Surgical intervention and long-term renal outcomes of congenital ureteropelvic junction obstruction in a young adult cohort.

PURPOSE: To evaluate the impact of surgical intervention on long-term renal outcomes for adult patients with congenital ureteropelvic junction obstruction (UPJO). METHODS: We queried service members diagnosed with UPJO from the United States Military Health System electronic health records from 2005 to 2020. We assessed demographic, laboratory, radiology, surgical intervention, and outcome data. We evaluated the impact of surgical intervention on renal function based on the estimated glomerular filtration rate (eGFR), hypertension (HTN, defined as any prescription for blood pressure [BP] medication and/or average of two BP readings ≥ 130/80 mmHg more than 2 weeks apart), and changes in renal excretory function on radionuclide scans. RESULTS: We identified 108 individuals diagnosed with congenital UPJO; mean follow-up of 7 years. Mean age at diagnosis was 25 years; 95% male; 69% White, 15% Black. At diagnosis, median BP was 130/78 mmHg and mean eGFR 93 ml/min/1.73m2. Subsequently, 85% had pyeloplasty and 23% had stent placement. There were no significant differences in mean eGFR pre- and post-intervention (94 vs. 93 ml/min/1.73m2, respectively; p = 0.15) and prevalence of defined HTN (59% vs. 61%, respectively; p = 0.20). Surgical intervention for right-sided UPJO significantly reduced the proportion of patients with delayed cortical excretion (54% pre vs. 35% post, p = 0.01) and T½ emptying time (35 min vs. 19 min, p = 0.009). Similar trends occurred with left-sided UPJO but were not significant. CONCLUSION: Surgical intervention was not associated with significant differences in the long-term outcomes of kidney function and HTN prevalence in our young adult cohort. However, renal excretory function improved on radionuclide scans.

Brachytherapy for rectal and anal cancer: Where are we and current perspectives?

Anal and rectal cancers were some of the first disease sites treated with brachytherapy due to the anatomic ease of implantation. As external beam radiotherapy grew in popularity the use of ano-rectal brachytherapy declined. However, the past few years have seen a steady resurgence in the use of brachytherapy in the ano-rectum supported by the use of large clinical series and randomized trials. The increasing acceptance by the surgical community of organ preservation as a valid treatment strategy for rectal cancer has encouraged the use of nonsurgical approaches and brachytherapy has shown itself to be a valuable tool for this. The current role of anal and rectal brachytherapy is presented with perspectives on its future use.

Implementing cone-beam computed tomography-guided online adaptive radiotherapy in cervical cancer.

Background and purpose: Adaptive radiotherapy (ART) in locally advanced cervical cancer (LACC) has shown promising outcomes. This study investigated the feasibility of cone-beam computed tomography (CBCT)-guided online ART (oART) for the treatment of LACC. Material and methods: The quality of the automated radiotherapy treatment plans and artificial intelligence (AI)-driven contour delineation for LACC on a novel CBCT-guided oART system were assessed. Dosimetric analysis of 200 simulated oART sessions were compared with standard treatment. Feasibility of oART was assessed from the delivery of 132 oART fractions for the first five clinical LACC patients. The simulated and live oART sessions compared a fixed planning target volume (PTV) margin of 1.5 cm around the uterus-cervix clinical target volume (CTV) with an internal target volume-based approach. Workflow timing measurements were recorded. Results: The automatically-generated 12-field intensity-modulated radiotherapy plans were comparable to manually generated plans. The AI-driven organ-at-risk (OAR) contouring was acceptable requiring, on average, 12.3 min to edit, with the bowel performing least well and rated as unacceptable in 16 % of cases. The treated patients demonstrated a mean PTV D98% (+/-SD) of 96.7 (+/- 0.2)% for the adapted plans and 94.9 (+/- 3.7)% for the non-adapted scheduled plans (p<10-5). The D2cc (+/-SD) for the bowel, bladder and rectum were reduced by 0.07 (+/- 0.03)Gy, 0.04 (+/-0.05)Gy and 0.04 (+/-0.03)Gy per fraction respectively with the adapted plan (p <10-5). In the live.setting, the mean oART session (+/-SD) from CBCT acquisition to beam-on was 29 +/- 5 (range 21-44) minutes. Conclusion: CBCT-guided oART was shown to be feasible with dosimetric benefits for patients with LACC. Further work to analyse potential reductions in PTV margins is ongoing.

Pain and symptom relief using inhaled methoxyflurane for gynecologic brachytherapy applicator removal.

Purpose: Intra-cavitary brachytherapy forms an essential part of the curative treatment of cervical and vaginal cancer, and can be used for cure or palliation in endometrial and vulval cancers. Removal of brachytherapy applicators is often performed after anaesthesia has worn off and can be an uncomfortable and anxiety-provoking procedure. In this paper, we present our experience in a series of patients before and after the introduction of inhaled methoxyflurane (IMF, Penthrox™). Material and methods: Questionnaires were sent to patients prior to the introduction of IMF to retrospectively score pain and anxiety during the brachytherapy procedure. Following successful review by the local drugs and therapeutic committee as well as staff training, IMF was introduced and offered to patients during applicator removal. Prospective pain scores and retrospective questionnaires were collected. Pain was rated on a scale of 0 to 10, with zero being no pain and 10 being extreme pain. Results: Thirteen patients returned retrospective questionnaires prior to IMF introduction and seven patients following IMF introduction. After the first brachytherapy insertion, the mean recollected pain score during applicator removal decreased from 6/10 to 1/10 (p = 0.002). The mean recollected pain score one hour after applicator removal reduced from 3/10 to 0 (p = 0.04). Prospective measurements for 77 insertions in 44 patients receiving IMF reported a median pain score of 1/10 immediately before applicator removal (range, 0-10), and 0/10 immediately after applicator removal (range, 0-5). Conclusions: Inhaled methoxyflurane is easily administered and effective method of decreasing pain during applicator removal following gynecologic brachytherapy.

Consensus on level descriptors for a functional children's eating and drinking activity scale.

AIM: To agree wording of level descriptors for a measure of functional outcome of children's eating and drinking. METHOD: An online, modified Delphi method was used to gather feedback on current level descriptor wording and generate rewording suggestions. Thirty speech and language therapists, working in a variety of settings and geographical locations, were invited to be part of the Delphi expert panel. Content analysis was used to evaluate participants' comments and develop consensus level descriptors. Consensus for acceptable wording was set at 80% agreement. Face validity was assessed using 5-point Likert scales. RESULTS: Nineteen expert speech and language therapists (median experience 18 years) completed round one; 15 out of 19 completed round two. Level descriptor rating reached 80% agreement in two rounds. Additionally, 93% of participants agreed the scale would accurately capture change in their setting, with 87% likely to use the scale in practice. INTERPRETATION: This study has produced agreed wording for a functional measure of eating and drinking activity suitable for use with paediatrics feeding disorders, regardless of disease aetiology, presentation, age, or setting. Potential for widespread use is supported. Further evaluation of the tool's reliability and validity is required.

Planned organ preservation for elderly patients with rectal cancer using short course radiotherapy and a contact brachytherapy boost-an International multi-institution analysis.

Background and purpose: The use of external beam radiotherapy (EBRT) and contact X-Ray brachytherapy (CXB) is emerging as an effective alternative in patients with early stage rectal cancer with the intent of organ preservation (OP). Short course radiotherapy (SCRT) is an alternative EBRT schedule for patients not fit for chemotherapy or for longer courses of EBRT. There are no multicentre studies that have reported on the outcomes of SCRT with a CXB boost, therefore we present these from patients from centres from the UK and Sweden. Materials and methods: From the Guildford Colorectal Database or local databases, 258 patients who underwent SCRT and CXB with the intent of OP from five centres treated between 2007 and 2019 were identified. Response and survival data was analysed and presented. Results: With a median age of 81, 226 patients were treated with radiotherapy alone (RTA) and 32 immediately after local excision (ILE). Median follow-up was 24 months. 70% and 97% of patients in the RTA and ILE groups respectively had a complete clinical response (cCR) after SCRT with CXB. Of those, local relapse was seen in 16% of the RTA and 3% of the ILE group. Median survival was 40 months after CXB in the RTA and 52 months in the ILE group. 94% of patients remained stoma-free to the point of latest follow-up. Conclusion: This data suggests that CXB when combined with SCRT, in a mainly elderly and comorbid population, provides good palliation with stoma-avoidance. Oncological outcomes compare with previously published work. A greater focus is required on quality of life outcomes after OP.

Enhanced Recovery after Uterine Corpus Cancer Surgery: A 10 Year Retrospective Cohort Study of Robotic Surgery in an NHS Cancer Centre.

Royal Surrey NHS Foundation Trust introduced robotic surgery for uterine corpus cancer in 2010 to support increased access to minimally invasive surgery, a central element of an enhanced recovery after surgery (ERAS) pathway. More than 1750 gynaecological oncology robotic procedures have now been performed at Royal Surrey NHS Foundation Trust. A retrospective cohort study was performed of patients undergoing surgery for uterine corpus cancer between the 1 January 2010 and the 31 December 2019 to evaluate its success. Data was extracted from the dedicated gynaecological oncology database and a detailed notes review performed. During this time; 952 patients received primary surgery for uterine corpus cancer; robotic: n = 734; open: n = 164; other minimally invasive surgery: n = 54. The introduction of the Da VinciTM robot to Royal Surrey NHS Foundation Trust was associated with an increase in the minimally invasive surgery rate. Prior to the introduction of robotic surgery in 2008 the minimally invasive surgery (MIS) rate was 33% for women with uterine corpus cancer undergoing full surgical staging. In 2019, 10 years after the start of the robotic surgery program 91.3% of women with uterine corpus cancer received robotic surgery. Overall the MIS rate increased from 33% in 2008 to 92.9% in 2019. Robotic surgery is associated with a low 30-day mortality (0.1%), low return to theatre (0.5%), a low use of blood transfusion and intensive care (1.8% & 7.2% respectively), low conversion to open surgery (0.5%) and a reduction in median length of stay from 6 days (in 2008) to 1 day, regardless of age/BMI. Robotic survival is consistent with published data. Introduction of the robotic program for the treatment of uterine cancer increased productivity and was associated with a highly predicable patient pathway of care, for high-risk patients, with reduced demands on health services. Future health care commissioning should further expand access to robotic surgery nationally for women with uterine corpus cancer.

Parents' experiences of feeding children born with oesophageal atresia/tracheo-oesophageal fistula.

BACKGROUND: Feeding difficulties are widely acknowledged following oesophageal atresia/tracheo-oesophageal fistula repair. However, little is understood about the nature and severity of these difficulties. This study explored feeding in children with oesophageal atresia/tracheo-oesophageal fistula from the parent perspective. METHODS: In collaboration with a patient support group, data were collected using a research-specific online discussion forum. Thematic analysis was used to code the data and identify themes. RESULTS: One hundred and twenty-seven parents registered for the online forum, of whom 83 (65%) provided demographic data. Seventy-four (89%) of responders were mothers, 75 (90%) were of white ethnicity, 65 (78%) were from the UK. Six key themes were identified: feeding is a traumatic experience, feeding my child is scary, feeding is isolating and filled with uncertainty, feeding outside of the home is difficult, feeding associated emotions, developing coping strategies. Parents described features of medical, nutritional, feeding skill and psychosocial dysfunction across all stages of eating/drinking development. They described how their child's feeding difficulties had an impacted their own well-being. An interactional model of feeding difficulties in OA/TOF is proposed. CONCLUSIONS: Exploring parent experiences provides rich data from which to expand understanding of the complex nature of feeding difficulties in OA/TOF. Feeding should be viewed as a dyadic process, occurring within a family system. Intervention for feeding difficulties should be family-centred, addressing parental anxiety, trauma and uncertainty, as well as the child's underlying medical/surgical needs to optimise outcome. Further study of clinical correlates with parental experience is required. LEVEL OF EVIDENCE: IV (non-experimental, qualitative).

Endorectal contact radiation boosting: Making the case for dose AND volume reporting.

INTRODUCTION: The various rectal endoluminal radiation techniques all have steep, but different, dose gradients. In rectal contact brachytherapy (CXB) doses are typically prescribed and reported to the applicator surface and not to the gross tumor volume (GTV), clinical target volume (CTV) or organs at risk (OAR), which is crucial to understand tumor response and toxicity rates. To quantify the above-described problem, we performed a dose modeling study using a fixed prescription dose at the surface of the applicator and varied tumor response scenarios. METHODS: Endorectal ultrasound-based 3D-volume-models of rectal tumors and the rectal wall were used to simulate the delivered dose to GTV, CTV and the rectal wall layers, assuming treatment with Maastro HDR contact applicator for rectal cancer with a fixed prescription dose to the applicator surface (equivalent to 3 × 30 Gy CXB) and various response scenarios. RESULTS: An identical prescribed dose to the surface of the applicator resulted in a broad range of doses delivered to the GTV, CTV and the uninvolved intestinal wall. For example, the equieffective dose in 2 Gy per fraction (EQD2) D90% of the GTV varied between 63 and 231 Gy, whereas the EQD2 D2cc of the rectal wall varied between 97 and 165 Gy. CONCLUSION: Doses prescribed at the surface are not representative of the dose received by the tumor and the bowel wall. This stresses the relevance of dose reporting and prescription to GTV and CTV volumes and OAR in order to gain insight between delivered dose, local control and toxicity and to optimize treatment protocols.

Microsporidial myositis, keratitis and hypercalcaemia in a cystic fibrosis lung transplant recipient.

A man in his 50s was admitted with 4 months of myalgia, headaches, hypercalcaemia and declining renal function on a background of lung transplantation for cystic fibrosis 5 years prior. MRI confirmed myositis and a muscle biopsy revealed invasive muscular microsporidial infection. Positron emission tomography(PET)/CT revealed widespread dissemination of the infection. Albendazole was commenced and after a 1 week systemic inflammatory response syndrome, the patient made a significant recovery and was discharged home. PCR testing confirmed the species as Anncaliia algerae, which is known to infect mosquitoes, larvae and contaminate water supplies. This case highlights the need to relentlessly pursue a diagnosis and to consider atypical pathology in immune compromised patients. A tissue sample yielded highly beneficial and unexpected results. A multispecialty approach was essential given the varied infection manifestations, which included myositis, keratitis and possible central nervous system, vocal cord, parapharyngeal and renal involvement.

GEC ESTRO ACROP consensus recommendations for contact brachytherapy for rectal cancer.

PURPOSE: To issue consensus recommendations for contact X-Ray brachytherapy (CXB) for rectal cancer covering pre-treatment evaluation, treatment, dosimetric issues and follow-up. These recommendations cover CXB in the definitive and palliative setting. METHODS: Members of GEC ESTRO with expertise in rectal CXB issued consensus-based recommendations for CXB based on literature review and clinical experience. Levels of evidence according to the Oxford Centre for Evidence based medicine guidance are presented where possible. RESULTS: The GEC ESTRO ACROP consensus recommendations support the use of CXB to increase the chances of clinical complete remission and cure for patients who are elderly with high surgical risk, surgically unfit or refusing surgery. For palliative treatment, the use of CXB is recommended for symptomatic relief and disease control. The use of CXB in an organ-preservation setting in surgically fit patients is recommended within the setting of a clinical trial or registry. CONCLUSIONS: The GEC ESTRO ACROP recommendations for CXB are provided. Recommendations towards standardisation of reporting and prescription are given. Practitioners are encouraged to follow these recommendations and to develop further clinical trials to examine this treatment modality and increase the evidence base for its use. The routine collection of outcomes both clinical and patient-reported is also encouraged.

Research Priorities for Pediatric Intensive Care Nutrition Within the United Kingdom: A National Institute of Health Research James Lind Alliance Priority Setting Partnership.

OBJECTIVES: To determine research priorities in PICU nutrition, which represent the shared priorities of patients, parents, carers, and PICU healthcare professionals within the United Kingdom. DESIGN: A national multiphase priority setting methodology in partnership with the James Lind Alliance delivered over 16 months (June 2020-September 2021). Part 1: a national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. Part 2: summarizing and evidence-checking the submitted uncertainties. Part 3: interim prioritization survey. Part 4: consensus workshop. SETTING: PICU. PARTICIPANTS: Patients, parents, and carers of patients who had been admitted to PICU, and PICU healthcare professionals involved in the treatment of these patients within the United Kingdom. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition. In the first survey, 165 topic ideas were suggested (12% by parents/carers and 88% by PICU healthcare professionals). These were categorized into 57 summary questions. The existing evidence was searched to ensure that the proposed summary questions had not already been answered. Forty were judged to be true uncertainties following a systematic literature review. These 40 uncertainties were grouped into eight themes for the second interim survey, which asked respondents to prioritize their top research questions. One hundred and forty participants contributed to this second interim survey. A final shortlist of 25 questions was derived, with the top 18 questions taken to a multistakeholder workshop where a consensus was reached on the top 10 priorities. CONCLUSIONS: This research identified important research gaps in the management of patients in PICU. Areas that need to be addressed as a priority include energy requirements in ventilated neonates, nutritional supplementation of probiotics to manage and prevent sepsis, the impact of postintensive care syndrome on nutrition and growth, and when to commence parenteral (IV) nutrition. The challenge now is to refine and deliver answers to these research priorities.

Evolution of bulbar function in spinal muscular atrophy type 1 treated with nusinersen.

AIM: To assess the evolution of bulbar function in nusinersen-treated spinal muscular atrophy type 1 (SMA1). METHOD: This single-centre retrospective study identified 24 patients (14 females and 10 males) with SMA1, treated with nusinersen between 2017 and 2020. We adapted and validated the Paediatric Functional Oral Intake Scale (p-FOIS), which is an outcome measure to assess bulbar function. Analysis considered SMA1 subtype, nutritional support, and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and p-FOIS scores at initiation of nusinersen treatment (baseline) and at 6, 12, and 24 months after initiation. RESULTS: The median age at baseline was 11 months (range 1 month-7 years 6 months). Median age at initiation of tube feeding was 8 months (range 0-2 years 2 months). Fourteen patients were tube fed at baseline. The median p-FOIS score was 3 at baseline and 2 at 12 and 24 months. Four patients, all with type 1c SMA, remained orally fed at 24 months. Median CHOP INTEND scores increased from 32 at baseline to 42 at 12 and 24 months. INTERPRETATION: Impaired bulbar function persisted as a significant complication in most nusinersen-treated patients with SMA1, in contrast to the improvement in motor abilities demonstrated in the majority. p-FOIS allows for tracking of bulbar function progression and treatment response. Larger, prospective studies investigating the longer-term impacts of nusinersen on bulbar function are warranted.

More than a roof; challenges for older women renters in British Columbia, Canada.

The growing issue of housing affordability is an increasing challenge worldwide as the financialization of housing markets undermines housing as a basic human right. One of the most vulnerable segments of the population affected by rising housing costs are older, low-income, females. Drawing on qualitative interviews with older women, we explore lived experiences of housing insecurity using a feminist political ecology perspective. Our findings reveal substantial challenges as well as creative solutions being employed by these women to stay in place. We conclude that more targeted and age- and gender-inclusive housing policies, programs, supports and services are critically needed.

The seasonality of infections in tropical Far North Queensland, Australia: A 21-year retrospective evaluation of the seasonal patterns of six endemic pathogens.

An understanding of the seasonality of infections informs public health strategies and assists clinicians in their management of patients with undifferentiated illness. The seasonality of infections is driven by a variety of environmental and human factors; however, the role of individual climatic factors has garnered much attention. This study utilises Poisson regression models to assess the seasonality of six important infections in tropical Australia and their association with climatic factors and severe weather events over a 21-year period. Melioidosis and leptospirosis showed marked wet season predominance, while more cases of rickettsial disease and cryptococcosis were seen in cooler, drier months. Staphylococcus aureus infections were not seasonal, while influenza demonstrated inter-seasonality. The climate did not significantly change during the 21 years of the study period, but the incidence of melioidosis and rickettsial disease increased considerably, highlighting the primacy of other factors-including societal inequality, and the impact of urban expansion-in the incidence of these infections. While anthropogenic climate change poses a threat to the region-and may influence the burden of these infections in the future-this study highlights the fact that, even for seasonal diseases, other factors presently have a greater effect on disease incidence. Public health strategies must also target these broader drivers of infection if they are to be effective.

Genetic Variation of G6PD and CYP2D6: Clinical Implications on the Use of Primaquine for Elimination of Plasmodium vivax.

Primaquine, an 8-aminoquinoline, is the only medication approved by the World Health Organization to treat the hypnozoite stage of Plasmodium vivax and P. ovale malaria. Relapse, triggered by activation of dormant hypnozoites in the liver, can occur weeks to years after primary infection, and provides the predominant source of transmission in endemic settings. Hence, primaquine is essential for individual treatment and P. vivax elimination efforts. However, primaquine use is limited by the risk of life-threatening acute hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. More recently, studies have demonstrated decreased efficacy of primaquine due to cytochrome P450 2D6 (CYP2D6) polymorphisms conferring an impaired metabolizer phenotype. Failure of standard primaquine therapy has occurred in individuals with decreased or absent CYP2D6 activity. Both G6PD and CYP2D6 are highly polymorphic genes, with considerable geographic and interethnic variability, adding complexity to primaquine use. Innovative strategies are required to overcome the dual challenge of G6PD deficiency and impaired primaquine metabolism. Further understanding of the pharmacogenetics of primaquine is key to utilizing its full potential. Accurate CYP2D6 genotype-phenotype translation may optimize primaquine dosing strategies for impaired metabolizers and expand its use in a safe, efficacious manner. At an individual level the current challenges with G6PD diagnostics and CYP2D6 testing limit clinical implementation of pharmacogenetics. However, further characterisation of the overlap and spectrum of G6PD and CYP2D6 activity may optimize primaquine use at a population level and facilitate region-specific dosing strategies for mass drug administration. This precision public health approach merits further investigation for P. vivax elimination.

Dysphagia rehabilitation following acquired brain injury, including cerebral palsy, across the lifespan: a scoping review protocol.

BACKGROUND: Swallowing impairment (dysphagia) following brain injury can lead to life-threatening complications such as dehydration, aspiration pneumonia and acute choking episodes. In adult therapeutic practice, there is research and clinical evidence to support the use of swallowing exercises to improve swallowing physiology in dysphagia; however, the use of these exercises in treating children with dysphagia is largely unexplored. Fundamental questions remain regarding the feasibility and effectiveness of using swallowing exercises with children. This review aims to outline the published literature on exercise-based treatment methods used in the rehabilitation of dysphagia secondary to an acquired brain injury across the lifespan. This will allow the range and effects of interventions utilised to be mapped alongside differential practices between adult and child populations to be formally documented, providing the potential for discussions with clinicians about which rehabilitative interventions might be appropriate for further trial in paediatrics. METHODS: This study will use a scoping review framework to identify and systematically review the existing literature using Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Reviews (PRISMA) scoping review guidelines. Electronic databases (MEDLINE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Allied and Complementary Medicine Database (AMED)), grey literature and the reference lists of key texts including systematic reviews will be searched. Information about the rehabilitation design, dosage and intensity of exercise programmes used as well as demographic information such as the age of participants and aetiology of dysphagia will be extracted. The number of articles in each area and the type of data source will be presented in a written and visual format. Comparison between the literature in adult and child populations will be discussed. DISCUSSION: This review is unique as it directly compares dysphagia rehabilitation in adults with that of a paediatric population in order to formally identify and discuss the therapeutic gaps in child dysphagia rehabilitation. The results will inform the next stage of research, looking into the current UK-based speech and language therapy practices when working with children with acquired dysphagia. SYSTEMATIC REVIEW REGISTRATION: Open science framework osf.io/ja4dr.

The Applicability of Commonly Used Severity of Illness Scores to Tropical Infections in Australia.

Many patients with leptospirosis, melioidosis, and rickettsial infection require intensive care unit (ICU) admission in tropical Australia every year. The multi-organ dysfunction associated with these infections results in significantly elevated severity of illness (SOI) scores. However, the accuracy of these SOI scores in predicting death from these tropical infections is incompletely defined. This retrospective study was performed at Cairns Hospital, a tertiary-referral hospital in tropical Australia. All patients admitted to ICU with laboratory-confirmed leptospirosis, melioidosis, and rickettsial disease between January 1, 1999 and June 30, 2020, were eligible for the study. The ability of Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Simplified Acute Physiology Scores (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores to predict death before ICU discharge was evaluated. Overall, 18 (12.1%) of the 149 included patients died: 15/74 (20.3%) with melioidosis, 2/54 (3.7%) with leptospirosis and 1/21 (4.8%) with rickettsial disease. However, the APACHE II, APACHE III, SAPS II, and SOFA scores significantly overestimated the case-fatality rate of all the infections; the disparity between the predicted and observed mortality was most marked in the cases of leptospirosis and rickettsial disease. Commonly used SOI scores significantly overestimate the case-fatality rate of melioidosis, leptospirosis, and rickettsial infections in Australian ICU patients. This may be at least partly explained by the unique pathophysiology of these infections, particularly leptospirosis and rickettsial disease. However, SOI scores may still be useful in facilitating the comparison of disease severity in clinical trials that examine patients with these pathogens.

An Update on the Laboratory Diagnosis of Rickettsia spp. Infection.

Rickettsia species causing human illness are present globally and can cause significant disease. Diagnosis and identification of this intracellular bacteria are challenging with many available diagnostic modalities suffering from several shortcomings. Detection of antibodies directed against Rickettsia spp. via serological methods remains widely used with a broad range of sensitivity and specificity values reported depending on the assay. Molecular methods, including polymerase chain reaction (PCR) testing, enables species-specific identification with a fast turnaround time; however, due to resource requirements, use in some endemic settings is limited. Reports on the use of next-generation sequencing (NGS) and metagenomics to diagnose Rickettsia spp. infection have been increasing. Despite offering several potential advantages in the diagnosis and surveillance of disease, genomic approaches are currently only limited to reference and research laboratories. Continued development of Rickettsia spp. diagnostics is required to improve disease detection and epidemiological surveillance, and to better understand transmission dynamics.