Standard-of-care antiretroviral therapy (ART) uses a combination of drugs deemed essential to minimise treatment failure and drug resistance. Protease inhibitors are potent, with a high genetic ...barrier to resistance, and have potential use as monotherapy after viral load suppression is achieved with combination treatment. We aimed to assess clinical risks and benefits of protease inhibitor monotherapy in long-term clinical use: in particular, the effect on drug resistance and future treatment options.
In this pragmatic, parallel-group, randomised, controlled, open-label, non-inferiority trial, we enrolled adults (≥18 years of age) positive for HIV attending 43 public sector treatment centres in the UK who had suppressed viral load (<50 copies per mL) for at least 24 weeks on combination ART with no change in the previous 12 weeks and a CD4 count of more than 100 cells per μL. Participants were randomly allocated (1:1) to maintain ongoing triple therapy (OT) or to switch to a strategy of physician-selected ritonavir-boosted protease inhibitor monotherapy (PI-mono); we recommended ritonavir (100 mg)-boosted darunavir (800 mg) once daily or ritonavir (100 mg)-boosted lopinavir (400 mg) twice daily, with prompt return to combination treatment if viral load rebounded. All treatments were oral. Randomisation was with permuted blocks of varying size and stratified by centre and baseline ART; we used a computer-generated, sequentially numbered randomisation list. The primary outcome was loss of future drug options, defined as new intermediate-level or high-level resistance to one or more drugs to which the patient's virus was deemed sensitive at trial entry (assessed at 3 years; non-inferiority margin of 10%). We estimated probability of rebound and resistance with Kaplan-Meier analysis. Analyses were by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN04857074.
Between Nov 4, 2008, and July 28, 2010, we randomly allocated 587 participants to OT (291) or PI-mono (296). At 3 years, one or more future drug options had been lost in two participants (Kaplan-Meier estimate 0·7%) in the OT group and six (2·1%) in the PI-mono group: difference 1·4% (−0·4 to 3·4); non-inferiority shown. 49 (16·8%) participants in the OT group and 65 (22·0%) in the PI-mono group had grade 3 or 4 clinical adverse events (difference 5·1% 95% CI −1·3 to 11·5; p=0·12); 45 (six treatment related) and 56 (three treatment related) had serious adverse events.
Protease inhibitor monotherapy, with regular viral load monitoring and prompt reintroduction of combination treatment for rebound, preserved future treatment options and did not change overall clinical outcomes or frequency of toxic effects. Protease inhibitor monotherapy is an acceptable alternative for long-term clinical management of HIV infection.
National Institute for Health Research.
Purpose There has not been a broad national examination of complications and demographics of facial trauma reduction procedures. The literature has reported acceptable and unacceptable hardware ...removal rates in localized populations. Materials and Methods The 2007 Nationwide Inpatient Sample was used to determine all plate removal procedures associated with common complications from facial reductions. Statistical analysis was used to compare the differences in demographics of the reduction procedure and removal procedure groups. Results Some form of open fixation was reported in 4,879 patients. Plate removals associated with complications were reported in 246 patients. The “failure” removal rate as a percentage of the total number of open procedures for the year was 5.0%. Gender, race, age, primary payer, and median income of the patient were determined to significantly affect the likelihood for hardware removal due to complications. Conclusion These results suggest that decreased lower bone quality and ability to pay affect the chances that a particular patient will undergo a hardware removal procedure. There is a strong possibility that the reported removal rate underestimates the actual failure rate of the procedures and devices used to treat facial trauma.
Summary Idiopathic recurrent pericarditis (IRP) impairs quality of life. Although its precise etiology is not certain, it is believed to be immunologically mediated. Its optimal treatments are ...unknown. Initial therapy is with non-steroidal anti-inflammatory drugs and colchicine. Steroids, which are often used, however may promote recurrences. European guidelines advocate azathioprine or cyclophosphamide in refractory cases despite limited evidence. We report two adults with IRP successfully treated with the interleukin-1 antagonist, anakinra. We combine this experience with the first systematic literature review of immunosuppression in IRP. A total of 8 papers were included in the review, which alongside our patients described 18 cases. The best treatments comprised anakinra and intravenous immunoglobulin, with respective remission rates of 100% and 67%. Cyclophosphamide and azathioprine were less efficacious. The unprovoked inflammatory episodes in our patients alongside their prompt response to anakinra indicate that in some instances IRP may represent an autoinflammatory condition. We suggest that in IRP refractory to initial treatment, anakinra should be considered as a potential therapy. Clinical trials are required to confirm its benefits in IRP.
Abstract Study Objective To describe how pediatric and adolescent patients present to the gynecologist when they have tethered cord syndrome (TCS). Design We conducted a retrospective chart review on ...all patients suspected by the gynecologist of having TCS. Setting Single pediatric and adolescent gynecology clinic in a mid-sized city in the midwest. Participants Thirty-two patients, first seen between 2005 and 2012, suspected of having TCS and for whom follow-up information was available. Interventions and Main Outcome Measures Patient characteristics, including patient history, gynecologic clinical indicators, clinical outcomes, indications for surgery, and postoperative resolution of symptoms, were reviewed. Results The initial review of systems indicated stress urinary incontinence, back pain, and constipation as common markers in the 32 patients who were suspected of having TCS. All 32 patients underwent lumbar magnetic resonance imaging without contrast and evaluation by neurosurgery. Of the 32 patients with suspected TCS, 18 were later confirmed and 14 were shown to not have TCS. Of the 18 patients with sufficient information to justify a detethering procedure, 14 patients were followed and 93% (13 patients) had complete resolution of symptoms. Final diagnosis in the non-TCS group varied, including vulvovaginitis, enuresis, chronic constipation, and lichen sclerosis. Symptoms improved with the treatment of each primary condition. Conclusions TCS symptoms overlap with gynecologic conditions; therefore, patients with TCS may present initially to the gynecologist. In pediatric/adolescent patients, TCS should be considered when stress urinary incontinence, back pain, and constipation are discovered in the review of systems. Because possible irreversible ischemic and neurologic changes are believed to be involved, early diagnosis and surgery are crucial for resolution. Providers should be aware of TCS in these pediatric and adolescent settings, because quick assessment may result in complete resolution of a chronic progressive disease.
Objectives To analyze data from the Scottish capillary thyroid stimulating hormone (TSH) screening program for hypothyroidism in Down syndrome to identify a threshold for capillary TSH elevation ...below which low venous free thyroxine (fT4) (<9 pmol/L) and/or frank venous TSH elevation (>10 mU/L) range is unlikely. Study design Review of proformas prospectively submitted on all children with Down syndrome referred via the screening program between 2003 and 2013. Results Ninety-nine patients with Down syndrome (50 females, 49 males) were identified, 76 school-age (≥5 years) and 23 preschool (<5 years), mean (range) age at referral 9.4 (0.9-18.1) years. Pearson correlation between capillary TSH and venous TSH was 0.814; between capillary TSH and venous fT4 −0.522 ( P = .01). Receiver operator curve analysis showed that capillary TSH values of 4 and 6 mU/L were 95.9% and 73.5% sensitive, 5.8% and 80.8% specific, respectively, in predicting venous TSH >10 mU/L. Fifty-three children had capillary TSH values of 4-5.9 mU/L of whom only one, a boy of 15.8 years, had subnormal venous fT4 (<9 pmol/L), and venous TSH >10 mU/L was found in 13 (4 preschool). Conclusions Venous fT4 is normal in almost all patients with Down syndrome with capillary TSH 4-6 mU/L. We propose an algorithm incorporating rescreening by finger prick after 6 months, rather than venepuncture, in school-aged children with borderline capillary TSH elevation. Further data are needed before this approach can be recommended for preschool children.
To determine how first-year medical students interested in rural family medicine in Canada differ from their peers.
From 2002 to 2004, first-year students (n = 2189) from 16 classes in 8 Canadian ...medical schools ranked intended career choices and indicated influences on their choices using Likert scales. We used t tests and chi2 tests to determine demographic influences and factor analysis, and we used analysis of variance to examine associated attitudes.
Of the 1978 surveys returned (90.3%), 1905 were used in the analysis. Rural family medicine was ranked first by 11.1%, varying from 4.7% to 20.2% among schools. Students interested in rural family medicine were more likely to have grown up rurally, graduated from a rural high school and have family in a rural location than others (p < 0.001). They were more likely to be older, in a relationship, to have volunteered in a developing nation and less likely to have university-educated parents than those interested in a specialty (p < 0.008). Attitudes of students choosing family medicine, rural or urban, include social orientation, preference for a varied scope of practice and less of a hospital orientation or interest in prestige, compared with students interested in specialties (p < 0.001).
Medical schools may address the rural physician shortages by considering student demographic factors and attitudes at admission.
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