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Sepsis remains one of the leading causes of mortality in critically ill patients. Increased insight into the complexities of this disease process has resulted in the targeting of various aspects of the inflammatory response as offering potential therapeutic benefits. There have been encouraging results in the past few years. Some of the tested agents have been shown to improve mortality rates in large randomized controlled trials involving patients with severe sepsis. In this article, we discuss the positive and negative results of trials in this field; some of the possible reasons for the negative results are examined, and directions for the future are suggested.

Objectives: (1) To establish risk factors for the development of delirium in an intensive care unit (ICU) and (2) to determine the effect of delirium on morbidity, mortality and length of stay., Design: Prospective study., Setting: Sixteen-bed medical/surgical ICU in a university hospital., Patients: Two hundred and sixteen consecutive patients admitted to the ICU for more than 24 h during 5 months were included in the study., Interventions: Medical history, selected laboratory values, drugs received and factors that may influence patient psychological and emotional well-being were noted. All patients were screened with a delirium scale. A psychiatrist confirmed the diagnosis of delirium. Major complications such as self-extubation and removal of catheters, as well as mortality and length of stay were recorded., Results: Forty patients (19%) developed delirium; of these, one-third were not agitated. In the multivariate analysis hypertension, smoking history, abnormal bilirubin level, epidural use and morphine were statistically significantly associated with delirium. Traditional factors associated with the development of delirium on general ward patients were not significant in our study. Morbidity (self-extubation and removal of catheters), but not mortality, was clearly increased., Conclusion: Predictive risk factors for the development of delirium in studies outside the ICU may not be applicable to critically ill patients. Delirium is associated with increased morbidity. Awareness of patients at risk may lead to better recognition and earlier intervention.

Objective: Delirium in the intensive care unit is poorly defined. Clinical evaluation is difficult in the setting of unstable, often intubated patients. A screening tool may improve the detection of delirium., Method: We created a screening checklist of eight items based on DSM criteria and features of delirium: altered level of consciousness, inattention, disorientation, hallucination or delusion, psychomotor agitation or retardation, inappropriate mood or speech, sleep/wake cycle disturbance, and symptom fluctuation. During 3 months, all patients admitted to a busy medical/surgical intensive care unit were evaluated, and the scale score was compared to a psychiatric evaluation., Results: In 93 patients studied, 15 developed delirium. Fourteen (93%) of them had a score of 4 points or more. This score was also present in 15 (19%) of patients without delirium, 14 of whom had a known psychiatric illness, dementia, a structural neurological abnormality or encephalopathy. A ROC analysis was used to determine the sensitivity and specificity of the screening tool. The area under the ROC curve is 0.9017. Predicted sensitivity is 99% and specificity is 64%., Conclusion: This study suggests that the Intensive Care Delirium Screening Checklist can easily be applied by a clinician or a nurse in a busy critical care setting to screen all patients even when communication is compromised. The tool can be utilized quickly and helps to identify delirious patients. Earlier diagnosis may lead to earlier intervention and better patient care.

Objectives: To determine the aetiology of urethritis in Bangui, Central African Republic., Methods: 410 men presenting with urethral discharge and 100 asymptomatic controls were enrolled. Urethral swabs were obtained and processed by gonococcal culture and polymerase chain reaction for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum., Results: In multivariate analyses, M genitalium and C trachomatis were significantly associated with urethral discharge when comparing cases of non-gonococcal urethritis (NGU) with controls. T vaginalis was also more common in cases than in controls, but this reached statistical significance only among cases in whom N gonorrhoeae was also detected. U urealyticum was not associated with urethritis. The gonococcus was found in 69% of cases of urethral discharge. M genitalium was the predominant pathogen in patients with NGU, being found in 42% (53/127) of such patients while C trachomatis was found in only 17% (22/127). T vaginalis was found in 18% (23/127) of patients with NGU, but also in 15% (43/283) of patients with gonococcal urethritis, and two thirds of patients with T vaginalis also had the gonococcus. Multiple infections were common. M genitalium caused a syndrome similar to chlamydial urethritis, with a less severe inflammation than in gonococcal infection. No behavioural or clinical characteristic could discriminate between the various aetiological agents., Conclusions: M genitalium is more prevalent than C trachomatis and is the most common cause of NGU in BANGUI: It causes a syndrome similar to chlamydial urethritis. T vaginalis is weakly associated with urethritis, and is often found along with other pathogens.

Background: Interventions for upgrading sexually transmitted disease (STD) management in sub-Saharan Africa have focused on the public sector, and to a much lower extent on private medical practitioners and pharmacies. However, in most African cities there is a large informal sector that provides care to many patients with STD symptoms., Goal: To compare the quality of treatments offered to patients with major STD syndromes in the public sector, pharmacies, and the informal sector of the same city., Study Design: Healthcare providers in health centers, pharmacies, private laboratories, and market drug peddlers in Bangui, Central African Republic, were asked to complete a short form for every patient consulting them with genital complaints. The treatments they ordered were evaluated for their potential efficacy against the major etiologic agents of the syndrome for which the patient consulted., Results: The majority of male patients with STDs preferred to seek care in pharmacies and in the informal sector. The STD treatments offered to patients with urethral discharge or genital ulcers in pharmacies and in the informal sector tended to focus on a single etiologic agent. The quality of STD treatments offered by drug peddlers and private laboratories was poor, apart from adequate coverage of syphilis in patients with genital ulcers and of candidiasis in women with vaginal discharge. For instance, 41% and 34% of patients with urethral discharge managed by drug peddlers and private laboratories did not receive a drug active against either Neisseria gonorrhoeae or Chlamydia trachomatis, whereas this proportion was 22% in pharmacies and 14% in health centers. For patients with genital ulcers, the proportion offered a drug active against Haemophilus ducreyi was 2% if seen by drug peddlers, 0% in laboratories, 10% in pharmacies, and 25% in health centers. For each syndrome and each category of provider, between one fourth and two thirds of patients had already received another ineffective treatment elsewhere., Conclusion: National STD and HIV control programs will have to improve STD management in pharmacies and in the informal sector if they are to have any impact on the dynamics of HIV infection in urban centers.

Our insight of the sepsis response has evolved to encompass not only the pro-inflammatory but also an anti-inflammatory reaction following infection. Clinical trials have been designed to target either bacterial products, endotoxin in particular, or mediators involved in the sepsis response, but until recently the majority of them have given unfavorable results. In this article, we provide a scope of clinical trials that have been done in immunomodulation during sepsis whether or not they provide positive results. We will also discuss some of the reasons why those studies have been disappointing. Current and future trials with a better assessment of inflammatory status of patients and better-defined outcomes such as organ dysfunction are now underway.