Management Of Treatment Failure Research Articles

Malaysian joint societies' consensus recommendations on diagnosis and management of disorders of esophagogastric junction outflow.

Disorders of esophagogastric junction (EGJ) outflow, including achalasia and EGJ outflow obstruction, are motility disorders characterized by inadequate relaxation of lower esophageal sphincter with or without impaired esophageal peristalsis. Current guidelines are technical and less practical in the Asia-Pacific region, and there are still massive challenges in timely diagnosis and managing these disorders effectively. Therefore, a Malaysian joint societies' task force has developed a consensus on disorders of EGJ outflow based on the latest evidence, while taking into consideration the practical relevance of local and regional context and resources. Twenty-one statements were established after a series of meetings and extensive review of literatures. The Delphi method was used in the consensus voting process. This consensus focuses on the definition, diagnostic investigations, the aims of treatment outcome, non-surgical or surgical treatment options, management of treatment failure or relapse, and the management of complications. This consensus advocates the use of high-resolution esophageal manometry for diagnosis of disorders of EGJ outflow. Myotomy, via either endoscopy or laparoscopy, is the preferred treatment option, while pneumatic dilatation can serve as a secondary option. Evaluation and management of complications including post-procedural reflux and cancer surveillance are recommended.

Abstract 15982: Management and Follow-Up of Inpatients With Cardiac Implantable Electronic Devices and Bacteremia With and Without Electrophysiology Consultation

Introduction: Transvenous cardiac implantable electronic device (CIED) infection is a significant cause of morbidity and mortality. Expert consensus recommends a multidisciplinary approach to bacteremia in the context of CIED incorporating both infectious disease (ID) and electrophysiology (EP) consultation to balance the risks of infection with those of CIED removal. Hypothesis: Not all patients with CIEDs and bacteremia are evaluated with EP consultation, and this difference is associated with variability in management. Methods: Using the EMR, we retrospectively identified inpatients with a CIED and a positive blood culture across three hospitals: one academic, one specialty and one community. True infection versus contaminant was determined by an EP or ID attending at the time of presentation or adjudicated retrospectively by an EP who performs extractions. We examined the rates of EP consultation based on hospital site, CIED removal and appropriate follow-up in those without CIED removal. Fisher’s exact test was used to compare the rates of follow up. Results: We identified 88 inpatients with a CIED and positive blood culture between January 2020 - February 2023. True bacteremia was adjudicated in 48 patients (55%). Of these patients, 24 were seen by EP (50%), 22 were seen by EP and ID (46%), and 14 were seen by neither (29%). Patients admitted to an academic hospital were more likely to be seen by EP (22/38, 57%) than those admitted to a specialty or community hospital (2/10, 20%). CIED removal was performed in 15 of 24 patients seen by EP (63%). Patients seen by EP were significantly more likely to have documented plans, repeat blood cultures after antibiotic completion, and appropriate follow up than those not seen by EP (24/24 100% vs. 3/24, 8%, p<0.001). Conclusion: Even at a high-volume extraction center, EP consultation for patients with true bacteremia in the context of CIED only occurred 50% of the time. Patients admitted to an academic hospital were more likely to be seen by EP than at a community or subspecialty hospital. EP consultation is important for all bacteremic patients with CIEDs, not only to recommend extraction if appropriate, but also to ensure timely follow-up and management of treatment failure, consistent with expert consensus.

Implications of using home urine pregnancy tests versus facility-based tests for assessment of outcome following medication abortion provided via telemedicine

ObjectivesTo assess whether planning high-sensitivity urine pregnancy tests (HSPT) rather than facility-based tests for medication abortion follow-up may increase risk of unplanned clinical visits or procedural completion of the abortion. Study designWe used data from the TelAbortion Project, a 5-year study assessing the safety and feasibility of providing mifepristone and misoprostol by telemedicine and mail in the United States. We categorized participants by whether the pretreatment follow-up plan included HSPT at home 3–5 weeks after treatment or facility-based tests (ultrasound or serum human chorionic gonadotropin) within 2 weeks after treatment. We used multivariable logistic regression to compare likelihood of post-treatment unplanned, abortion-related clinical visits and procedural intervention in these groups. ResultsOf 1324 patients who planned HSPT follow-up and 576 who planned facility-based tests, 85% and 83%, respectively, provided outcome information. Post-treatment clinical visits were less frequent in the HSPT group (19%) than in the facility-based test group (79%); most of the latter were to obtain the planned test. However, unplanned, abortion-related visits were significantly more common in the HSPT group (adjusted risk difference: 6.5%; p < 0.01). The likelihood of procedural completion did not differ by group. Planned follow-up test was not associated with delay in procedural completion or detection of ongoing pregnancy. ConclusionsFollow-up of medication abortion with home HSPT was associated with fewer post-treatment clinical visits, modestly more unplanned, abortion-related clinical visits, and no increase in the risk of procedural interventions or delayed identification or management of treatment failures. This option is an appropriate follow-up approach after medication abortion. ImplicationsUse of home high-sensitivity pregnancy tests rather than facility-based tests for outcome assessment after medication abortion is associated with a modest increase in unplanned clinical visits but does not lead to an increase in procedural interventions or delays identification and management of treatment failure.

Urgent need to improve programmatic management of patients with HIV failing first-line antiretroviral therapy.

Delayed identification and response to virologic failure in case of first-line antiretroviral therapy (ART) in resource-limited settings is a threat to the health of HIV-infected patients. There is a need for the implementation of an effective, standardized response pathway in the public sector. We evaluated published cohorts describing virologic failure on first-line ART. We focused on gaps in the detection and management of treatment failure, and posited ways to close these gaps, keeping in mind scalability and standardization. Specific shortcomings repeatedly recorded included early loss to follow-up (>20%) after recognized first-line ART virologic failure; frequent delays in confirmatory viral load testing; and excessive time between the confirmation of first-line ART failure and initiation of second-line ART, which exceeded 1 year in some cases. Strategies emphasizing patient tracing, resistance testing, drug concentration monitoring, adherence interventions, and streamlined response pathways for those failing therapy are further discussed. Comprehensive, evidence-based, clinical operational plans must be devised based on findings from existing research and further tested through implementation science research. Until this standard of evidence is available and implemented, high rates of losses from delays in appropriate switch to second-line ART will remain unacceptably common and a threat to the success of global HIV treatment programs.

Implementierung der Behandlung durch enzymatisches Debridement bei Verbrennungen – Ergebnisse eines interprofessionellen, deutschsprachigen Expertenworkshops

Since its introduction in 2013 Bromelain-based Enzymatic Debridement (ED) is increasingly used in burn centers. Published evidence shows its efficiency in eschar removal as well as a superiority in blood loss and necessity of further surgical procedures compared to standard-of-care. While the procedure is safe and shows reliable results in experienced hands, some practical and logistical issues must be challenged that are not described sufficiently in available literature. A multi-professional panel, consisting of experienced users of ED from German-speaking burn units has been invited to an expert workshop. Topics concerning indication, definition of treatment pathways, practical issues, post-treatment and handling of complications have been coordinated in advance to allow discussion during the workshop. To each topic practical recommendations were developed and consented. Summarizing key messages have been additionally highlighted. They aim on helping to achieve optimal results after establishing the technique by new users as well as optimizing results by experienced users. Amongst others, the resulting recommendations deal with indications for ED beyond the classic domain, different treatment pathways depending on burn depth and primary result after ED with adapted post-treatment, management of treatment failure and implementation of infrastructural conditions. While efficiency of ED as well as superiority in some aspects of treatment of burn wounds could be shown in available literature, user-oriented recommendations for practical implementation are scarce. Although the recommendations and experts opinions published here are only partly evidenced based, they are still based on the pooled experienced of the panelists that easily outnumbers the cases published in literature so far and allow valuable support for a successful implementation of the technique.

Induced-membrane treatment of refractory humeral non-union with or without bone defect

IntroductionTreatment of humeral non-union with or without bone defect is complex, with non-negligible rates of complication and failure. Few reports focused on management of treatment failure. ObjectiveThe study hypothesis was that the induced-membrane technique associated in a 2-stage strategy to internal fixation provides systematic bone healing in refractory humeral non-union. Material and methodsThe study included 15 patients, with a median age of 46.6 years, with humeral non-union of a mean 24 months’ progression and mean history of 3 attempted revision surgeries. Seven patients showed bone defect, exceeding 5cm in 2 cases. Six had history of radial palsy. ResultsConsolidation was achieved in all cases, at a mean 4.6 months. Ten patients underwent radial nerve transposition, 6 of whom had shown radial motor nerve palsy; all recovered within 2 to 5 months. There was 1 case of superficial infection, and 1 of seroma. DiscussionThe induced-membrane technique ensures bone healing due to the biological properties of the membrane; the main drawback is the need for 2-stage surgery. When bone defect exceeds 5cm, a multi-perforated fibula segment can be placed inside the membrane to increase primary stability and enhance bone integration. ConclusionThe induced-membrane technique is suited to humeral non-union, with or without bone defect. The 2-stage strategy is mandatory in case of suspected latent infection. In the 2-stage procedure, anteromedial radial nerve transposition facilitates the bone-graft stage. Level of evidenceIV, retrospective study.

Outcomes of second-line antiretroviral therapy among children living with HIV: a global cohort analysis.

IntroductionLimited data describe outcomes on second‐line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second‐line ART in the context of routine care within a large global cohort collaboration.MethodsPatient‐level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow‐up were summarized for children who switched to second‐line ART after starting a standard first‐line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub‐Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow‐up (LTFU) were estimated using a competing risks framework.ResultsOf the 85,389 children on first‐line ART, 3,555 (4%) switched to second‐line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second‐line regimens were protease inhibitor‐based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow‐up after switch to second‐line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second‐line ranged from 235 cells/mm3 in SSA to 828 cells/mm3 in North America. Improvements in CD4 counts were observed over two years of follow‐up, particularly in regions with lower CD4 counts at second‐line switch. Improvements in weight‐for‐age z‐scores were not observed during follow‐up. Cumulative incidence of LTFU at two years was <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow‐up in all regions, except Latin America (4.9%) and SSA (5.5%).ConclusionsChildren switched to second‐line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children.

European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations.

IntroductionAchalasia is a primary motor disorder of the oesophagus characterised by absence of peristalsis and insufficient lower oesophageal sphincter relaxation. With new advances and developments in achalasia management, there is an increasing demand for comprehensive evidence-based guidelines to assist clinicians in achalasia patient care.MethodsGuidelines were established by a working group of representatives from United European Gastroenterology, European Society of Neurogastroenterology and Motility, European Society of Gastrointestinal and Abdominal Radiology, and the European Association of Endoscopic Surgery in accordance with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. A systematic review of the literature was performed and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. Recommendations were voted upon using a nominal group technique.ResultsThese guidelines focus on the definition of achalasia, treatment aims, diagnostic tests, medical, endoscopic and surgical therapy, management of treatment failure, follow-up and oesophageal cancer risk.ConclusionThese multidisciplinary guidelines provide a comprehensive evidence-based framework with recommendations on the diagnosis, treatment and follow-up of adult achalasia patients.

The Role of the Clinical Pharmacist in the Management of People Living with HIV in the Modern Antiretroviral Era

As the HIV epidemic has evolved, so too has the role of the clinical pharmacist (CP) in the management of people living with HIV (PLWH). The modern antiretroviral therapy (ART) era has resulted in PLWH living normal life spans with resulting increased comorbidities. CPs have long been a part of the multidisciplinary management of ART. However, with the changing demographics of PLWH and health-care system dynamics, CPs have had the opportunity to expand their role. This includes involvement in managing increasing comorbidities with expanding and more complicated medication regimens, drug interaction monitoring, and optimizing transitions of care, all while recognizing and addressing barriers to successful HIV and hepatitis C virus (HCV) treatment. In addition, with the expansion of HIV prevention and pre-exposure prophylaxis (PrEP) services, CPs have the opportunity to be involved in HIV prevention. This study summarizes the literature evaluating the impact of CPs in the management of PLWH in the era of modern ART. We conducted a literature search to identify studies that assessed the CP role in HIV clinical practice since 2006. The identified studies were grouped into two categories. The first was HIV related outcomes, including interventions on regimen selection, adherence, regimen optimization, and management of treatment failure. The second group of studies pertained to aging and vulnerable populations, including management of comorbidities, transitions of care, medication-assisted treatment, hepatitis C, and HIV screening and PrEP. We concluded that the evidence supports the expanding role of CPs to positively impact a variety of aspects related to the care of PLWH.

Guidelines for the management of human brucellosis in the State of Paraná, Brazil.

Human brucellosis is a re-emerging disease with the potential for bioterrorism. The number of cases in Brazil has increased; however, the ideal management has not been established. These guidelines are intended for use by clinicians and other health-care workers providing medical care for patients with suspected brucellosis in the State of Paraná. We included a brief description of the epidemiology, clinical presentation, diagnosis, prevention of exposure, prevention of disease by chemoprophylaxis, treatment of disease, monitoring of adverse effects during treatment, management of treatment failure and relapse cases.

Recommendations for the treatment of hepatitis B in 2017.

The therapeutic goal which is currently unfrequent but realistic in HBV infected patients is sustained HBsAg clearance. It is preceded by the loss or significant suppression of HBV replication and leads to inhibition of the progression of liver fibrosis, normalization of biochemical indicators of liver damage, reduction in the risk of hepatocellular carcinoma, prolongation of survival, prevention of HBV infection in the transplanted organ in post-transplant patients, enhancement of the quality of life, inhibition or reversal of extrahepatic changes associated with HBV infection, and halting of the spread of HBV infections. Recommendations of Polish Group of Experts for HBV for 2017 provide guidelines to assess treatment eligibility, choice of the first-line drug, monitoring and duration of treatment, management of treatment failure as well as therapy of HBV associated cirrhosis or hepatocellular carcinoma. Moreover it contains advice for treatment of HBV infection in children, females planning pregnancy or pregnant. We also included recommendations for pre- and post-exposure prophylaxis, prevention of HBV transmission from mother to infant, after liver transplantation, on immunosuppressive therapy and during HCV treatment.

Erratum: Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management.

Background Radiofrequency ablation (RFA) is an established treatment for small renal tumors. The objective of this review is to systematically assess the type, frequency, risk factors and management of treatment failure after image-guided percutaneous RFA of renal tumors. Method 10 studies (967 patients, 1033 tumors) with a mean/median follow-up of ≥ 30 months were systematically identified and analyzed. Results and Conclusion Image-guided percutaneous RFA of localized renal tumors is very effective. The most common type of treatment failure is residual unablated tumor (5.9 %), followed by local tumor progression (4.7 %). De novo tumors in the kidneys occur in 1.3 % of cases and extra-renal metastases in 2.0 %. Local tumor progression, de novo tumors in the kidneys and extra-renal metastases occur predominantly later than 12 months after initial RFA. Tumor size > 3 cm and central tumor location are the major risk factors for treatment failure. In the case of treatment failure, repeated RFA shows high success rates (86.3 % for residual unablated tumors and 87.5 % for local tumor progression). Key Points: Citation Format

Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - ASystematic Review with Description of Type, Frequency,Risk Factors and Management.

Background Radiofrequency ablation (RFA) is an established treatment for small renal tumors. The objective of this review is to systematically assess the type, frequency, risk factors and management of treatment failure after image-guided percutaneous RFA of renal tumors. Method 10 studies (967 patients, 1033 tumors) with a mean/median follow-up of ≥ 30 months were systematically identified and analyzed. Results and Conclusion Image-guided percutaneous RFA of localized renal tumors is very effective. The most common type of treatment failure is residual unablated tumor (5.9 %), followed by local tumor progression (4.7 %). De novo tumors in the kidneys occur in 1.3 % of cases and extra-renal metastases in 2.0 %. Local tumor progression, de novo tumors in the kidneys and extra-renal metastases occur predominantly later than 12 months after initial RFA. Tumor size > 3 cm and central tumor location are the major risk factors for treatment failure. In the case of treatment failure, repeated RFA shows high success rates (86.3 % for residual unablated tumors and 87.5 % for local tumor progression). Key Points: · Treatment failure can be subdivided into residual unablated tumor and local tumor progression.. · Residual unablated tumor occurs in 5.9 % of cases.. · Local tumor progression occurs in 4.7 % of cases.. · Tumor size and location are the major risk factors for treatment failure.. · Repeated RFA is effective and commonly used for management.. Citation Format · Vollherbst D, Bertheau R, Kauczor H et al. Treatment Failure After Image-Guided Percutaneous Radiofrequency Ablation (RFA) of Renal Tumors - A Systematic Review with Description of Type, Frequency, Risk Factors and Management. Fortschr Röntgenstr 2017; 189: 219 - 227.

Management of HCV in the liver transplant setting

Hepatitis C-related cirrhosis is the main indication for liver transplantation. In the absence of viral eradication, viral recurrence leads to recurrent HCV disease and progression to advanced graft disease in many recipients, particularly those transplanted with subobtimal grafts. Viral eradication is associated with improved outcome whether used pre- or post-transplantation. In the new era of interferon-free regimes, this is now safe and feasible in most transplant candidates and transplant recipients. There are questions that remain unanswered, such as defining the point of no return where clinical improvement does not follow viral eradication or management of treatment failures.

Diagnostic evaluation for interventional bronchoscopists and radiologists in lung cancer practice.

The global epidemic of lung cancer shows no signs of abating. It is generally accepted that accurate and cost-efficient diagnostic evaluation is the first important step to achieve the best outcomes of treatment. This is true in the context of disease confirmation, treatment planning, treatment monitoring, detection of and management of treatment failure or prognostication. Fortunately, major advances in the diagnostic evaluation of lung cancer have been made in the past three decades allowing more patients to get the appropriate treatment at the right time. This paper outlines how computed tomography, positron emission tomography/computed tomography and endobronchial ultrasound contribute to lung cancer management and discuss their strengths and weaknesses and their complimentary roles at different stages of lung cancer management. Due to financial constraint and reimbursement restrictions, not all clinically important advances in the diagnostic evaluation of lung cancer have been readily accepted into routine clinical care. This enforces the need to maintain ongoing dialogue between cancer clinicians, imaging specialists and health-care economists.

Management of antiviral drug resistance in chronic hepatitis B.

Rescue antiviral treatment for patients with resistance to preexisting nucleos(t)ide analogues remains a clinical challenge. The correct choice of a first-line treatment of high potency and with a high genetic barrier to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and the emergence of drug resistance. The management of treatment failure and drug resistance requires a precise and accurate clinical and virologic monitoring. Combination treatment with antiviral drugs that belong to different groups is associated with a lower chance of developing resistance to rescue drugs. To guarantee better control of viral replication in patients with drug resistance, the addition of another drug without a cross resistance profile should be given as early as possible, preferably at the time when genotypic resistance emerges. Long-term surveillance for treatment efficacy and possible emergence of drug resistance should be continued to prevent the emergence of multidrug-resistant strains.

Executive summary: 2013 update of the guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children.

Major recommendations are accompanied by ratings that include a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation (TABLE 1); this rating system is similar to the rating systems used in other USPHS/IDSA guidelines. Because licensure of drugs for children and their application in clinical care often relies on efficacy data from adult trials in combination with pharmacokinetic, safety, and observational data in children, recommendations sometimes rely on data from clinical trials or studies in adults with supporting data in children. Thus, the quality of evidence level is accompanied by an asterisk (*) to indicate that evidence supporting the recommendation is a hybrid of higher-quality adult study evidence and consistent but lower-quality pediatric study evidence. This modification to the rating system is the same as that used by the DHHS Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Table 1 System for grading strength of recommendations and quality of supporting evidence The guidelines discuss opportunistic illnesses that occur in the United States and ones that might occur during international travel, such as malaria. Because the guidelines target HIV-exposed and -infected children in the United States, the opportunistic pathogens discussed are those common to the United States and do not include certain pathogens such as Penicillium marneffei that may be seen almost exclusively outside the United States. They also do not include pathogens that are common but seldom cause chronic infection, or that have the same risk, disease course, and approach to prevention and treatment in all children regardless of HIV status. Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of first episode of disease; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment, including immune reconstitution inflammatory syndrome (IRIS); management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. The most important, rated recommendations are highlighted in boxed major recommendations sections preceding the text for each OI, and a table of dosing recommendations follows the text for each OI. The tables at the end of the document summarize recommendations for dosing of medications used for prevention and treatment of OIs in children; drug preparation and toxicity information for children; and major drug-drug interactions. Vaccination recommendations for HIV-infected children and adolescents are summarized in the section entitled “Preventing Vaccine-Preventable Diseases in HIV-Infected Children and Adolescents” and individual OI sections and detailed in figures at the end of the document.

S05.1 Antimicrobial Resistance in N. Gonorrhoeae: Update of the Situation

BackgroundThe rapidly changing antimicrobial susceptibility of N. gonorrhoeae since the introduction of antibiotics has created challenges in gonorrhoea control. Antimicrobial resistance has regularly appeared and expanded with every release of...

Treatment switching in South Indian patients on HAART: what are the predictors and consequences?

Early identification and management of treatment failure on highly active antiretroviral therapy (HAART) is crucial in maintaining a sustained response to therapy in HIV infection. However, HIV viral load (VL) and resistance testing, and second-line HAART regimens, are unaffordable to many patients in India, leaving them with limited treatment options. Predictors and reasons for antiretroviral switching, therefore, are likely to differ in settings of varying resources. A one-year, observational study of patients receiving antiretroviral therapy was conducted in a private, non-profit hospital in Bangalore. This paper examines the predictors and consequences of antiretroviral treatment switching in this setting and explores reasons for switching in a subset of patients. Data on demographics, drug regimens, adherence, and physical and psychosocial outcomes were collected quarterly. Tests of VL and CD4 cell counts were performed every six months. One-third of the patients switched therapy during the study period. Baseline predictors of switching included lower CD4 cell counts and more physical symptoms. Contrary to studies in other settings, a high VL did not predict treatment switching, and only a minority of those experiencing drug failure were switched to second-line regimens. Both groups (switchers and non-switchers) improved significantly over time with respect to CD4 counts and psychological well-being, and showed a reduction in physical and depressive symptoms. Any differences between the groups were no longer significant at the end of the study, once we controlled for baseline levels. Clinical, policy, and research implications of these findings are discussed within the context of resource-limited settings.

Challenges to improving case management of childhood pneumonia at health facilities in resource-limited settings.

Effective case management is an important strategy to reduce pneumonia-related morbidity and mortality in children. Guidelines based on sound evidence are available but are used variably. This review outlines current guidelines for childhood pneumonia management in the setting where most child pneumonia deaths occur and identifies challenges for improved management in a variety of settings and different "at-risk" groups. These include appropriate choice of antibiotic, clinical overlap with other conditions, prompt and appropriate referral for inpatient care, and management of treatment failure. Management of neonates, and of HIV-infected or severely malnourished children is more complicated. The influence of co-morbidities on pneumonia outcome means that pneumonia case management must be integrated within strategies to improve overall paediatric care. The greatest potential for reducing pneumonia-related deaths in health facilities is wider implementation of the current guidelines built around a few core activities: training, antibiotics and oxygen. This requires investment in human resources and in equipment for the optimal management of hypoxaemia. It is important to provide data from a variety of epidemiological settings for formal cost-effectiveness analyses. Improvements in the quality of case management of pneumonia can be a vehicle for overall improvements in child health-care practices.