOC and adverse perinatal outcomes. DESIGN: A cohort study. SETTING: The Finnish Medical Birth Register. POPULATION: All 788 317 singleton births during 1997-2010 in Finland. METHODS: Fear of childbirth was defined according to the International Classification of Diseases code O99.80, and its associations with several risk factors and perinatal outcomes were analysed by multivariable logistic regression. MAIN OUTCOME MEASURES: Prevalence of, risk factors for and outcomes of FOC. RESULTS: Fear of childbirth was experienced by 2.5% of nulliparous women and 4.5% of multiparous women. The strongest risk factors for FOC in nulliparous women were depression [adjusted odds ratio (aOR), 6.35; 95% confidence interval (CI), 5.25-7.68], advanced maternal age (aOR, 3.78; 95% CI, 3.23-4.42) and high or unspecified socioeconomic status. In multiparous women, the strongest risk factors for FOC were depression (aOR, 5.47; 95% CI, 4.67-6.41), previous caesarean section (CS) (aOR, 3.02; 95% CI, 2.93-3.11) and high or unspecified socioeconomic status. Among both nulliparous and multiparous women, FOC was associated with higher rates of CS (3.3-fold and 4.5-fold higher, respectively) and a lower incidence of low birthweight (<2500 g), small for gestational age babies, preterm birth and low Apgar scores at 1 minute. CONCLUSIONS: High and unspecified socioeconomic status, advanced maternal age and depression are predisposing factors for FOC regardless of parity. Among multiparous women, a previous CS increases vulnerability to FOC. FOC is associated with increased rates of CS, but does not adversely affect other pregnancy outcomes.

Comparison of isoniazid monoresistant tuberculosis with drug-susceptible tuberculosis and multidrug-resistant tuberculosis.

Limited data exist about the clinical characteristics of Mycobacterium tuberculosis (TB) isolates with resistance to isoniazid (IZN). We describe the demographic and clinical characteristics and risk factor information for persons with IZN monoresistant (resistant to isoniazid) TB compared with drug-susceptible TB and multidrug-resistant (MDR) TB. From 2002 to 2009, 590 cases of TB were diagnosed. Of these, 44 (7.5%) developed MDR-TB and 38 (6.4%) had IZN monoresistant TB. Among the IZN monoresistant TB patients, more common demographic characteristics were former resident of the Soviet Union immigrant, smoker, and previous history of TB (p = 0.005, 0.025, and 0.005, respectively), while HIV, weight loss, and hemoptysis were less common (p = 0.005 for all parameters). The mean length of treatment was 24 ± 4 months for MDR-TB, 10 ± 3 months for IZN monoresistant TB cases, and 8 ± 2 months for all other TB cases. The directly observed therapy (DOT) rate was similar in all three groups. However, treatment failure, completion of TB treatment, and mortality were all similar in drug-susceptible TB and higher in MDR-TB. In multivariate analysis, only a history of previous TB (odds ratio [OR] 1.4; 95% confidence interval [CI]: 1.2-1.6) was significantly associated with IZN monoresistant TB. IZN monoresistant TB has distinct characteristics. However, the length of treatment and outcome are similar to drug-susceptible TB cases.

Does side matter? Effect of single lung transplant laterality on outcomes.

BACKGROUND: Previous works have suggested that recipients of left single lung transplant (SLT) have a worse outcome than those receiving right SLT. We evaluated the effect of SLT laterality on outcomes. METHODS: We performed a retrospective study of SLT recipients followed up at our center. One hundred and nineteen patients were reviewed (53 left SLT, 66 right SLT). We extracted data on lung function, exercise capacity, relative graft perfusion, airway complications, acute rejection episodes, infections and mortality. RESULTS: There was no significant difference between right and left lung recipients with regard to baseline demographic and physiological characteristics. Lung function, exercise capacity and relative graft perfusion improved in both groups following transplantation. We observed a higher graft perfusion in right-sided grafts compared to left ( P = 0.048). There was no significant difference between the two groups in physiological outcomes, rejection or infection episodes, the presence of chronic rejection or mortality. We observed a statistically higher need for bronchial stent insertion during early follow-up amongst the left lung recipients ( P = 0.022). CONCLUSIONS: Both right and left lungs are equally suitable for transplantation. The left-sided bronchial anastomosis may be more vulnerable to complications.

Biologic lung volume reduction therapy for advanced homogeneous emphysema.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Decline in pulmonary function in patients with breast cancer receiving dose-dense chemotherapy: a prospective study.

BACKGROUND: Prompted by complaints of dyspnea in breast cancer patients receiving adjuvant dose-dense chemotherapy (DDC), we sought to evaluate the possible association of DDC with pulmonary dysfunction. PATIENTS AND METHODS: A total of 34 consecutive patients receiving adjuvant DDC were enrolled. The chemotherapy regimen consisted of i.v. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) (AC) every 14 days x4 with growth factor support followed by weekly i.v. paclitaxel 80 mg/m(2) x12. The following parameters were prospectively measured before and after the AC protocol (P1, P2) and at completion of paclitaxel treatment (P3): presence of dyspnea, blood pressure, pulse rate, hemoglobin, erythrocyte sedimentation rate, C-reactive protein level, cardiac ejection fraction, and pulmonary function. Repeated measures analysis was used to evaluate differences among the time points, and paired t-test was used to evaluate differences between consecutive time points. RESULTS: Although only five patients (15%) complained of dyspnea, there was a significant decrease in mean carbon monoxide diffusing capacity (DLCO), in all patients from P1 (22.09 ml/min/mmHg) to P3 (15 ml/min/mmHg) and in 29 of 32 patients (90.6%) from P1 to P2 (15.96 ml/min/mmHg) (P<0.001). CONCLUSIONS: DDC is associated with a statistical significant reduction in DLCO. Awareness of this potential toxicity may be important in women with preexisting lung disease.

Pulmonary Mycobacterium simiae infection: comparison with pulmonary tuberculosis.

To identify the clinical and radiological features distinguishing Mycobacterium simiae respiratory infection from pulmonary tuberculosis, the demographics, underlying conditions, and clinical and radiological findings of 121 consecutive patients with pulmonary tuberculosis and 102 with M. simiae respiratory infection were compared retrospectively. In the M. simiae group, the patients were older (mean age 69 +/- 16 years vs. 47 +/- 21 years, p = 0.0001), with a female predominance (62% vs. 45%, p = 0.008). Only 4% were of Ethiopian origin compared to 25% of the tuberculosis group (p = 0.0001). M. simiae infection was associated with significantly higher rates of smoking history, underlying chronic obstructive pulmonary disease, zero human immunodeficiency virus (HIV) infection compared to 10% in the tuberculosis group (p = 0.001), blunted symptoms, and noncavitary infiltrates in the lower/middle lobes on chest X-ray. HIV-negative patients with M. simiae respiratory infection are distinguishable from patients with pulmonary tuberculosis by several demographic, clinical, and radiological features. These findings have important diagnostic and therapeutic implications.

Absence of human herpesvirus 8 DNA sequences in lung biopsies from Israeli patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary hypertension is a severe pulmonary vascular disease leading to rapid deterioration and death. Histological and clinical evidence suggests that smooth muscle proliferation is part of the pathogenesis of the disease. Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus that is implicated in malignancies and in Kaposi's sarcoma. Recently, the association of HHV-8 with idiopathic pulmonary arterial hypertension (PAH) has been found. OBJECTIVE: The aim of this study was to investigate the presence of HHV-8 in the lung tissue of Israeli patients with PAH. METHOD: The presence of HHV-8 sequences was investigated by polymerase chain reaction examination in 6 biopsies of patients with pulmonary hypertension. Three patients had idiopathic pulmonary hypertension, 2 patients pulmonary venoocclusive disease, and 1 patient pulmonary hypertension associated with mixed connective tissue disease. RESULT: We did not find any association between HHV-8 and PAH in these Israeli patients, as all the samples were negative for polymerase chain reaction. CONCLUSION: Our findings, together with the epidemiological data of HHV-8 prevalence and incidence rates of Kaposi's sarcoma and PAH in Israel, provide further evidence which argues against an association between HHV-8 infection and PAH.

Effectiveness of Rabbit Antithymocyte Globulin in Chronic Lung Allograft Dysfunction.

BACKGROUND: Rabbit antithymocyte globulin (rATG) therapy has been shown to be beneficial in lung transplant recipients as induction therapy for treating acute lung rejection; however, its role in chronic lung rejection has been reported only rarely. We evaluated the effectiveness of rATG therapy in slowing the progression of chronic lung allograft dysfunction (CLAD) syndrome. METHODS: We conducted a retrospective review of 25 lung transplant patients with CLAD who received rATG therapy in the Pulmonary Institute of Rabin Medical Center, Israel, between May 2005 and February 2016. Response to treatment was divided into 2 categories: stabilization, defined as a halting of the decline of forced expiratory volume in 1 second (FEV1) for ≥6 months after rATG therapy, and deterioration, defined as showing a continued decline in FEV1. RESULTS: Of 25 subjects, 8 (32%) were categorized as part of the stabilization group and 17 (68%) were categorized as showing continued deterioration. The stabilization group was older (61 ± 8 vs 44 ± 19 years) and showed longer survival rate after rATG therapy (930 ± 385 vs 414 ± 277 days). The stabilization group also demonstrated a lower mean white blood cell count (7.9 ± 1.8 vs 8.5 ± 2.9 × 10(9) cells/L) and lymphocyte count (0.37 ± 0.1 vs 0.55 ± 0.3 × 10(9) cells/L) during rATG treatment. The stabilization group also demonstrated a higher FEV1 after lung transplantation (91% ± 21% vs 75% ± 15.4%), at the beginning of rATG therapy (51% ± 11% vs 39% ± 9.6%) and at 6 months after rATG therapy follow-up (51% ± 9.1% vs 28% ± 7.6%). CONCLUSIONS: rATG was effective in stabilizing rejection progression in approximately one-third of our patients with CLAD. rATG therapy should be considered early in the course of CLAD. Randomized, controlled studies should be considered to confirm these findings.

Normal D-dimer levels in patients with latent tuberculosis infection.

Studies have demonstrated a link between acute pulmonary tuberculosis and a hypercoagulable state, but there are no data on the coagulation state of patients with latent tuberculosis infection (LTI). The present prospective observational study was designed to help fill this gap. The sample included 84 patients (high school students and adults) with suspected LTI referred for the purified protein derivative (PPD) test. Results were read according to the criteria of the American Thoracic Society. Blood samples were collected at admission and assayed for D-dimer, the marker of the coagulation state, with the quantitative Miniquant test. D-dimer values were correlated with the PPD status and clinical parameters. Fifty-seven patients tested positive for LTI and 27 tested negative. There was no significant difference in D-dimer level between these groups (341 +/- 106 and 360 +/- 60 microg/ml, respectively). No significant correlation was found between D-dimer level and PPD status, patient age or occupation (health care worker or not), or clinical indication for the tuberculin test. The normal D-dimer levels in this series suggest that low-level inflammations such as LTI do not lead to a hypercoagulable state.

Living related donation in lung transplantation. Ethical considerations.

Lung transplantation has become an established rescue therapy for patients with end-stage disease. The major problem, however, is the shortage of organ donors. Living related donation has been successful in kidney and liver transplantation and, recently, in lobar lung transplantation as well. The main ethical dilemma is whether we should risk a parent family member in order to save a child or relative. This dilemma can be taken to the extreme in a case in which pneumonectomy from a live donor can save a patient who is in need of single lung transplantation, a procedure that has not yet been performed, although technically feasible. We discuss the ethical aspects of such a procedure from the perspectives of the donor, the recipient, and the medical team.

Mortality in elderly patients with thermoregulatory failure.

Fifty-four elderly patients with thermoregulatory failure were evaluated retrospectively. The most commonly associated cause was underlying sepsis, which occurred in 78% of cases. Underlying conditions that increased the incidence of hypothermia were hypoproteinemia (50%), cachexia (30%), and neuroleptic medications (21%), most commonly thioridazine. Digoxin toxicity was a common finding (20% of all cases). One third of the patients developed hypothermia in warm months and half of them developed it while in the hospital. Patients who presented with hypothermia from out of the hospital had lower temperatures, were more bradycardic and hemoconcentrated, and died more rapidly than the in-hospital group. This could be explained by lower outside temperature or delay in diagnosis and treatment of the underlying disease. The overall mortality rate was extremely high (74%) in both groups. The mortality rate was not affected by age, sex, or degree of hypothermia. We conclude that thermo-regulatory failure in the elderly can occur in warm as well as cold environments or climates. The development of hypothermia in elderly patients should be promptly treated as sepsis unless proven otherwise, in light of the poor prognosis of this condition.

Effect of theophylline on erythrocytosis in chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) tend to develop secondary erythrocytosis to compensate for their chronic hypoxia. Theophylline has recently been shown to reduce hematocrit and erythropoietin blood levels in normal subjects and in patients with erythrocytosis after renal transplantation. OBJECTIVE: To determine whether theophylline may be used to lower the hematocrit in patients with COPD. METHODS: Two hundred four patients with COPD were studied retrospectively and 10 patients prospectively (8 starting treatment with the drug [group 1] and 2 who suspended its long-term use [group 2]) for the correlation between theophylline therapy and hematocrit and erythropoietin level. RESULTS: In the patients studied retrospectively, lower hematocrits were found in the theophylline-treated than in the untreated patients (0.43 +/- 0.006 vs 0.46 +/- 0.007, respectively; P < .002). Twelve untreated patients and 2 of those treated with theophylline had hematocrits above 52%. Oxygen saturation levels were similar in both groups, and exclusion of patients with oxygen saturation lower than 88% did not change the pattern, suggesting that the effect of theophylline could not be entirely explained by improved oxygen availability. Seven of the 8 patients studied prospectively in group 1 (P < .02) and the 2 patients in group 2 showed inverse correlations between hematocrits and theophylline administration. A similar pattern was observed with serum erythropoietin levels in 5 of 7 patients studied. The effects were reproducible on rechallenge in 3 of the 4 patients in group 1 and the 2 patients in group 2. CONCLUSIONS: Theophylline may have a beneficial effect in treatment and prevention of erythrocytosis in patients with COPD.

Infectious complications in heart-lung transplantation. Analysis of 200 episodes.

BACKGROUND: Infection remains an important cause of morbidity and mortality in heart-lung transplant recipients. This study was designed to assess the frequency, type, and timing of infection in heart-lung transplant recipients. METHODS: A retrospective analysis of 200 episodes of serious infections occurring in 73 heart-lung recipients at Stanford (Calif) University Medical Center between 1981 and 1990. RESULTS: Bacterial infections accounted for half of all infections, with the highest incidence in the first month after transplantation. Fungal infections (14%) were also common in the first month. Cytomegalovirus was the most common viral agent (15%), occurring primarily in the second month after transplantation. Other viruses (herpes simplex, adenovirus, and respiratory syncytial virus) accounted for a further 15% of total infections. Pneumocystis carinii infections were common 4 to 6 months after transplantation, and Nocardia typically infected recipients later than 1 year after transplantation. There was no significant difference in incidence of infections between patients receiving triple (cyclosporine, prednisone, immuran) or double (cyclosporine and prednisone) immunosuppression therapy. Mortality due to infection accounted for 40% of all deaths. CONCLUSIONS: Knowledge of the incidence and timing of infection should help in the prevention, early detection, and initiation of therapy in these patients.

Cyclosporin drug-interaction-induced rhabdomyolysis. A report of two cases in lung transplant recipients.

In rare cases the use of cyclosporin in transplant patients can cause myopathic changes. We describe two patients, the recipients of lung transplants, who developed severe reversible rhabdomyolysis associated with cyclosporin drug-drug interaction.

Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii infections in heart-lung and lung transplantation--how effective and for how long?

Pneumocystis carinii pneumonia (PCP) is a common clinical problem in the setting of organ transplantation, particularly in heart-lung and lung allograft recipients. Without prophylactic measurements, the incidence of P carinii pneumonia can reach up to 88% of heart-lung transplant recipients. We conducted a retrospective analysis of the Stanford heart-lung and lung transplant experience in order to assess the efficacy of the prophylactic therapy and to try to define the duration of therapy necessary for prevention. During a 9-year period 82 heart-lung and 13 single-lung transplants were performed. Of the patients not on prophylaxis therapy 27% (13 patients) developed P carinii infection as compared with 0% of patients on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. The incidence of PCP infection peaked between 3 and 6 months posttransplantation. No case of infection was observed before the 7th week posttransplant. PCP was more common following induction immunosuppression with OKT3 as compared with RATG (P less than 0.05). All cases of infections later than one year posttransplant were associated with recent increase in the immunosuppression regimen with high-dose corticosteroids for treatment of acute or chronic (obliterative bronchiolitis) rejection. Although our study is retrospective and based on various immunosuppressive and diagnostic technique periods, it seems that TMP-SMX is highly effective in preventing PCP infections in heart-lung and lung transplant recipients. Twelve months of therapy is probably a sufficient length of therapy if immunosuppressive therapy is stable. However, whenever augmentation in the immunosuppression regimen is indicated, prophylactic therapy should promptly be restarted.

Gastric perforation due to mucormycosis after heart-lung and heart transplantation.

BACKGROUND: Gastrointestinal complications are a well-documented source of morbidity and mortality after heart and lung transplantation. METHODS: We report on two patients who presented with gastric perforation caused by mucormycosis during the first 2 months after heart-lung and heart transplantation. RESULTS: In the first patient, the clinical presentation was insidious and the diagnosis was made at an advanced stage of the disease. Despite surgery and aggressive antifungal treatment, the patient died. In the second patient, the diagnosis was made promptly, but despite antifungal treatment, he presented with gastric perforation within a week. CONCLUSIONS: These cases illustrate that fungal invasive disease may be a cause of early gastrointestinal perforation after solid organ transplantation.