Hot off the presses! Jul 18 Lancet

The Jul 18 issue of the Lancet is now up on Pubget (About Lancet): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

• Embryonic stem cells, Francis Collins, and the NIH
  - Lancet 374(9685):175 (2009)
  
• Phase 0 trials: a platform for drug development?
  - Lancet 374(9685):176 (2009)
  
• Counteracting myths about immigration and health
  - Lancet 374(9685):176 (2009)
  
• Facial transplantation: lessons so far
  - Lancet 374(9685):177-178 (2009)
  
• Treatment of rheumatoid arthritis: we are getting there
  - Lancet 374(9685):178-180 (2009)
  
• Interferon gamma for idiopathic pulmonary fibrosis
  - Lancet 374(9685):180-182 (2009)
  
• Male circumcision and HIV risks and benefits for women
  - Lancet 374(9685):182-184 (2009)
  
• PEPFAR's biggest success is also its largest liability
  - Lancet 374(9685):184-185 (2009)
  
• Antiretroviral roll-out: the problem of second-line therapy
  - Lancet 374(9685):185-186 (2009)
  
• Guatemala's malnutrition crisis
  - Lancet 374(9685):187-189 (2009)
  
• Uganda to reintroduce female condoms
  - Lancet 374(9685):190 (2009)
  
• AIDS treatment in Brazil: success beyond measure?
  - Lancet 374(9685):191-192 (2009)
  
• Exploring epidemics
  - Lancet 374(9685):192 (2009)
  
• Robin Gorna takes the helm at the International AIDS Society
  - Lancet 374(9685):193 (2009)
  
• The patient's view: John Donne and Katharine Anne Porter
  - Lancet 374(9685):194-195 (2009)
  
• Edward Bromfield
  - Lancet 374(9685):196 (2009)
  
• Effect on survival of whole-body CT during trauma resuscitation
  - Lancet 374(9685):197 (2009)
  
• Effect on survival of whole-body CT during trauma resuscitation
  - Lancet 374(9685):197 (2009)
  
• Effect on survival of whole-body CT during trauma resuscitation
  - Lancet 374(9685):197-198 (2009)
  
• Effect on survival of whole-body CT during trauma resuscitation
  - Lancet 374(9685):198 (2009)
  
• Effect on survival of whole-body CT during trauma resuscitation – Authors' reply
  - Lancet 374(9685):198-199 (2009)
  
• Haemodialysis access via tissue-engineered vascular graft
  - Lancet 374(9685):199-200 (2009)
  
• Haemodialysis access via tissue-engineered vascular graft
  - Lancet 374(9685):200 (2009)
  
• Haemodialysis access via tissue-engineered vascular graft
  - Lancet 374(9685):200 (2009)
  
• Haemodialysis access via tissue-engineered vascular graft
  - Lancet 374(9685):200-201 (2009)
  
• Haemodialysis access via tissue-engineered vascular graft – Authors' reply
  - Lancet 374(9685):201 (2009)
  
• The Gates Foundation: looking at the bigger picture
  - Lancet 374(9685):201-202 (2009)
  
• Who should defend us from collective defamation?
  - Lancet 374(9685):202 (2009)
  
• Department of Error
  - Lancet 374(9685):202 (2009)
  
• Near-total human face transplantation for a severely disfigured patient in the USA
  - Lancet 374(9685):203-209 (2009)
  Background Multiple reconstructive procedures are common for the reconstruction of complex facial deformities of skin, soft tissues, bony structures, and functional subunits, such as the nose, lips, and eyelids. However, the results have been unsatisfactory. An innovative approach entailing a single surgical procedure of face allograft transplantation is a viable alternative and gives improved results. Methods On Dec 9, 2008, a 45-year-old woman with a history of severe midface trauma underwent near-total face transplantation in which 80% of her face was replaced with a tailored composite tissue allograft. We addressed issues of immunosuppressive therapy, psychological and ethical outcomes, and re-integration of the patient into society. Findings After the operation, the patient did well physically and psychologically, and tolerated immunosuppression without any major complication. Routine biopsy on day 47 after transplantation showed rejection of graft mucosa; however, a single bolus of corticosteroids reversed rejection. During the first 3 weeks after transplantation, the patient accepted her new face; 6 months after surgery, the functional outcome has been excellent. In contrast to her status before transplantation, the patient can now breathe through her nose, smell, taste, speak intelligibly, eat solid foods, and drink from a cup. Interpretation We show the feasibility of reconstruction of severely disfigured patients in a single surgical procedure using composite face allotransplantation. Therefore, this should be taken in consideration as an early option for severely disfigured patients. Funding None.
• Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor α inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial
  - Lancet 374(9685):210-221 (2009)
  Background Tumour necrosis factor α (TNFα) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFα inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFα inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNFα inhibitors. Methods 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were randomly allocated by interactive voice response system, stratified by study site and methotrexate use, to receive subcutaneous injections of placebo (n=155), 50 mg golimumab (n=153), or 100 mg golimumab (n=153) every 4 weeks between Feb 21, 2006, and Sept 26, 2007. Allocation was double-blind. Eligible patients had been treated with at least one dose of a TNFα inhibitor previously. Patients continued stable doses of methotrexate, sulfasalazine, hydroxychloroquine, oral corticosteroids, and non-steroidal anti-inflammatory drugs. The primary endpoint was achievement at week 14 of 20% or higher improvement in American College of Rheumatology criteria for assessment of rheumatoid arthritis (ACR20). At week 16, patients who had less than 20% improvement in tender and swollen joint counts were given rescue therapy and changed treatment from placebo to 50 mg golimumab, or from 50 mg to 100 mg golimum! ab. Drug efficacy was assessed by intention to treat and safety was assessed according to the study drug given. This study is registered with ClinicalTrials.gov, number NCT00299546. Findings Patients had discontinued previous TNFα inhibitors because of lack of effectiveness (269 [58%] patients) or reasons unrelated to effectiveness (246 [53%] patients), such as intolerance and accessibility issues. Patients had active disease, which was indicated by a median of 14·0 (IQR 9·0–22·0) swollen and 26·0 (16·0–41·0) tender joints for the whole group. 28 (18%) patients on placebo, 54 (35%) patients on 50 mg golimumab (odds ratio 2·5 [95% CI 1·5–4·2], p=0·0006), and 58 (38%) patients on 100 mg golimumab (2·8 [1·6–4·7], p=0·0001) achieved ACR20 at week 14. Two patients were never treated, and 57 patients did not complete the study because of adverse events, unsatisfactory treatment effect, loss to follow-up, death, or other reasons. 155 patients on placebo, 153 on 50 mg golimumab, and 153 on 100 mg golimumab were assessed for drug efficacy. For weeks 1–16, serious adverse events were recorded in 11 (7%) patients on placebo, 8 (5%) on 50 mg golimum! ab, and 4 (3%) on 100 mg golimumab. For weeks 1–24, after some patients were given rescue therapy, serious adverse events were recorded in 15 (10%) patients on placebo, 14 (5%) on 50 mg golimumab, and 8 (4%) on 100 mg golimumab. Interpretation Golimumab reduced the signs and symptoms of rheumatoid arthritis in patients with active disease who had previously received one or more TNFα inhibitors. Funding Centocor Research and Development and Schering-Plough Research Institute.
• Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial
  - Lancet 374(9685):222-228 (2009)
  Background Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function. Methods 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries, the USA, and Canada. Patients were randomly assigned (double-blind) in a 2:1 ratio to receive 200 μg interferon gamma-1b (n=551) or equivalent placebo (n=275) subcutaneously, three times per week. Eligible patients were aged 40–79 years, had been diagnosed in the past 48 months, had a forced vital capacity of 55–90% of the predicted value, and a haemoglobin-corrected carbon monoxide diffusing capacity of 35–90% of the predicted value. The primary endpoint was overall survival time from randomisation measured at the second interim analysis, when the proportion of deaths had reached 75% of those expected by the study conclusion. This study is registered with ClinicalTrials.gov, number NCT00075998. Findings At the second interim analysis, the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo (1·15, 95% CI 0·77–1·71, p=0·497), and indicated that the study should be stopped. After a median duration of 64 weeks (IQR 41–84) on treatment, 80 (15%) patients on interferon gamma-1b and 35 (13%) on placebo had died. Almost all patients reported at least one adverse event, and more patients on interferon gamma-1b group had constitutional signs and symptoms (influenza-like illness, fatigue, fever, and chills) than did those on placebo. Occurrence of serious adverse events (eg, pneumonia, respiratory failure) was similar for both treatment groups. Treatment adherence was good and few patients discontinued treatment prematurely in either group. Interpretation We cannot recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis, which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function. Funding InterMune.
• Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial
  - Lancet 374(9685):229-237 (2009)
  Background Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners. Methods 922 uncircumcised, HIV-infected, asymptomatic men aged 15–49 years with CD4-cell counts 350 cells per μL or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878. Findings The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0·36). Cumulative probabilities of female HIV infection at 24 months were 21·7% (95% CI 12·7–33·4) in the intervention group and 13·4% (6·7–25·8) in the control group (adjusted hazard ratio 1·49, 95% CI 0·62–3·57; p=0·368). Interpretation Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention. Funding Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center.
• Nail-gun narcolepsy
  - Lancet 374(9685):238 (2009)
  
• Bladder cancer
  - Lancet 374(9685):239-249 (2009)
  Bladder cancer is a heterogeneous disease, with 70% of patients presenting with superficial tumours, which tend to recur but are generally not life threatening, and 30% presenting as muscle-invasive disease associated with a high risk of death from distant metastases. The main presenting symptom of all bladder cancers is painless haematuria, and the diagnosis is established by urinary cytology and transurethral tumour resection. Intravesical treatment is used for carcinoma in situ and other high grade non-muscle-invasive tumours. The standard of care for muscle-invasive disease is radical cystoprostatectomy, and several types of urinary diversions are offered to patients, with quality of life as an important consideration. Bladder preservation with transurethral tumour resection, rad iation, and chemotherapy can in some cases be equally curative. Several chemotherapeutic agents have proven to be useful as neoadjuvant or adjuvant treatment and in patients with metastati! c disease. We discuss bladder preserving approaches, combination chemotherapy including new agents, targeted therapies, and advances in molecular biology.
• Non-invasive ventilation in acute respiratory failure
  - Lancet 374(9685):250-259 (2009)
  Non-invasive mechanical ventilation has been increasingly used to avoid or serve as an alternative to intubation. Compared with medical therapy, and in some instances with invasive mechanical ventilation, it improves survival and reduces complications in selected patients with acute respiratory failure. The main indications are exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, pulmonary infiltrates in immunocompromised patients, and weaning of previously intubated stable patients with chronic obstructive pulmonary disease. Furthermore, this technique can be used in postoperative patients or those with neurological diseases, to palliate symptoms in terminally ill patients, or to help with bronchoscopy; however further studies are needed in these situations before it can be regarded as first-line treatment. Non-invasive ventilation implemented as an alternative to intubation should be provided in an intensive care or high-dependency uni! t. When used to prevent intubation in otherwise stable patients it can be safely administered in an adequately staffed and monitored ward.
• AIDS: lessons learnt and myths dispelled
  - Lancet 374(9685):260-263 (2009)
  
• Eradication of insulin resistance
  - Lancet 374(9685):264 (2009)