Antiviral therapies for the management of persistent coronavirus disease 2019 in immunocompromised hosts: A narrative review.

Antiviral agents with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have played a critical role in disease management; however, little is known regarding the efficacy of these medications in the treatment of SARS-CoV-2 infection in immunocompromised patients, particularly in the management of persistent SARS-CoV-2 positivity. This narrative review discusses the management of persistent coronavirus disease 2019 in immunocompromised hosts, with a focus on antiviral therapies. We identified 84 cases from the literature describing a variety of approaches, including prolonged antiviral therapy (n = 11), combination antivirals (n = 13), and mixed therapy with antiviral and antibody treatments (n = 60). A high proportion had an underlying haematologic malignancy (n = 67, 80%), and were in receipt of anti-CD20 agents (n = 51, 60%). Success was reported in 70 cases (83%) which varied according to the therapy type. Combination therapies with antivirals may be an effective approach for individuals with persistent SARS-CoV-2 positivity, particularly those that incorporate treatments aimed at increasing neutralizing antibody levels. Any novel approaches taken to this difficult management dilemma should be mindful of the emergence of antiviral resistance.

Early oral antibiotic switch in Staphylococcus aureus bacteraemia: The Staphylococcus aureus Network Adaptive Platform (SNAP) Trial Early Oral Switch Protocol.

BACKGROUND: Staphylococcus aureus bloodstream infection (bacteraemia) is traditionally treated with at least two weeks of IV antibiotics in adults, 3-7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteraemia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients. PROTOCOL: The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 +/- 2 (uncomplicated SAB) and day 14 +/-2 (complicated SAB) to determine their eligibility for randomisation to EOS (intervention) or continued IV treatment (current standard of care). DISCUSSION: Recruitment is occurring to the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomised to the EOS domain, a total of 264 participants across 77 centres, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials.

Survey of treatment practices for immunocompromised patients with COVID-19 in Australasia.

Coronavirus disease 2019 (COVID-19) in immunocompromised patients can lead to severe and prolonged illness. Data are limited with regard to management of COVID-19 in this setting, particularly in persistent or recrudescent infection. The authors conducted an online survey among infectious diseases doctors to determine current approaches to treatment across Australasia. There was marked variability in responses relating to the diagnostic modalities and use of antiviral agents in patients with immunocompromise, highlighting the need for high-quality studies to guide treatment decisions in this group.

Worth the risk? Contemporary indications, yield and complications of lumbar punctures in a metropolitan Australian health service.

BACKGROUND: Performing lumbar punctures carries a risk of harm to the patient, but the information cerebrospinal fluid provides often makes this procedure necessary. Clinicians in the Australian setting would benefit from having more information on these procedures, in order to help them in a risk versus benefit analysis. AIMS: To describe the contemporary indications, cerebrospinal fluid findings and complications of lumbar punctures in a metropolitan Australian health service. METHODS: Retrospective electronic medical records audit of lumbar punctures performed on 525 adults within three acute hospitals between 1 July 2018 and 30 June 2019. Main outcome measures include frequency of indication for lumbar puncture by category, normal versus abnormal cerebrospinal fluid for each category, and frequency, severity and type of complications of lumbar punctures. RESULTS: Of 525 adult lumbar punctures that were assessed in this study, 466 were performed for a diagnostic indication. The most common diagnostic indications were acute severe headache (156 procedures; 33.5%) and encephalopathy (128 procedures; 27.5%). The yield of abnormal results varied by indication category, with the above indications yielding abnormal results in 85 (54.5%) and 72 (56.3%) cases respectively. A complication was recorded in 54 (10.3% of total) procedures. The majority (45; 8.6%) of complications were minor in severity and most frequently consisted of post-dural puncture headache (PDPH). CONCLUSIONS: In the era of an increased reliance on high quality neuroimaging, lumbar puncture has a high diagnostic yield with a low rate of major complications. The most common complication is PDPH, which is mild and self-limiting in most cases.

Impact of SARS-CoV-2 transmission-based precautions on inpatient management of general medical patients.

This audit reviewed the impact on access to routine medical care and adverse outcomes in patients with suspected SARS-CoV-2 infection managed on a 'COVID-19' (CV) ward compared with a general medicine ward at Box Hill Hospital, Victoria. Data were collected at two time points to capture changes associated with onsite testing. We found no healthcare delays from admission to CV wards and observed faster exits from CV wards with improved testing efficiency. This critical finding is relevant as Victoria manages a third wave of infections.

Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal ß-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial.

Importance: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a ß-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective: To determine whether combining an antistaphylococcal ß-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions: Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal ß-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the ß-lactam was administered for 7 days. Main Outcomes and Measures: The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results: The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, -4.2%; 95% CI, -14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, -3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, -8.9%; 95% CI, -16.6% to -1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance: Among patients with MRSA bacteremia, addition of an antistaphylococcal ß-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02365493.

Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience.

Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents ∼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively. We present key clinical data, including a granular patient-level analysis of the associations of antiretroviral therapy regimens with long-term survival, cellular and antibody-mediated rejection rates, and the causes of allograft failures. In summary, we provide details on the evolution of our approach to HIV transplantation during the last 16 years, including strategies that may improve outcomes among HIV-positive kidney transplantation candidates throughout the United States.

Association Between Weight Loss Before Deceased Donor Kidney Transplantation and Posttransplantation Outcomes.

RATIONALE & OBJECTIVE: There is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT. EXPOSURES: Relative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain. OUTCOMES: We examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality. ANALYTIC APPROACH: Unadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models. RESULTS: Among 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality. LIMITATIONS: Unmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error. CONCLUSIONS: DDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

Actinomyces spp. bloodstream and deep vein thrombus infections in people who inject drugs.

INTRODUCTION: Actinomyces spp. cause several well-described syndromes including cervicofacial and pelvic infections. Actinomyces spp. infection as an opportunistic infection among people who inject drugs has rarely been described with few case reports published. METHODS AND RESULTS: Here we describe four people who inject drugs admitted with Actinomyces spp. infections, all with an overlapping syndrome and who presented a challenge to both diagnose and to manage. DISCUSSION: This case series highlights the potential to overlook Actinomyces spp. infection in people who inject drugs and aims to increase clinician awareness of diagnosis, empirical and directed treatment, and potential complications of this infection.

Developing a Sustainable Renal Transplant Program in Low- and Middle-Income Countries: Outcome, Challenges, and Solutions.

INTRODUCTION: The initiation of a kidney transplant program, in a low- and middle-income country, while striving to maintain excellent outcomes and adhere to high ethical, legal standards, is a formidable task. Herein, we review the outcomes and challenges of a living donor kidney transplant program from its inception to sustainability, in Guyana, South America. METHODS: This is a retrospective review of a living donor kidney transplant program instituted in Guyana in 2008. Data included recipient and donor demographics, cause of renal failure, donor-recipient matching and relationship, perioperative complications, timing and cause of death, graft failure, surgical technique, and laterality of organ procured. Patient and donor data were compared by phases and additionally compared to United States Renal Data Base System. Survival outcomes were compared by phases and by Kaplan-Meier curves. RESULTS: To date, 45 kidney transplants have been completed. Phase I (2007-2008) was the initiation of the program, which was comprised of upgrading hospital and operating rooms, obtaining antirejection medications, educating local providers, fostering a relationship with the government, and screening patients and living donors. We also began vascular access and peritoneal dialysis in the country, as well as introduced the companion public health service initiative: the SEVAK program. Phase II (2008-2014) involved completion of 25 living donor kidney transplants, of which there have been 11 confirmed deaths and 10 lost to follow-up. In Phase III (2015-present), 20 transplants have been completed to date, of whom only 1 died and none were lost to follow-up. In the third phase, we also introduced corneal transplantation to Guyana and have performed over 100 transplants. CONCLUSION: Kidney transplantation can be safely and ethically performed in a low- and middle-income country. We applied lessons learnt from the first two phases to improve follow-up by appointing a local coordinator who goes to patient's homes in remote villages. Currently, there is a stable local team that is performing transplants and following the patients. We believe that our model of public-private partnership can sustain kidney, as well as corneal, transplantation and could be replicated in other countries.

Association of the kidney allocation system with dialysis exposure before deceased donor kidney transplantation by preemptive wait-listing status.

BACKGROUND: It is unknown whether the new kidney transplant allocation system (KAS) has attenuated the advantages of preemptive wait-listing as a strategy to minimize pretransplant dialysis exposure. METHODS: We performed a retrospective study of adult US deceased donor kidney transplant (DDKT) recipients between December 4, 2011-December 3, 2014 (pre-KAS) and December 4, 2014-December 3, 2017 (post-KAS). We estimated pretransplant dialysis durations by preemptive listing status in the pre- and post-KAS periods using multivariable gamma regression models. RESULTS: Among 65 385 DDKT recipients, preemptively listed recipients (21%, n = 13 696) were more likely to be white (59% vs 34%, P < 0.001) and have private insurance (64% vs 30%, P < 0.001). In the pre- and post-KAS periods, average adjusted pretransplant dialysis durations for preemptively listed recipients were <2 years in all racial groups. Compared to recipients who were listed after starting dialysis, preemptively listed recipients experienced 3.85 (95% Confidence Interval [CI] 3.71-3.99) and 4.53 (95% CI 4.32-4.74) fewer average years of pretransplant dialysis in the pre- and post-KAS periods, respectively (P < 0.001 for all comparisons). CONCLUSIONS: Preemptively wait-listed DDKT recipients continue to experience substantially fewer years of pretransplant dialysis than recipients listed after dialysis onset. Efforts are needed to improve both socioeconomic and racial disparities in preemptive wait-listing.

Delays in presentation and diagnosis of pulmonary tuberculosis: a retrospective study of a tertiary health service in Western Melbourne, 2011-2014.

BACKGROUND: Effective tuberculosis (TB) control relies on early diagnosis and prompt treatment commencement. AIM: To investigate delays in presentation and diagnosis of pulmonary TB (PTB) in a low incidence setting in Western Melbourne. METHODS: A single-centred retrospective observational cohort study of symptomatic patients ≥ 18 years newly diagnosed with PTB that were commenced on treatment between 1 December 2011 and 1 December 2014 at a tertiary teaching hospital in Western Melbourne. Main outcome measures included median duration of patient, health system and total delays to diagnosis of PTB and clinical factors associated with prolonged patient (>35 days) and health system (>21 days) delay. RESULTS: A total of 133 patients were included. The median (range) duration of patient, health system and total delay to diagnosis were 28 (0-610), 18 (0-357) and 89 (1-730) days respectively. Prolonged patient delay was associated with being from a country with an annual TB incidence of <50/100 000 (odds ratio (OR) 5.98, 95% confidence interval (CI) 1.19, 29.98) and diabetes mellitus (OR 3.02, 95% CI 1.04, 8.78) in multivariate analysis. Being Australian-born or a resident of Australia ≥6 years (OR 0.03, 95% CI 0.12, 0.74; OR 0.30, 95% CI 0.00, 0.033 respectively) was associated with reduced patient delay. CONCLUSIONS: In this low-incidence, high-resource setting, patient delays contribute most to total delay in PTB diagnosis. Strategies addressing this aspect of the TB diagnosis pathway, such as health literacy and promotion programmes for new migrants and raised primary healthcare awareness, could have the largest impact on reducing total PTB diagnosis delays.

Barriers to listing for HIV-infected patients being evaluated for kidney transplantation.

Human immunodeficiency virus (HIV)-infected patients have excellent outcomes following kidney transplantation (KT) but still might face barriers in the evaluation and listing process. The aim of this study was to characterize the patient population, referral patterns, and outcomes of HIV-infected patients who present for KT evaluation. We performed a single-center retrospective cohort study of HIV-infected patients who were evaluated for KT. The primary outcome was time to determination of eligibility for KT. Between 2011 and 2015, 105 HIV-infected patients were evaluated for KT. Of the 105 patients, 73 were listed for transplantation by the end of the study period. For those who were deemed ineligible, the most common reasons cited were active substance abuse (n = 7, 22%) and failure to complete the full transplant evaluation (n = 7, 22%). Our cohort demonstrated a higher proportion of HIV-infected patients eligible for KT than in previous studies, likely secondary to advances in HIV management. Among those who were denied access to transplantation, we identified that many were unable to complete the evaluation process, and that active substance abuse was common. Future prospective studies should examine reasons and potential interventions for the lack of follow-through and drug use we observed in this population.

The use of history to identify anterior cruciate ligament injuries in the acute trauma setting: the 'LIMP index'.

OBJECTIVE: To identify the injury history features reported by patients with anterior cruciate ligament (ACL) injuries and determine whether history may be used to identify patients requiring follow-up appointments from acute trauma services. METHODS: Multisite cross-sectional service evaluation using a survey questionnaire design conducted in the UK. The four injury history features investigated were 'leg giving way at the time of injury', 'inability to continue activity immediately following injury', 'marked effusion' and 'pop (heard or felt) at the time of injury'(LIMP). RESULTS: 194 patients with ACL injury were identified, of which 165 (85.5%) attended an acute trauma service. Data on delay was available for 163 (98.8%) of these patients of which 120 (73.6%) had a follow-up appointment arranged. Patients who had a follow-up appointment arranged waited significantly less time for a correct diagnosis (geometric mean 29 vs 198 days; p<0.001) and to see a specialist consultant (geometric mean 61 vs 328 days; p<0.001). Using a referral threshold of any two of the four LIMP injury history features investigated, 95.8% of patients would have had a follow-up appointment arranged. CONCLUSIONS: Findings support the value of questioning patients on specific injury history features in identifying patients who may have suffered ACL injury. Using a threshold of two or more of the four LIMP history features investigated would have reduced the percentage of patients inappropriately discharged by 22.2%. Evidence presented suggests that this would significantly reduce the time to diagnosis and specialist consultation minimising the chance of secondary complications.

A Retrospective Review: Significance of Vegetation Size in Injection Drug Users with Right-Sided Infective Endocarditis.

BACKGROUND: Previously described prognostic markers in right-sided infective endocarditis (RSIE) include vegetation size ≥1cm, fever for more than three weeks, cardiac failure and severe sepsis. This study aimed to evaluate effectiveness of medical therapy for vegetations ≥1cm and explore determinants of outcome in a representative population of intravenous drug users (IDUs) at a metropolitan Australian health service. METHODS: Retrospective review of consecutive IDUs presenting to our institution with native-valve RSIE (by modified Duke criteria) over seven years (2005-2011). Data recorded included echocardiographic estimation of maximal vegetation diameter (classified as < or ≥1cm). Relationships between vegetation size and specified outcomes of death, septic shock, recurrence and relapse were examined by Chi-squared testing. RESULTS: Of 49 episodes five (10%) were managed surgically and a further four (8%) were lost to follow-up and excluded from the analysis. Of the remaining 40 evaluable medically treated patients (median age 28, range 20-55), 37 (93%) cultured methicillin-sensitive S. aureus and all had tricuspid valve involvement. Of 24 with vegetations ≥1cm, three died (mortality 13%) compared with one (6%) in 16 medically treated patients with vegetations <1cm (p=0.63). A Pittsburgh (PITT) bacteraemia score of ≥4 at presentation was associated with a mortality of 24% (four of 17 patients died) compared with 0 in 23 patients with PITT scores <4 (p=0.026). CONCLUSION: Medical therapy alone can be effective for RSIE when large vegetations are present. However a high sepsis score at presentation may increase risk of death. Larger studies are required to determine optimal indications for early surgical intervention.

Universal power law governing pedestrian interactions.

Human crowds often bear a striking resemblance to interacting particle systems, and this has prompted many researchers to describe pedestrian dynamics in terms of interaction forces and potential energies. The correct quantitative form of this interaction, however, has remained an open question. Here, we introduce a novel statistical-mechanical approach to directly measure the interaction energy between pedestrians. This analysis, when applied to a large collection of human motion data, reveals a simple power-law interaction that is based not on the physical separation between pedestrians but on their projected time to a potential future collision, and is therefore fundamentally anticipatory in nature. Remarkably, this simple law is able to describe human interactions across a wide variety of situations, speeds, and densities. We further show, through simulations, that the interaction law we identify is sufficient to reproduce many known crowd phenomena.

Late parastomal evisceration: A case report of a rare complication following loop ileostomy for an obstructing rectal cancer.

INTRODUCTION AND IMPORTANCE: Parastomal evisceration is a very uncommon complication of a stoma, with only a few cases currently published in the literature. It may occur either early or late following either ileostomy or colostomy and has been reported in both the emergency and elective setting. The aetiology is likely multifactorial, but a few risk factors have been identified that predispose to its occurrence. Early recognition and prompt surgical evaluation is necessary, and management depends on patient, pathologic and environmental factors. CASE PRESENTATION: A 50-year-old man with an obstructing rectal cancer underwent elective surgery for the creation of a temporary loop ileostomy prior to commencement of neoadjuvant chemotherapy (capecitabine and oxaliplatin). His background included obesity, alcohol excess and he was a current smoker. His postoperative course was complicated by a non-obstructing parastomal hernia which was managed non-operatively in the context of his neoadjuvant therapy. Seven months after his loop ileostomy and three days post his sixth cycle of chemotherapy, he presented to the emergency department with signs of shock and evisceration of small bowel via a dehiscence of the mucocutaneous junction at the superior aspect of the loop ileostomy. We discuss this unusual case of late parastomal evisceration. CLINICAL DISCUSSION: Parastomal evisceration is caused by a mucocutaneous dehiscence. Risk factors such as coughing, increased intra-abdominal pressure, emergency surgery, and stomal prolapse or hernia can all be predisposing factors. CONCLUSION: Parastomal evisceration is a life-threatening complication that requires urgent assessment, resuscitation, and early referral to the surgical team for intervention.

Doctor when can I drive? A systematic review and meta-analysis of return to driving after total hip arthroplasty.

BACKGROUND/OBJECTIVE: Advice given to patients on driving resumption after total hip arthroplasty (THA) is inconsistent. Due to a lack of clear guidelines, surgeons' recommendations range between 4-8 weeks after surgery to resume driving. Delays in driving return can have detrimental social and economic impact. However, it is important to ensure patients only resume driving once safe. This study presents a systematic review and meta-analysis of driving simulation studies after THA to establish when patients can safely return to driving postoperatively. METHODS: A systematic review and meta-analysis using PRISMA guidelines was undertaken. Titles and abstracts were screened for inclusion, data was extracted, and studies assessed for bias risk. Review Manager, was used for statistical analysis. Values for brake reaction time (BRT) were included for meta-analysis. RESULTS: 14 articles met the inclusion criteria. Of these, 7 measured BRT and were included in the meta-analysis. Pooled means of both right and left THA showed BRT around or above preoperative baseline at 1 week, 2 weeks and 3 weeks, and below baseline at 6 weeks, 12 weeks, 32 weeks and 52 weeks. Of these, the pooled means at 6, 32, and 52 weeks were significant (p < 0.05).Studies not meeting meta-analysis inclusion criteria were included in a qualitative analysis, examining self-reported postoperative driving return times which ranged from 6 days to over a year or in rare cases, never. Majority of patients (n = 960) self-reported driving return within approximately 6 weeks (pooling of mean values 32.9 days). CONCLUSIONS: The mean return to driving time recommended in the literature was 4.5 weeks. Based upon BRT meta-analysis, a return to baseline braking performance was noted at 6 weeks postoperatively. However, driving is a complex skill, and patient recommendation should be individualised based on factors such as vehicle transmission type, THA technique, surgical side, medication and comorbidities.

Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients.

PURPOSE: Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [(18) F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. METHODS: Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38°C and neutrophil count <500 cells/µl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. RESULTS: The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/µl (range 0-730 cells/µl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as "true positives" by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). CONCLUSION: This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required.