[Interhospital transport of patients with ARDS]. / Interhospitaltransport von Patienten mit ARDS.

In patients with severely compromised gas exchange, interhospital transportation is frequently necessary due to the need to provide access to specialized care. Risks are inherent during transport, so the anticipated benefits of transportation must be weighed against the possible negative outcome during the transport. The use of specialized teams during transportation can help to reduce adverse events. Diligent planning of the transportation, monitoring and medical staff during transport can decrease adverse events and reduce risks. This article defines the group of patients that may benefit from referral. This article discusses the risks associated with the transportation of patients with severely impaired gas exchange and the risks related to different means of transportation. The decisions required before transportation are described as well as the practical approach starting at the transferring hospital until arrival at the admitting hospital.

[Prone positioning of patients during venovenous extracorporeal membrane oxygenation is safe and feasible]. / Bauchlagerung von Patienten an der venovenösen ECMO ist möglich und sicher.

BACKGROUND: Prone positioning of patients with acute respiratory distress syndrome (ARDS) has been shown to significantly improve survival rates. Prone positioning reduces collapse of dorsal lung segments with subsequent reduction of alveolar overdistension of ventral lung segments, optimizes lung recruitment and enhances drainage. Patients with ARDS treated by extracorporeal membrane oxygenation (ECMO) can also benefit from prone positioning; however, the procedure is associated with a possible higher risk of serious adverse events. OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of prone positioning for patients with severe ARDS during ECMO therapy. MATERIAL AND METHODS: This study involved a retrospective analysis of all patients placed in a prone position while being treated by venovenous ECMO (vvECMO) for severe hypoxemia in ARDS as bridge to recovery in the interdisciplinary intensive care unit at the University Hospital Leipzig between January 2009 and August 2013. Baseline data, hospital mortality and serious adverse events were documented. Serious adverse events were defined as dislocation or obstruction of endotracheal tube or tracheal cannula, ECMO cannulas and cardiac arrest. Prone positioning was carried out by at least one doctor and three nurses according to a standardized protocol. Results are given as the median (1st and 3rd quartiles). RESULTS: A total of 26 patients were treated with vvECMO as bridge to recovery due to severe ARDS. Causes for ARDS were pneumonia (n = 20) and aspiration (n = 2) and four patients had different rare causes of ARDS. The median time on ECMO was 8 days (6;11) and during this period 134 turning events were documented. Patients were proned for a median of 5 (3;7) periods with a median duration of 12 h (8;12). No serious adverse events were recorded. The hospital mortality was 42% and mortality during the ECMO procedure was 35%. CONCLUSION: Prone positioning significantly reduces the mortality of patients with severe ARDS. In this series of 26 patients with severe ARDS during ECMO therapy no serious adverse events were found during the use of prone positioning.

Efficacy of disintegrating aspirin in two different models for acute mild-to-moderate pain: sore throat pain and dental pain.

A recently developed fast-release aspirin tablet formulation has been evaluated in two different pain models. The dental impaction pain model and the sore throat pain model are widely used for assessing analgesia, including acute mild-to-moderate pain. Both studies were double-blind, randomized, parallel group and compared a single dose of 1000 mg aspirin with 1000 mg paracetamol and with placebo and investigated the onset and overall time course of pain relief. Speed of onset was measured by the double-stopwatch method for time to meaningful pain relief and time to first perceptible pain relief. Pain intensity and pain relief were rated subjectively over a 6-h (dental pain) and 2-h (sore throat pain) time period. In both models fast-release aspirin and commercial paracetamol were statistically significantly different from placebo for onset of action, summed pain intensity differences and total pain relief. Meaningful pain relief was achieved within a median of 42.3 and 42.9 min for aspirin and paracetamol, respectively, in the dental pain model. The corresponding numbers in sore throat pain were 48.0 and 40.4 min. All treatments in both studies were safe and well tolerated. No serious adverse events were reported and no subject was discontinued due to an adverse event. Overall the two studies clearly demonstrated efficacy over placebo in the two pain models and a comparable efficacy and safety profile between aspirin and an equivalent dose of paracetamol under the conditions of acute dental pain and acute sore throat pain. Trial registration These trials were registered with ClinicalTrials.gov, registration number: NCT01420094, registration date: July 27, 2011 and registration number: NCT01453400, registration date: October 13, 2011.

Obesity lowers the threshold of allergic sensitization and augments airway eosinophilia in a mouse model of asthma.

BACKGROUND: Clinical and epidemiological studies show a close association between obesity and the risk of asthma development. The underlying cause-effect relationship between metabolism, innate and adaptive immunity, and inflammation remains to be elucidated. METHODS: We developed an animal model to study the interaction between metabolic abnormalities and experimentally induced asthma. Obesity-susceptible AKR mice were fed with high-fat diet (HFD) or normal low-fat diet (LFD) and subjected to a protocol of ovalbumin (OVA) sensitization and airway allergen challenges followed by assessment of inflammation and lung function. RESULTS: AKR mice developed obesity and a prestage of metabolic syndrome following HFD. This phenotype was associated with an increase in proinflammatory macrophages (CD11b+/CD11c+) together with higher serum levels of interleukin 6. Obese mice showed increased susceptibility to allergic sensitization as compared to LFD animals. Anti-ovalbumin IgE antibody titers correlated positively and anti-OVA IgG2a antibodies titers correlated negatively with body weight. Airway eosinophilia showed a positive correlation with body weight, whereas mucus production did not change with obesity. CONCLUSIONS: This obesity model demonstrates that HFD-induced obesity lowers the sensitization threshold in a model of asthma. This finding helps to understand why, particularly during childhood, obesity is a risk factor for the development of allergic asthma.

Evaluation of onset of pain relief from micronized aspirin in a dental pain model.

A new formulation of a micronized acetylsalicylic acid swallowable tablet with an effervescent component (FR-aspirin) was evaluated in two independent studies using the dental impaction pain model. These clinical studies were performed to confirm the results of preclinical dissolution studies and human pharmacokinetic studies, which indicated an improved onset of analgesia without compromising duration of effect or safety. Study 1 evaluated a 650-mg dose of aspirin and Study 2 evaluated a 1,000-mg dose of aspirin. Both studies were double-blinded, parallel group and compared to regular aspirin (R-aspirin) and placebo. Speed of onset was measured by the double stopwatch method for time to both first perceptible relief and meaningful relief. In both studies, the FR-aspirin was significantly faster (p<0.038-0.001) than both R-aspirin and placebo for both onset measures. There were no significant differences between FR-aspirin and R-aspirin for peak or total effects and both treatments were significantly better than placebo. For first perceptible relief, FR-aspirin onset was 19.8 and 16.3 min for 650 mg and 1,000 mg, respectively, compared to 23.7 and 20.0 for R-aspirin. For meaningful relief, FR-aspirin onset was 48.9 and 49.4 min for 650 mg and 1,000 mg, respectively, compared to 119.2 and 99.2 for R-aspirin. These efficacy studies clearly demonstrate that the onset of analgesic efficacy is dramatically improved by adding an effervescent component and micronized active ingredient to the swallowable tablet aspirin formulation. The enhanced onset did not adversely impact either the peak effect or duration of effect or tolerability compared to regular aspirin.

Dissolution and pharmacokinetics of a novel micronized aspirin formulation.

Aspirin (acetylsalicylic acid, ASA) has been used as an analgesic, antipyretic and antiinflammatory drug for many years. A new 500 mg aspirin tablet formulation containing micronized active ingredient and an effervescent component has been developed for potential improvement in the onset of action for acute pain treatment. This paper describes the dissolution and the pharmacokinetics of the new formulation in comparison with regular aspirin tablets, aspirin granules and aspirin effervescent tablets. Micronized aspirin tablets dissolve significantly faster over a pH range from 1.2 to 6.8 compared to regular 500 mg aspirin tablets. Plasma concentration time curve comparison to regular 500 mg aspirin tablets showed a substantial improvement in the time to maximum plasma concentrations (T(max)) (ASA 17.5 min vs. 45 min) and an increase in maximum plasma concentration (C(max)) (ASA 13.8 µg/ml vs. 4.4 µg/ml) while the overall extent of exposure (AUC) remains almost unchanged. The data suggest a potential improvement for onset of action in treating acute pain with the new micronized aspirin formulation.

Gastrointestinal tolerability of aspirin and the choice of over-the-counter analgesia for short-lasting acute pain.

RATIONALE: For the management of common disorders producing short-lasting pain, there is very good evidence of the efficacy of aspirin. Yet paracetamol is often preferred, despite that evidence of its efficacy is much less sound. The reason for this appears to be a concern over gastrointestinal (GI) toxicity. If this concern is misplaced, so may be the preference for paracetamol, with the consequence of widespread sub-optimal treatment. Our purpose in this analysis of pooled individual patient data from clinical studies of aspirin is to adduce the evidence that will show whether or not this is so, for the benefit of consumers and health-care professionals who advise them. METHODS: The frequencies of all and GI adverse events (AEs) and adverse drug reactions (ADRs) were calculated from the pooled individual patient data of nine similar randomized, double-blind, placebo controlled clinical trials of single-doses of aspirin 1000 mg in the treatment of acute migraine attacks, episodic tension-type headache and dental pain. Absolute differences between active and placebo AE and ADR rates, and numbers-needed-to-harm (NNH), were calculated. RESULTS: Of 2852 patients included in the analysis, 1581 were treated with aspirin and 1271 with placebo. Reported AE rates were 14.9% and 11.1% amongst patients allocated to aspirin and placebo respectively (NNH: 26), with the GI system most frequently affected (aspirin: 5.9%; placebo: 3.5%; NNH: 42). Reported ADR rates were much lower (aspirin: 6.3%; placebo: 3.9%; NNH: 42), especially for the GI system (aspirin: 3.1%; placebo: 2.0%; NNH: 91). Most of the AEs and ADRs were mild or moderate, and none was serious. CONCLUSIONS: The GI ADR differences between aspirin and placebo are not great enough to support decision choices for short-lasting acute pain based on tolerability: these are better based on efficacy.

Retinal pigment epithelial tears after single administration of intravitreal bevacizumab for neovascular age-related macular degeneration.

PURPOSE: To analyse retinal pigment epithelial (RPE) tears following single administration of intravitreal bevacizumab for neovascular age-related macular degeneration (AMD) during early follow-up. METHODS: Interventional, retrospective, non-comparative case series included 397 patients (409 eyes) of the 746 consecutive patients that met the eligibility criteria. Standardized visual acuity testing, fluorescein angiography, and optical coherence tomography were performed. Data collected included status of the fellow eye, previous treatment, subtypes of choroidal neovascularization (CNV), size and composition of the lesion. Multiple linear regression modelling was used to explore the effect of baseline parameters on the RPE tears. Primary end point was occurrence of RPE tears within 6 weeks after therapy. RESULTS: Fifteen of the 409 eyes (3.6%) developed RPE tear (95% confidence interval: 2.2-6.0, odds ratio: 26.3). The statistical modelling showed significant association between RPE tear and occult without classic CNV/predominantly haemorrhage vspredominantly/minimal classic CNV (P=0.019), as well as medium or large (>4 disc area) vssmall size of the total lesion (P=0.038). Previous treatment and status of the fellow eye did not statistically influence the risk of RPE tears. CONCLUSIONS: An RPE tear can develop in up to 3.6% of eyes with neovascular AMD following single administration of intravitreal bevacizumab in a short-term follow-up. Medium and large lesion size and occult without classic and predominantly haemorrhagic subtype of CNV were important predictive factors. Preoperative assessment of the lesion characteristics may help in identifying the risk of individual patients with neovascular AMD before intravitreal bevacizumab treatment.

Can the risk of retinal pigment epithelium tears after bevacizumab treatment be predicted? An optical coherence tomography study.

BACKGROUND: Retinal pigment epithelium (RPE) tears after bevacizumab treatment for neovascular age-related macular degeneration accompanied by a pigment epithelial detachment (PED) might be caused by stretching forces on the already weakened RPE. The purpose of this study was to evaluate whether simple measurements of optical coherence tomography (OCT) can predict the individual risk of an RPE tear in preoperative candidates. METHODS: A retrospective chart review study of 393 consecutive patients with neovascular age-related macular degeneration evaluated OCT images (Stratus-OCT Zeiss, Jena, Germany). The height of the PED, the central retinal thickness, and the maximum retinal thickness were determined by two independent observers and retrospectively analysed. RESULTS: Fifteen patients with an RPE tear had a significant higher PED than the remaining study population. In contrast, no correlation was seen with the central retinal thickness. In a linear regression model, the probability of an RPE tear exponentially increased in dependence of the extent of PED. CONCLUSION: The risk of an RPE tear can be estimated by simple measurement of the height of the PED on OCT.

Full macular translocation following photodynamic therapy in neovascular age-related macular degeneration.

PURPOSE: To report the long-term functional and anatomical outcome of full macular translocation (FMT) in eyes with neovascular age-related macular degeneration (AMD) following photodynamic therapy (PDT). METHODS: Twelve eyes of 12 consecutive patients with neovascular AMD who were PDT-nonresponders and underwent FMT were analysed. Best-corrected visual acuity (BCVA) measurement, fundus photography, and fluorescein angiography at baseline and at follow-up examinations in 3 months intervals were performed. Primary end point was change of BCVA from baseline to last visit. RESULTS: Totally 12 eyes of 12 patients were analysed. Mean time interval between the last PDT and FMT was 3.7 months (range 1-10 months). Mean follow-up after FMT was 25.6 months. BCVA ranged at baseline from 20/1000 to 20/80 (mean 20/230). At the last visit, mean BCVA was by 20/185. BCVA improved in 50% (6/12) of eyes by more than 1 line. Twenty five per cent (3/12) of eyes had final BCVA within +/-1 line from baseline. In 25% (3/12) of eyes the BCVA decreased by more than 1 line. One eye had recurrent CNV. In four eyes a cystoid macular oedema developed. No retinal detachment or disturbing diplopia was noted. CONCLUSIONS: In the present study, FMT in PDT-nonresponders stabilised or improved visual acuity in the majority of the eyes in a mean follow-up period of nearly 2 years. FMT can be considered as a therapeutical option in eyes who are nonresponders to the PDT in neovascular AMD.

Efficacy and safety of 1,000 mg effervescent aspirin: individual patient data meta-analysis of three trials in migraine headache and migraine accompanying symptoms.

Migraine is often associated with health consequences including impaired quality of life, and the cost of treating migraine headaches places a significant financial burden on patients who suffer from migraines. Nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans are commonly used for the treatment of acute migraine attacks. Aspirin is widely accepted as a treatment option for migraine pain relief and could provide an alternative not only for treatment of moderate migraine attacks, but also for severe migraine attacks. The efficacy and safety of 1,000 mg effervescent aspirin (eASA) was evaluated in comparison to 50 mg sumatriptan and placebo in an individual patient data meta-analysis of three randomized, placebo-controlled, single- dose migraine trials. Pain-relief at 2 h, pain-free at 2 h and sustained pain-free up to 24 h were calculated. For eASA, the response rates were 51.5 % (95 % CI: 46.6-56.5 %), 27.1 % (95 % CI: 22.6-31.4 %), and 23.5 % (95 % CI: 19.3-27.7 %). For sumatriptan, the response rates were 46.6 % (95% CI: 40.0-53.2 %), 29% (95 % CI: 23.0-34.9 %), and 22.2 % (95 % CI: 16.7-27.6 %). The corresponding rates for placebo were 33.9 % (95% CI: 29.1-38.6 %), 15.1 % (95 % CI: 11.5-18.7 %), and 14.6 % (95 % CI: 11.0-18.1 %). The treatment effect of eASA and sumatriptan were significantly different from placebo (p < 0.001), but differences between eASA and sumatriptan were not significant. The remission of accompanying symptoms and the subgroup analyses of patients with moderate or severe migraine pain at baseline revealed no significant differences between eASA and sumatriptan. Safety was evaluated based on the frequency of reported adverse events, and treatment with eASA was associated with lower incidence of adverse events than was with sumatriptan. This individual patient data meta-analysis provided evidence that eASA 1,000 mg is as effective as sumatriptan 50mg for the treatment of acute migraine attacks and has a better side effect profile. This is also true for patients with moderate as well as severe headache at baseline. Patients therefore should be advised to use eASA first for migraine attacks and use a triptan in case of no response.

Insulin-like growth factor-1 receptor immunoreactive cells are selectively maintained in the paraventricular hypothalamus of calorically restricted mice.

The mammalian lifespan is dramatically extended by both caloric restriction (CR) and insulin-like growth factor-1 (IGF-1) suppression. Both interventions involve neuroendocrine alterations directed by the hypothalamus. Yet, it remains unclear whether CR exerts its affects by altering central IGF-1 sensitivity. With this question in mind, we investigated the influence of CR and normal aging on hypothalamic IGF-1 sensitivity, by measuring the changes in IGF-1 receptor (IGF-1R) populations. Taking IGF-1 receptor (IGF-1R) immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the paraventricular nucleus (PVN) of Young-ad libitum fed (Young-Al, 6 weeks old), Old-ad libitum fed (Old-Al, 22 months old), and old calorically restricted (Old-CR, 22 months old) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each cross-section of PVN hypothalamus. Ad libitum fed mice show a 37% reduction in IGF-1R immunoreactive cells and a 12% reduction in the total cell population of the PVN with aging. In comparison, caloric-restricted mice show a 33% reduction in IGF-1R immunoreactive cells and a notable 24% decrease in the total cell population with aging. This selective maintenance of IGF-1R expressing cells coupled with the simultaneous loss of non-immunoreactive cells, results in a higher percentage of IGF-1R immunoreactive cells in the PVNs of CR mice. Thus, the decline in the percentage of IGF-1 sensitive cells in the PVN with age is attenuated by CR.

Age-dependent loss of insulin-like growth factor-1 receptor immunoreactive cells in the supraoptic hypothalamus is reduced in calorically restricted mice.

Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. Of the hypothalamic nuclei that express the IGF-1 receptor (IGF-1R), the cells of the supraoptic nucleus (SON) display some of the most robust IGF-1R expression. Taking IGF-1R immunoreactivity as an index of sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive cells in the SON of young-ad-libitum fed (young-Al, 6 weeks), old-ad-libitum fed (Old-Al, 22 months), and old-calorie-restricted (Old-CR, 22 months) female B6D2F1 mice. An automated imaging microscopy system (AIMS) was used to generate cell counts for each section of supraoptic hypothalamus. Results show that while the total number of cells in the SON of ad-libitum fed mice does not change significantly with aging, a significant reduction in IGF-1R immunoreactive cells does occur in ad-libitum fed mice with aging. In contrast to this, calorie restricted mice show both a decline in the total number of cells and IGF-1R immunoreactive cells in the SON with age, but with the decrease in the latter being notably attenuated when compared to the degree of loss seen in ad-libitum fed mice. Thus, while CR induces greater loss in the total number of cells in the SON with age, it reduces the degree of age-dependent loss seen in IGF-1R expressing cells. As a result, when compared to Old-AL mice, the SON of Old-CR mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging.

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks.

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.

Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in treating associated migraine symptoms.

Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering capacity has been developed. In this double-blind, 3-arm, multicenter, parallel-group study, 433 patients were treated either with 1,000 mg effervescent ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the percentage of patients with complete remission of the 3 accompanying symptoms nausea, photophobia and phonophobia within 2 h after intake of the study drug. 43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan and 30.9% of patients treated with placebo showed complete remission of all 3 accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active treatments were superior to placebo regarding the individual symptoms photophobia and phonophobia, but not for nausea. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (secondary objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of patients treated with ASA, sumatriptan or placebo were pain free at 2 h. Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients treated with placebo, ASA or sumatriptan. The study showed that administration of effervescent ASA leads to remission of the migraine symptoms nausea, photophobia and phonophobia, reduces migraine headache and is comparable to sumatriptan.

Clinicopathological findings of choroidal neovascularisation following verteporfin photodynamic therapy.

AIMS: To report the clinicopathologic findings of surgically excised choroidal neovascularisation (CNV) three days after verteporfin photodynamic therapy (PDT). METHODS: In three patients (three eyes) with age related macular degeneration, the CNV was surgically removed three days after PDT. The CNV specimens were examined by light microscopy. RESULTS: The patients had subfoveal classic CNV. Fluorescein angiography revealed non-perfusion of the CNV after PDT and before surgery in all eyes. The light microscopy of the CNV membranes showed swollen and damaged endothelium. Thrombus formation or vascular occlusion in the CNV vessels was not detected. CONCLUSION: PDT did not cause a thrombosis of the vessels within the CNV three days after PDT. Severe endothelial damage of the CNV was observed and is likely a primary effect of PDT. Non-perfusion of the CNV at this stage is possibly secondary to occlusion at a deeper level, namely the underlying feeding choroid.

Serum markers of matrix turnover as predictors for the evolution of colorectal cancer metastasis under chemotherapy.

Connective tissue turnover plays a prominent role in tumour growth and metastasis. We followed serum levels of seven connective tissue parameters in 37 patients with colorectal cancer metastatic to the liver prior to and during chemotherapy. Serum samples with episodes of tumour control (n=112) showed an increase of matrix metalloproteinase-2 (MMP-2) (P

Aspirin in episodic tension-type headache: placebo-controlled dose-ranging comparison with paracetamol.

Most people with episodic tension-type headache (TTH) treat themselves with over-the-counter analgesics. In the absence of clear evidence of dose-related efficacy of the two most commonly used analgesics, aspirin (acetylsalicylic acid) and paracetamol (acetaminophen), this study compared two doses of each with placebo. In a double-blind, double-dummy, randomized parallel-groups comparative trial, 638 consenting subjects aged 16-65 years with episodic TTH (but not migraine) by IHS criteria were recruited from the UK general population by advertisement. They treated one episode of moderate or severe TTH with a single dose of 500 or 1000 mg aspirin, 500 or 1000 mg paracetamol or placebo. The primary objective was to compare aspirin 1000 mg with placebo, and the primary end-point was subjective pain relief (total or worthwhile) 2 h after treatment ('response'). Additionally, pain intensity on a 100-mm visual analogue scale and functional impairment were monitored regularly for 4 h and at 24 h, although rescue medication was allowed after 2 h. The analysis was of the intention-to-treat population of 542 who took treatment (all providing outcome data). Treatment groups were matched at baseline. Aspirin 1000 mg (75.7% response rate; P = 0.0009) and to a lesser extent aspirin 500 mg (70.3%; P = 0.011) and paracetamol 1000 mg (71.2%; P = 0.007), but not paracetamol 500 mg (63.8%; P = 0.104), were statistically more effective than placebo despite a high placebo-response rate (54.5%). Outcome was not affected by headache intensity at baseline. Secondary end-points including functional recovery (by median times of 4.0-13.5 h) were consistent with these findings, although a minority of subjects recorded long-duration functional impairment (37-54 h). Adverse events reported by 13.4-18.9% of subjects were mild or moderate, and transient. No safety concerns arose.

Self-reported postwar injuries among Gulf War veterans.

OBJECTIVE: From September 1995 to May 1996, the authors conducted a telephone survey of Iowa military personnel who had served in the regular military or activated National Guard or Reserve during the Gulf War period. To assess the association between military service in a combat zone and subsequent traumatic injury requiring medical consultation, the authors analyzed veterans' interview responses. METHODS: Using data from the larger survey, the authors compared rates of self-reported postwar injuries requiring medical consultation in a sample of Iowa Gulf War veterans to the rates in a sample of Iowa military personnel who served at the same time, but not in the Persian Gulf. RESULTS: Of 3695 veterans, 605 (16%) reported a traumatic injury in the previous three months requiring medical consultation. Self-reported injuries were associated with service in the Persian Gulf (odds ratio 1.26; 95% confidence interval 1.02, 1.55). CONCLUSION: This finding is consistent with the results of earlier studies of traumatic injury mortality rates among war veterans.