bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis
Authors: Nagano J. , Iyonaga K. , Kawamura K. , Yamashita A. , Ichiyasu H. , Okamoto T. , Suga M. , Sasaki Y. , Kohrogi H.
Published: February 2006

Idiopathic pulmonary fibrosis has a poor prognosis and few efficacious treatments. The immunosuppressant cyclosporin A has been shown to inhibit tumour growth factor (TGF)-β-induced collagen depositionin vitro, and is widely used in Japan as a potent antifibrotic agent. Tacrolimus (FK506) is another attractive immunosuppressant, which may be useful in the treatment of pulmonary fibrosis. The aim of the present study was to elucidate the antifibrotic effect of FK506.

The inhibitory effect of FK506 on collagen synthesis in cultured lung fibroblastic cells, TIG-3-20, and its antifibrotic effect on bleomycin (BLM)-induced pulmonary fibrosis in mice was investigated.

FK506 inhibited TGF-β-induced collagen synthesis, and suppressed the expression of TGF-β type I receptor (TβR-I) in TIG-3-20 cells. Consistent with thein vitrofindings, FK506 treatment starting on day 6 attenuated BLM-induced pulmonary fibrosis, in part,viareduced TβR-I expression. FK506 treatment in the acute BLM injury phase unexpectedly increased pro-inflammatory cytokine levels in bronchoalveolar lavage fluid and enhanced lung injury, resulting in poor survival.

In conclusion, the present results suggest that FK506 has a potent antifibrotic effect and may be useful for the treatment of pulmonary fibrosis, although its use in the acute inflammatory phase may exacerbate lung injury.
Prevalence of oxygen desaturation and use of oxygen at home in adults at sea level and at moderate altitude
Authors: Perez-Padilla R. , Torre-Bouscoulet L. , Muiño A. , Marquez M. N. , Lopez M. V. , de Oca M. M. , Talamo C. , Menezes A. M. B.
Published: February 2006

The aim of this study was to determine the prevalence of oxygen desaturation in adults aged ≥40 yrs as altitude above sea level increases.

A population-based, cross-sectional study with a multistage cluster sampling of 1,063 subjects from metropolitan Mexico City (Mexico; 2,240 m above sea level), 1,357 from Caracas (Venezuela; 950 m) and 943 from Montevideo (Uruguay; 35 m). The mean of six measurements of arterial oxygen saturation (SP,O2) was estimated using a pulse oximeter.

MeanSP,O2decreased with altitude. No subject from Montevideo had a meanSP,O2≤88%. Prevalence of subjects withSP,O2≤88%, a common criterion used for oxygen prescription, was 1.0% in Caracas and 6.0% in Mexico City. Additional predicting factors for hypoxaemia in multiple regression models were age, body mass index and a low forced expiratory volume in one second as a percentage of the predicted value. In Mexico City and Caracas, <10% of the hypoxaemic subjects reported use of domiciliary oxygen, whereas at least half of the subjects reporting use of oxygen at home had a restingSP,O2>88%.

In conclusion, the prevalence of hypoxaemia was closely related to altitude. Priorities for oxygen prescription must be defined in moderate altitudes because it is unfeasible to provide it to all subjects fulfilling the criteria commonly used.
Fatal haemoptysis in a case of lymphomatoid granulomatosis treated with rituximab
Authors: Jaffre S. , Jardin F. , Dominique S. , Duet E. , Hubscher Ph. , Genevois A. , Corne F. , Bota S. , Nouvet G. , Thiberville L.
Published: February 2006

Lymphomatoid granulomatosis is a rare angiocentric and angiodestructive disease, which commonly involves the lungs but also the brain, kidneys, liver and skin. This report describes the case of a 33-yr-old female with an aggressive form of lymphoid granulomatosis treated with an anti-CD20 antibody. Dramatic radiological improvement was seen at the fourth week. However, the patient died at home 1 month after the last rituximab administration from a massive haemoptysis.
Telomere shortening in smokers with and without COPD
Authors: Morlá M. , Busquets X. , Pons J. , Sauleda J. , MacNee W. , Agustí A. G. N.
Published: February 2006

Telomeres are complex DNA–protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating lymphocytes. The present study investigated whether this effect was further amplified in smokers who develop chronic obstructive pulmonary disease.

Telomere length was determined by fluorescencein situhybridisation in circulating lymphocytes harvested from 26 never-smokers, 24 smokers with normal lung function and 26 smokers with moderate-to-severe airflow obstruction (forced expiratory flow in one second 48±4% predicted).

In contrast to never-smokers, telomere length significantly decreased with age in smokers. There was also a dose–effect relationship between the cumulative long-life exposure to tobacco smoking (pack-yrs) and telomere length. The presence and/or severity of chronic airflow obstruction did not modify this relationship.

The results of the current study confirm that smoking exposure enhances telomere shortening in circulating lymphocytes. It also demonstrates a dose–effect relationship between exposure to tobacco smoking and telomere length, but failed to show that this effect is amplified in smokers who develop chronic obstructive pulmonary disease.
A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension
Authors: Robbins I. M. , Kawut S. M. , Yung D. , Reilly M. P. , Lloyd W. , Cunningham G. , Loscalzo J. , Kimmel S. E. , Christman B. W. , Barst R. J.
Published: February 2006

Idiopathic pulmonary arterial hypertension (IPAH) is characterised byin situthrombosis and increased thromboxane (Tx) A2synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH.

A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2and urinary metabolites of TxA2and prostaglandin I2(Tx-M and PGI-M, respectively) were assessed.

A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results.

In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed.
Simplified stepwise management of primary spontaneous pneumothorax: a pilot study
Authors: Marquette C-H. , Marx A. , Leroy S. , Vaniet F. , Ramon P. , Caussade S. , Smaiti N. , Bonfils C.
Published: February 2006

In primary spontaneous pneumothorax (PSP) requiring intervention, removal of air from the pleural space can be achieved by manual needle aspiration or by pleural drainage after insertion of a chest tube. This study aimed to evaluate the efficacy and safety of a serial-steps approach with a single system (small-calibre catheter/Heimlich valve) in a homogeneous population of patients with a first episode of PSP.

All patients had an 8.5 F distally multiperforated polyurethane pigtail catheter insertedviathe anterior route, at the bedside without any guidance, using the Seldinger technique. A one-way Heimlich valve was connected to the catheter, allowing the air to flow spontaneously outwards for 24–48 h. Thereafter, if the lung failed to re-expand wall suction was applied. Patients with an air leak persisting for >4 days were referred for surgery. Primary end-points were success rates at 24 h and 1 week, and 1 yr recurrence-free survival.

In total, 41 consecutive patients entered the study. They were typically thin, young, smoking males. No procedure-related complications were observed. The need for pain relief medication was minimal. Within the first 24 h, most of the patients were able to walk around and half of them were able to take a shower with their catheter in place. The 24-h and 1-week success rates were 61 and 85%, respectively, and the actuarial 1-yr recurrence rate was 24%. Four patients underwent surgical pleurodesis because of a persistent air leak. The length of stay when excluding the four surgical cases was 2.3±1.3 days.

When 24-h and 1-week success rates and recurrence at 12 months were taken as end-points, the method described here is as effective as simple manual needle aspiration or a conventional chest tube thoracotomy. These results support further studies assessing this “one system, serial-steps approach” in an outpatient management algorithm.
Changes in active and passive smoking in the European Community Respiratory Health Survey
Authors: Janson C. , Künzli N. , de Marco R. , Chinn S. , Jarvis D. , Svanes C. , Heinrich J. , Jõgi R. , Gislason T. , Sunyer J. , Ackermann-Liebrich U. , Antó J. M. , Cerveri I. , Kerhof M. , Leynaert B. , Luczynska C. , Neukirch F. , Vermeire P. , Wjst M. , Burney P.
Published: February 2006

The aim of the present investigation was to study changes and determinants for changes in active and passive smoking.

The present study included 9,053 adults from 14 countries that participated in the European Community Respiratory Health Survey II. The mean follow-up period was 8.8 yrs. Change in the prevalence of active and passive smoking was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. Determinants of change were analysed and the results expressed as adjusted hazard risk ratio (HRR) or odds ratio (OR).

The prevalence of active smoking declined by 5.9% (5.1–6.8) and exposure to passive smoking in nonsmokers declined by 18.4% (16.8–20.0). Subjects with a lower educational level (HRR: 0.73 (0.54–0.98) and subjects living with a smoker (HRR: 0.45 (0.34–0.59)) or with workplace smoking (HRR: 0.69 (0.50–0.95)) were less likely to quit. Low socio-economic groups were more likely to become exposed (OR: 2.21 (1.61–3.03)) and less likely to cease being exposed to passive smoking (OR: 0.48 (0.37–0.61)).

In conclusion, the quitting rate was lower and the risk of exposure to passive smoking higher among subjects with lower socio-economic status. Exposure to other peoples smoking decreased quitting rates and increased the risk of starting to smoke.
Circulating haemopoietic and endothelial progenitor cells are decreased in COPD
Authors: Palange P. , Testa U. , Huertas A. , Calabrò L. , Antonucci R. , Petrucci E. , Pelosi E. , Pasquini L. , Satta A. , Morici G. , Vignola M. A. , Bonsignore M. R.
Published: February 2006

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD).

Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean±sd68±8 yrs; forced expiratory volume in one second: 48±12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8) were measured.

Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3±2.5versus10.3±4.2 cells·µL−1), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30–50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-α levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies.

In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.
Can heart rate variation rule out sleep-disordered breathing in heart failure?
Authors: Vazir A. , Dayer M. , Hastings P. C. , McIntyre H. F. , Henein M. Y. , Poole-Wilson P. A. , Cowie M. R. , Morrell M. J. , Simonds A. K.
Published: February 2006

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne–Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF.

In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles.

Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea–hypopnoea index >20 events·h−1and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea–hypopnoea cut-off of 30 events·h−1.

In conclusion, these results suggest that spectral analysis of heart rate may be useful as a “rule-out test” for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.
Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations
Authors: Jayaram L. , Pizzichini M. M. , Cook R. J. , Boulet L-P. , Lemière C. , Pizzichini E. , Cartier A. , Hussack P. , Goldsmith C. H. , Laviolette M. , Parameswaran K. , Hargreave F. E.
Published: February 2006

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal.

A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils ≤2%; symptoms and spirometry were used to identify clinical control, exacerbations and other treatments. Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS, thus removing bias. First, the minimum treatment to maintain control was identified in 107 patients (Phase 1) and then this treatment was continued (Phase 2) for the remaining of the 2 yrs. The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation. The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed.

The duration and number of exacerbations in Phase 1 were similar in both groups. In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS (62.7%) and 47 (37.3%) in the SS groups. The majority of the 126 exacerbations (101; 80.1%) were mild. The majority of the 102 exacerbations, where sputum examination was performed before any treatment (n = 70), were noneosinophilic. In the SS patients, the time to the first exacerbation was longer (by 213 days) especially in those considered to need treatment with a long acting β2-agonist (by 490 days), the relative risk ratio was lower (by 49%), and the number of exacerbations needing prednisone was reduced (5versus15). This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone >250 μg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups.

Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.
Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia
Authors: Rello J. , Rodriguez A. , Torres A. , Roig J. , Sole-Violan J. , Garnacho-Montero J. , de la Torre M. V. , Sirvent J. M. , Bodi M.
Published: March 2006

The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included <20% of critically ill patients.

The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP.

In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01–1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63–4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged ≥70 yrs, smokers and who had chronic heart disease orPseudomonas aeruginosawere higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19–12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18–4.53) and shock (OR 3.53; 95% CI 1.31–9.71).

In conclusion, chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.
La belle indifférencein conversion symptoms and hysteria
Authors: Stone Jon , Smyth Roger , Carson Alan , Warlow Charles
Published: February 2006

Background

La belle indifférencerefers to an apparent lack of concern shown by some patients towards their symptoms. It is often regarded as typical of conversion symptoms/hysteria.

Aims

To determine the frequency ofla belle indifférencein studies of patients with conversion symptoms/hysteria and to determine whether it discriminates between conversion symptoms and symptoms attributable to organic disease.

Method

A systematic review of all studies published since 1965 that have reported rates ofla belle indifférencein patients with conversion symptoms and/or patients with organic disease.

Results

Atotal of 11 studies were eligible for inclusion. The median frequency ofla belle indifférencewas 21 % (range 0–54%) in 356 patients with conversion symptoms, and 29% (range 0–60%) in 157 patients with organic disease.

Conclusions

The available evidence does not support the use ofla belle indifférenceto discriminate between conversion symptoms and symptoms of organic disease. The quality of the published studies is poor, with a lack of operational definitions and masked ratings.La belle indifférenceshould be abandoned as a clinical sign until both its definition and its utility have been clarified.
Longitudinal investigation into childhood-and adolescence-onset depression: Psychiatric outcome in early adulthood
Authors: Dunn Valerie , Goodyer Ian M.
Published: February 2006

Background

Major depression in childhood or adolescence increases the risk of affective disorder in adulthood. The precise nature and course of the subsequent disorder remain unclear.

Aims

To investigate long-term psychiatric outcome of school-age depression in community and clinic samples.

Method

A group of 113 young adults were followed up after a mean of 7.8 years (s.e.=15).

Results

Groups with persistent and recurrent depression were identified. Recurrence of affective disorder was similar in clinic and community groups. The clinic group had significantly longer index episodes; these were predicted by an early psychiatric history, longer episode duration before treatment and greater impairment. Being female, having higher self-report depression scores and comorbidity at index episode predicted earlier recurrence. Males were more likely to have persistent depression.

Conclusions

Prognosis is similar in young people with depression from community and clinical samples. Boys from a clinical sample are at higher risk than girls of becoming persistently and severely mentally ill.
Lifetime suicide rates in treated schizophrenia: 1875–1924 and 1994–1998 cohorts compared
Authors: Healy D. , Harris M. , Tranter R. , Gutting P. , Austin R. , Jones-Edwards G. , Roberts A. P.
Published: February 2006

Background

Recent interest in suicide rates in schizophrenia has been considerable.

Aims

To establish the lifetime suicide rate from the pre-chlorpromazineera and to compare this with recent lifetime suicide rates for schizophrenia.

Method

We have compared suicide and suicide attempt rates for 741 admissions for schizophrenia and 1303 admissions for psychoses to the North Wales Asylum between 1875 and 1924, with first admissions for psychosis in North West Wales between 1994 and 1998.

Results

The suicide rate in schizophrenia between 1875 and 1924 was 20 per 100 000 hospital years, a lifetime rate of less than 0.5%. The suicide rate for all psychoses was 16 per 100 000 hospital years. Current rates of suicide for schizophrenia and other psychoses appear 20-fold higher.

Conclusions

These findings point to an increase in suicide rates for patients with schizophrenia.
Alcohol consumption and suicide among middle-aged men in Japan
Authors: Akechi Tatsuo , Iwasaki Motoki , Uchitomi Yosuke , Tsugane Shoichiro
Published: February 2006

Background

Few studies have investigated large population-based cohorts for an association between alcohol consumption and suicide.

Aims

To investigate the possible association between alcohol intake and suicide.

Method

We used nationwide population-based cohort data from the Japan Public Health Centre-Based Prospective Study cohort. Atotal of 43 383 men aged 40–69 years participated. Death from suicide was defined according to ICD–10 as codes X60-X84.

Results

Duringthe367817person-years of follow-up, there were 168 suicides. Compared with occasional drinkers, the pooled multivariate relative risk (RR; with 95% CI) of suicide for non-drinkers and regular heavy drinkers was 2.3 (1.2–4.6) and 2.3 (1.2–4.7) respectively. The RR increased with the amount of alcohol consumed (P for trend =0.004).

Conclusions

There is a U-shaped association between alcohol consumption and subsequent suicide.
Comorbid substance use and age at onset of schizophrenia
Authors: Barnes Thomas R. E. , Mutsatsa Stanley H. , Hutton Sam B. , Watt Hilary C. , Joyce Eileen M.
Published: February 2006

Background

Substance use may be a risk factor for the onset of schizophrenia.

Aims

To examine the association between substance use and age at onset in a UK, inner-city sample of people with recent-onset schizophrenia.

Method

The study sample consisted of 152 people recruited to the West London First-Episode Schizophrenia Study. Self-reported data on drug and alcohol use, as well as information on age at onset of psychosis, were collected. Mental state, cognition (IQ, memory and executive function) and social function were also assessed.

Results

In total, 60% of the participants were smokers, 27% reported a history of problems with alcohol use, 35% reported current substance use (not including alcohol), and 68% reported lifetime substance use (cannabis and psychostimulants were most commonly used). Cannabis use and gender had independent effects on age at onset of psychosis, after adjusting for alcohol misuse and use of other drugs.

Conclusions

The strong association between self-reported cannabis use and earlier onset of psychosis provides further evidence that schizophrenia may be precipitated by cannabis use and/or that the early onset of symptoms is a risk factor for cannabis use.
Suicide now and then … an elusive comparison
Authors: Turner Trevor
Published: February 2006

Comparing suicide rates between Victorian and modern times, and the impact of the asylum, should enable a useful historical perspective on how effective our treatment approaches really are. Difficulties include clarifying the ‘social geography’, the underlying diagnoses, the reasons for admission and the reliability of casebook data and follow-up arrangements.
Inconsistency in reporting potentially traumatic events
Authors: Hepp Urs , Gamma Alex , Milos Gabriella , Eich Dominique , Ajdacic-Gross Vladeta , Rössler Wulf , Angst Jules , Schnyder Ulrich
Published: February 2006

Background

Research on posttraumatic stress disorder (PTSD) relies mainly on self-reports of exposure to trauma and its consequences.

Aims

To analyse the consistency of the reporting of potentially traumatic events (PTEs) over time.

Method

A community-based cohort, representative of the canton of Zurich, Switzerland, was interviewed at the ages of 34–35 years (in 1993) and 40–41 years (in 1999). A semi-structured diagnostic interview, including a section on PTSD, was administered.

Results

Of the 342 participants who attended both interviews, 169 reported some PTE (1993,n=110; 1999,n=120). In 1999, 56 participants (33.1%) reported for the first time PTEs that actually occurred before 1993, but which had not been reported in the 1993 interview. In total, 68 participants (40.2%) who had reported a PTE in 1993 did not report it in 1999. The overall frequency of inconsistent reporting was 63.9%.

Conclusions

The high level of inconsistency in the reporting of PTEs has implications for therapy as well as for research.
Impact of psychiatric disturbance on identifying psychiatric disorder in relatives: study of mothers and daughters
Authors: Coelho Helen F. , Cooper Peter J. , Murray Lynne
Published: February 2006

Previous studies have suggested that collecting psychiatric data on relatives in family studies by asking probands to provide information on them leads to a bias in estimates of morbidity risk, because probands' accounts are influenced by their own psychiatric histories. We investigated this in a UK sample and found that daughters' anxiety disorder histories did not influence their reports of anxiety disorder in mothers, but their history of mood disorder/alcohol dependence made them more sensitive in predicting mood disorder/alcohol dependence in mothers.
Maternal psychological morbidity and low birth weight in India
Authors: Patel Vikram , Prince Martin
Published: February 2006

Depression following childbirth is associated with poor child growth in developing countries. We describe the association between psychological morbidity during pregnancy and low birth weight (<2.5 kg). A cohort of 270 mothers was recruited from a district hospital in Goa, India; all mothers were interviewed with a screening questionnaire for psychological morbidity. Babies of 250 mothers were reviewed at birth to measure their weight. Excluding 5 premature babies, we found that maternal psychological morbidity was independently associated with low birth weight (odds ratio 1.44, 95% CI 1.00–2.07). We conclude that maternal psychological morbidity has an adverse impact on foetal growth.
Stressful life events, 5-HTT genotype and risk of depression
Authors: Zammit Stanley , Owen Michael J.
Published: February 2006

Studies of how genetic and environmental exposures interact may be essential for understanding the aetiology of complex psychiatric disorders. In this issue of the Journal an Australian study reports evidence of such an interaction on risk of depression. We discuss findings in this field in the context of the limitations inherent in studies of gene–environment interactions.
Service innovations: developing a specialised (tertiary) service for the treatment of affective disorders
Authors: Ker Suzy , Anderson Ian
Published: February 2006

Although the majority of people with mental health problems have their treatment needs met within local services, the Department of Health's Specialised Service National Definition Set (Department of Health, 2002) outlines areas that are thought to require specialised services. Complex and/or treatment-resistant disorders (including severe and/or complex affective disorders) are one of ten mental health areas identified.
Art therapy: a senior house officer's perspective
Authors: Nearney Hannah
Published: February 2006

Francis Dixon Lodge is a therapeutic community in Leicester with a capacity for up to 15 residents. The Lodge also runs a day and out-patient service. The residential programme runs from Monday to Friday (with residents returning home at weekends), and comprises twice daily community meetings, twice weekly small group psychotherapy sessions, a once weekly art therapy group and a once weekly care-planning group. There is also structured time for recreational activities, housekeeping tasks and involvement in assessment of referrals. In addition to planned groups, a crisis meeting can be called at any time by any community member who feels they or another member are struggling in some way. This involves calling on the community to think about how to manage the situation, and is the way that therapeutic communities challenge impulsive behaviours. Individuals may not be at a stage where they feel able to manage their feelings at the time and are likely to ‘act out’ in self-destructive ways, but others around them may be able to offer advice and support. With time, it is hoped that they are able to develop more elastic impulse control (Campling, 2001).
Murky waters: the pharmaceutical industry and psychiatrists in developing countries
Authors: Khan Murad Moosa
Published: February 2006

A multinational pharmaceutical company recently launched a drug for dementia in Pakistan and flew about 70 Pakistani doctors to Bangkok, Thailand for a 3-night all-expenses-paid trip (Khan, 2004). Pakistani doctors were part of a larger group that also included doctors from other countries. A conservative estimate of costs for the Pakistani doctors alone is about 7 million Pakistani rupees (Rs) (£70 000, US$120 000).
Assertive outreach: policy and reality
Authors: Schneider Justine , Brandon Toby , Wooff David , Carpenter John , Paxton Roger
Published: February 2006

Aims and Method

This survey set out to profile the case-loads of assertive outreach teams in North East England, to discover whether they were reaching the people for whom they were meant. A survey of case-loads of 29 assertive outreach teams was carried out using the MARC-2, HoNOS and GAS instruments. Findings were compared with earlier surveys of the case-loads of community mental health teams in parts of the same region.

Results

Clients of assertive outreach teams proved to be at the more severe end of the spectrum on almost every measure: 95% were deemed ‘psychotic’ and 30% had three or more admissions in the previous 2 years.

Conclusions

Assertive outreach teams in the North East are reaching the people they are meant to target. The effects of this shift on existing teams remain to be evaluated.
Development of a Specialty‐wide Web‐based Medical Knowledge Assessment Tool for Resident Education
Authors: Beeson Michael S. , Jwayyed Sharhabeel
Published: March 2006

Medical knowledge is one of six core competencies identified by the Accreditation Council for Graduate Medical Education. The authors present a tool for assessment of medical knowledge developed by the Council of Emergency Medicine Residency Directors. This tool is Internet based and consists of more than 50 online tests that emergency medicine residents are able to access. Test results are available to a resident's residency, along with the mean and standard deviation of all takers of that particular test. The result is a collaborative specialty‐wide approach to the common problem of formatting tests to assess medical knowledge. The tool has been widely accepted by both residents and residencies.
Concurrent Cetuximab, Cisplatin, and Concomitant Boost Radiotherapy for Locoregionally Advanced, Squamous Cell Head and Neck Cancer: A Pilot Phase II Study of a New Combined-Modality Paradigm
Authors: Pfister David G. , Su Yungpo Bernard , Kraus Dennis H. , Wolden Suzanne L. , Lis Eric , Aliff Timothy B. , Zahalsky Andrew J. , Lake Simone , Needle Michael N. , Shaha Ashok R. , Shah Jatin P. , Zelefsky Michael J.
Published: February 2006

Purpose

Cetuximab is a chimeric monoclonal antibody that targets the epidermal growth factor receptor. Cetuximab has activity in squamous cell carcinoma and enhances both chemotherapy and radiotherapy. We conducted a pilot phase II study of a new combined-modality paradigm of targeted therapy (cetuximab) with chemoradiotherapy.

Patients and Methods

Eligible patients had stage III or IV, M0, squamous cell head and neck cancer. Treatment included concomitant boost radiotherapy (1.8 Gy/d weeks 1 to 6; boost: 1.6 Gy 4 to 6 hours later weeks 5 to 6; 70 Gy total to gross disease), cisplatin (100 mg/m2 intravenously weeks 1 and 4), and cetuximab (400 mg/m2 intravenously week 1, followed by 250 mg/m2 weeks 2 to 10).

Results

Twenty-two patients were enrolled (median age, 57 years; range, 41 to 72 years; median Karnofsky status, 90%; range, 70% to 90%; oropharynx primary tumor, 59% of patients; T4, 36%; N2/3, 77%; stage IV disease, 86%). One patient did not receive study treatment because of an ineligible diagnosis. The severity of expected, acute toxicities was typical of concurrent cisplatin and radiotherapy alone. Grade 3 or 4 cetuximab-related toxicities included acne-like rash (10%) and hypersensitivity (5%). However, the study was closed for significant adverse events, including two deaths (one pneumonia and one unknown cause), one myocardial infarction, one bacteremia, and one atrial fibrillation. With a median follow-up of 52 months, the 3-year overall survival rate is 76%, the 3-year progression-free survival rate is 56%, and the 3-year locoregional control rate is 71%.

Conclusion

This regimen is not currently recommended outside of the clinical trial setting. Further investigation of its safety profile is needed. However, preliminary efficacy is encouraging, and further development of this targeted combined-modality paradigm is warranted.
Multiagent Concurrent Chemoradiotherapy for Locoregionally Advanced Squamous Cell Head and Neck Cancer: Mature Results From a Single Institution
Authors: Adelstein David J. , Saxton Jerrold P. , Rybicki Lisa A. , Esclamado Ramon M. , Wood Benjamin G. , Strome Marshall , Lavertu Pierre , Lorenz Robert R. , Carroll Marjorie A.
Published: February 2006

Purpose

A retrospective review with long-term follow-up is reported from the Cleveland Clinic Foundation studying radiation and concurrent multiagent chemotherapy in patients with locoregionally advanced squamous cell head and neck cancer.

Patients and Methods

Between 1989 and 2002, 222 patients were treated with 4-day continuous infusions of fluorouracil (1,000 mg/m2/d) and cisplatin (20 mg/m2/d) during weeks 1 and 4 of either once daily or twice daily radiation therapy. Primary site resection was reserved for patients with residual or recurrent primary site disease after chemoradiotherapy. Neck dissection was considered for patients with N2 or greater disease, irrespective of clinical response, and for patients with residual or recurrent neck disease.

Results

With a median follow-up of 73 months, the Kaplan-Meier 5-year projected overall survival rate is 65.7%, freedom from recurrence rate is 74.0%, local control without the need for surgical resection rate is 86.7%, and overall survival rate with organ preservation is 62.2%. Including patients undergoing primary site resection as salvage therapy, the overall local control rate is 92.4%. Regional control rate at 5 years is 92.4%. Among patients with N2-3 disease, regional control was significantly better if a planned neck dissection was performed. Distant control at 5 years was achieved in 85.4% of patients and was significantly worse in patients with hypopharyngeal primary sites and patients with poorly differentiated tumors.

Conclusion

Concurrent multiagent chemoradiotherapy can result in organ preservation and cure in the majority of appropriately selected patients with locoregionally advanced, nonmetastatic, squamous cell head and neck cancer. Distant metastatic disease was the most common cause of treatment failure. Late functional outcomes will require further investigation.
Advanced Breast Cancer Patients' Perceptions of Decision Making for Palliative Chemotherapy
Authors: Grunfeld Elizabeth A. , Maher E. Jane , Browne Susannah , Ward Pippa , Young Teresa , Vivat Bella , Walker Gay , Wilson Cathy , Potts Henry W. , Westcombe Alex M. , Richards Michael A. , Ramirez Amanda J.
Published: February 2006

Purpose

To examine advanced breast cancer patients' perceptions of the key decision-making consultation for palliative chemotherapy.

Patients and Methods

One hundred two women with advanced breast cancer, who were offered palliative chemotherapy, participated in a study-specific semistructured interview examining perceptions of the information they had received and their involvement in the decision-making process. One hundred seventeen interviews included 70 in relation to first-line chemotherapy and 47 in relation to second-line chemotherapy (15 patients were interviewed in relation to both first- and second-line chemotherapy).

Results

Eighty-six percent of patient interviews (n = 101) reported patient satisfaction with the information they received, and 91% (n = 106) reported satisfaction with the decision-making process. Factors most influential in decisions to accept chemotherapy were the possibility of controlling the tumor (45%, n = 53 of patient interviews) and providing hope (33%, n = 28 of patient interviews; 19%, n = 13 being offered first-line chemotherapy v 43%, n = 20 being offered second-line chemotherapy; P = .006). Thirty-eight percent of patient interviews (n = 44) reported the patient as taking an active role in the decision-making process (33%, n = 23 at first-line chemotherapy v 43%, n = 20 at second-line chemotherapy; P = .06).

Conclusion

Women offered second-line chemotherapy were more likely to undergo chemotherapy because of the hope it offers and were more likely to take an active role in that decision compared with women who were offered first-line chemotherapy. Compassionate and honest communication about prognosis and likelihood of benefit from treatment may help to close the gap between hope and expectation and enable patients to make fully informed decisions about palliative chemotherapy.
Hospice Referral Practices for Children With Cancer: A Survey of Pediatric Oncologists
Authors: Fowler Kimberly , Poehling Katherine , Billheimer Dean , Hamilton Rodney , Wu Huiyun , Mulder John , Frangoul Haydar
Published: February 2006

Purpose

To examine hospice referral patterns among pediatric oncologists and identify barriers to referral.

Methods

A self-administered survey was sent to 1,200 pediatric oncologists who are members of Children's Oncology Group. Two electronic mail messages followed by traditional mail surveys were sent to eligible physicians. Pediatricians and pediatric oncologists developed, pretested, and modified the survey for item clarification.

Results

Of 944 eligible pediatric oncologists surveyed, 632 replied, yielding a response rate of 67%. Most respondents reported having access to palliative care programs (65%) and hospice services (85%), but few (27%) had access to inpatient hospice services. More respondents reported feeling comfortable managing end-of-life pain than psychological issues (86% v 67%, respectively). Many pediatric oncologists (62%) reported that half or more of their patients died in the hospital. In multivariate analysis, physicians with access to hospice that accepts patients receiving chemotherapy had more patients die at home than in hospital compared with physicians without access to such services (P = .007). The probability of hospice referral was positively associated with the presence of a hospice facility (P < .001) and with a larger size oncology group (P = .024). Only 2.5% of respondents referred patients at the time of relapse. Continued therapy was cited as the most common reason for not making a referral, and was significantly higher when hospice did not admit children receiving chemotherapy (P = .002).

Conclusion

Hospice referral for children with cancer is usually made late in the course of their disease and might improve if hospice admits patients who are actively receiving chemotherapy.
Prognostic Value of Pathologic Complete Response After Primary Chemotherapy in Relation to Hormone Receptor Status and Other Factors
Authors: Guarneri Valentina , Broglio Kristine , Kau Shu-Wan , Cristofanilli Massimo , Buzdar Aman U. , Valero Vicente , Buchholz Thomas , Meric Funda , Middleton Lavinia , Hortobagyi Gabriel N. , Gonzalez-Angulo Ana M.
Published: February 2006

Purpose

To evaluate whether hormonal receptor (HR) status can influence the prognostic significance of pathologic complete response (pCR).

Patients and Methods

This retrospective analysis included 1,731 patients with stage I to III noninflammatory breast cancer treated between 1988 and 2005 with primary chemotherapy (PC). Ninety-one percent of patients received anthracycline-based PC, and 66% received additional taxane therapy. pCR was defined as no evidence of invasive tumor in the breast and axillary lymph nodes.

Results

Median age was 49 years (range, 19 to 83 years). Sixty-seven percent of patients (n = 1,163) had HR-positive tumors. A pCR was observed in 225 (13%) of 1,731 patients; pCR rates were 24% in HR-negative tumors and 8% in HR-positive tumors (P < .001). A significant survival benefit for patients who achieved pCR compared with no pCR was observed regardless of HR status. In the HR-positive group, 5-year overall survival (OS) rates were 96.4% v 84.5% (P = .04) and 5-year progression-free survival (PFS) rates were 91.1% v 65.3% (P < .0001) for patients with and without pCR, respectively. For the HR-negative group, 5-year OS rates were 83.9% v 67.4% (P = .003) and 5-year PFS rates were 83.4% v 50.0% (P < .0001) for patients with and without pCR, respectively. After adjustment for adjuvant hormonal treatment, HR status, clinical stage, and nuclear grade, patients who achieved a pCR had 0.36 times the risk of death.

Conclusion

pCR is associated with better outcome regardless of HR status in breast cancer patients who receive PC.
Time Between the First Day of Chemotherapy and the Last Day of Chest Radiation Is the Most Important Predictor of Survival in Limited-Disease Small-Cell Lung Cancer
Authors: De Ruysscher Dirk , Pijls-Johannesma Madelon , Bentzen Søren M. , Minken André , Wanders Rinus , Lutgens Ludy , Hochstenbag Monique , Boersma Liesbeth , Wouters Bradly , Lammering Guido , Vansteenkiste Johan , Lambin Philippe
Published: February 2006

Purpose

To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC).

Methods

A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed.

Results

The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% ± 0.18% (95% CI).

Conclusion

A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.
Quality of Randomized Controlled Trials Reporting in the Primary Treatment of Brain Tumors
Authors: Lai Rose , Chu Rong , Fraumeni Michael , Thabane Lehana
Published: February 2006

Purpose

To assess the reporting quality of randomized controlled trials (RCTs) in the primary treatment of brain tumors and to identify significant predictors of quality.

Patients and Methods

Two investigators searched MEDLINE, EMBASE, and bibliographies of retrieved articles for RCTs in the primary treatment of brain tumors published between January 1990 and December 2004. We assessed the quality of overall reporting and key methodologic factors reporting (allocation concealment, blinding, and intention to treat [ITT]). Two investigators also rated articles independently using items from the revised Consolidated Standards of Reporting Trials statement. A generalized estimated equation was used to generate regression models that identified significant factors associated with quality of reporting.

Results

We retrieved 74 relevant RCTs that randomly assigned 14,498 brain tumor patients. The quality of overall reporting has improved during the last 15 years, but eight of the 15 methodologic items were reported in less than 50% of trials. In the appraisal of the reporting quality of key methodologies, allocation concealment, blinding, and adherence to the ITT principle were reported in less than 30% of articles. Multivariable regression models revealed that an impact factor more than 1.66, publication after 1995, and sample size more than 280 were significant factors associated with better overall reporting, whereas complete industrial funding, impact factors more than 2.64, and positive primary outcomes were predictors of higher ratings of the three most important methodologic qualities.

Conclusion

Despite improvement in general reporting quality, key methodologies that safeguard against biases may still benefit from better description. Significant factors associated with better reporting may act as surrogates for other characteristics.