Clinical characteristics of women with HIV in the RESPOND cohort: A descriptive analysis and comparison to men.

BACKGROUND: Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS: RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS: Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/µl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/µL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION: RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.

Inverted-Bearing Reverse Shoulder Arthroplasty: Long-term Survivorship, Complications, Clinical and Radiological Outcomes.

BACKGROUND: Inverted-bearing reverse shoulder arthroplasty (IB-RSA) is characterized by a polyethylene glenosphere and a metallic humeral liner to minimize PE wear and debris secondary to impingement between the humerus and glenoid neck. IB-RSA long-term survivorship, complication and revision rates, as well as clinical and radiographic outcomes have not been reported yet. METHODS: This is a monocentric retrospective study on a consecutive series of 151 patients who underwent primary IB-RSA from January 2009 to September 2015 and were evaluated clinically and radiologically at minimum 8 years follow-up. All complications and reoperations were recorded. Survivorship analysis with any revision surgery as endpoint was done using Kaplan-Meier survival curves. RESULTS: Seventy-eight patients (follow-up rate 51.7%) were reviewed at a mean follow-up of 10.1 ± 1.9 years. At 10 years the revision-free survival was 98.7% (95% CI: 94.8-99.7). Sixteen complications (10.6%) were observed: 2 axillary nerve injuries, 2 infections, 2 glenoid loosenings (which stabilized within one year), 2 cases of otherwise unexplained painful stiffness, 4 acromial fractures, 1 post-traumatic scapular pillar fracture and 3 post-traumatic humeral periprosthetic fractures. Two patients were revised due to infection. No cases of late glenoid loosening and humeral loosening were observed. The revision rate was 1.3%. All the clinical scores and range of motion significantly improved at the last follow-up compared with preoperative status: final Constant score was 66.1 ± 17.4, SSV 79.1 ± 20.9, ASES 82.2 ± 17.7. Scapular notching was observed in 51.4% of patients: only 1 case of grade 3 notching was observed in an early glenoid subsidence case. CONCLUSIONS: Primary IB-RSA appears to be a safe and effective procedure and does not present specific implant-associated complications at long-term follow-up. Radiographic analysis showed that inverting the biomaterials leads to a distinct kind of notching with mainly mechanical features.

Did the first description of patients with polymyalgia rheumatica take place in Scotland or in Denmark?

The first description of polymyalgia rheumatica (PMR) is generally attributed to Dr. Bruce. In an 1888 article entitled Senile rheumatic gout, he described five male patients aged from 60 to 74 years whom he had visited at the Strathpeffer spa in Scotland. In 1945, Dr. Holst and Dr. Johansen reported on five female patients examined over several months at the Medical Department of Roskilde County Hospital in Denmark. These patients suffered from hip, upper arms, and neck pain associated with elevated ESR and constitutional manifestations such as low-grade fever or loss of weight. In the same year, Meulengracht, another Danish physician, reported on two patients with shoulder pain and stiffness associated with fever, weight loss, and an increased erythrocyte sedimentation rate. As in the five patients reported by Dr. Holst and Dr. Johansen, a prolonged recovery time was recorded. On reading and comparing these three accounts, we question whether it is correct to attribute the first description of PMR to Dr. Bruce and put forward shifting this accolade to the three Danish physicians.

Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

Long-term stability of coracoclavicular suture fixation for acute acromioclavicular joint separation.

PURPOSE: The optimal (SBJI) surgical treatment for acute acromioclavicular (AC) joint disruption remains controversial. What is being presented is the long-term functional outcomes of a double cross-looped coracoclavicular (CC) suture technique with the intention of restoring both anteroposterior and superior displacement of the clavicle. METHODS: Between 2007 and 2016, 81 patients underwent surgical reconstruction for acute acromioclavicular joint (AC) disruption in two orthopaedic centers. Two patients died for reasons unrelated to the treatment, and seven missed the final follow-up appointment, leaving 72 patients (67 males; 5 females; age 37 ± 12.4; range 15-64 years) for clinical and radiological assessments. All cases were classified according to the Rockwood classification as type III (n = 34), IV (n = 14) or V (n = 24). The dislocation was repaired with double cross-looped CC fixation using four Ethibond sutures passing underneath the coracoid and through a 4.5 mm drill hole in the clavicle in opposing directions to control both anteroposterior and vertical displacement. Radiological investigation preoperatively and at the last follow-up included anteroposterior and/or Zanca views, axillary or Alexander views, and comparative stress radiography of both AC joints. Patients were evaluated clinically with the Constant-Murley score (CMS) and Acromio Clavicular Joint Instability Score (ACJIS). Loss of reduction, subluxation, CC ligament ossification, post-traumatic arthritis, and peri-implant fractures were also recorded. RESULTS: Seventy-two patients were available for the last clinical and radiological evaluations. At a median follow-up period of 6.3 ± 2.1 years (range 3-12 years), the CMS and ACJIS were 92.1 ± 7.2 (range 60-100 points) and 90.4 ± 8.6 (range 45-100 points), respectively. Complications included 9 (12.5%) patients with slight loss of reduction, 2 (1.7%) with dislocation recurrence, 1 (1.3%) with superficial infection, 1 (1.3%) with a fracture of the lateral end of the clavicle, and 2 (1.7%) with persistent tenderness in the AC joint. The incidence of periarticular ossification was 22.4% and did not affect the final outcome. CONCLUSIONS: This technique represents an effective and low-cost treatment for acute AC joint separations. LEVEL OF EVIDENCE: IV.

Rilpivirine plus cobicistat-boosted darunavir as a two-drug switch regimen in HIV-infected, virologically suppressed subjects on steady standard three-drug therapy: a randomized, controlled, non-inferiority trial (PROBE 2).

BACKGROUND: We explored the combination of rilpivirine plus cobicistat-boosted darunavir [a two-drug regimen (2DR)] when switching from standard triple combined ART. METHODS: In this randomized, open-label, non-inferiority trial, participants had an HIV-RNA <50 copies/mL on a stable (>6 months) three-drug regimen. The primary endpoint was proportion with HIV-RNA <50 copies/mL at Week 24 (snapshot algorithm), with a -12% non-inferiority margin. ClinicalTrials.gov: NCT04064632. RESULTS: One hundred and sixty patients were allocated (1:1) to 2DR or to continue current ART (CAR). At Week 24, 72 (90.0%) of participants with 2DR and 75 (93.8%) with CAR maintained HIV-RNA <50 copies/mL [difference -3.75% (95% CI = -11.63 to 5.63)], confirming non-inferiority. Non-inferiority was confirmed considering an HIV-RNA >50 copies/mL (0% for 2DR; 3.7% for CAR; 95% CI = -0.4 to 7.9). Four patients reported adverse events not leading to treatment discontinuation (one patient in the 2DR group and three patients in the CAR group); eight subjects discontinued therapy in the 2DR group and three in the CAR group. With 2DR, lipid serum concentrations increased, but differences were statistically significant only for tenofovir disoproxil fumarate-containing CAR and in 2DR patients receiving a pre-switch regimen including tenofovir disoproxil fumarate. Median bone stiffness decreased in the CAR group from 86.1 g/cm2 (IQR = 74-98) to 83.2 g/cm2 (IQR = 74-97) and increased in the 2DR group from 84.9 g/cm2 (IQR = 74-103) to 85.5 g/cm2 (IQR = 74-101). The reduction within the CAR group was significant (P = 0.043). CONCLUSIONS: Once-daily rilpivirine plus cobicistat-boosted darunavir is an effective 2DR that combines a high virological efficacy with a potential to avoid major NRTI toxicities.

Treatment outcomes of integrase inhibitors, boosted protease inhibitors and nonnucleoside reverse transcriptase inhibitors in antiretroviral-naïve persons starting treatment.

OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

Arthroscopic transosseous versus suture anchor repair: clinical outcomes in patients with bilateral rotator cuff tears.

The aim of our study was to define if Arthroscopic Transosseous Rotator Cuff Techniques should have comparable results to those of the suture-anchors technique in a single row configuration. We reported the preliminary results of a consecutive population of 22 patients who underwent a rotator cuff treatment on the left and right sides for average medium-sized thickness tears with minimal fatty infiltration with the two different techniques: transosseous rotator cuff repair technique on one side and single row with suture-anchors on the other side, in different times. Subjective evaluation with DASH questionnaires, Constant Scores and Numerical Rating Scale (NRS) for pain evaluation, have been submitted pre and postoperatively after both operations. A statistical analysis was performed to assess the superiority of one technique and to compare pre and postoperative ROM data and clinical outcomes. A transosseous rotator cuff repair was performed in 7 patients on the dominant arm, while the other 15 patients had dominant arm cuff tear lesions repaired by using suture-anchors technique. At last follow-up a significant improvement, in shoulder pain and function, was referred at both sides. Also, DASH, Constant Scores and NRS for pain evaluation improved with both techniques, but no statistical difference was found between them. Arthroscopic transosseous rotator cuff repair technique shows comparable results to those of the suture-anchors technique in a single row configuration.

Do radiolucent lines and stress shielding of the humeral shaft really matter in shoulder arthroplasty?

The purpose of this study is to evaluate at a mid-term follow up, the radiological survival of an uncemented humeral stem in shoulder arthroplasty. One hundred and twenty-six replacements including hemi (HA), total (TSA) and reverse (RSA) implanted from 1999 to 2008 were reviewed at a mean follow up of 7.2 years (48-144 months). The same uncemented triconical stem (SMR, Lima Corporate) was implanted. There were: 23 HSA, 43 TSA, 60 RSA. An independent observer evaluated all the patients with Constant Score. A radiologic analysis by an expert radiologist and an orthopaedic surgeon was performed: humeral component-bone interface was divided in seven zones. They judged a mobilisation if a migration or tilt of the humeral implant or if≥ 2 mm radiolucent line in at least three zones was present. Chi-squared test, Fisher test and analysis of variance were performed and a p<0.05 was considered statistically significant. No major radiological signs of loosening and no tilt or migration of the humeral component were found. Only 23 (18.2%) patients had no RL around the humeral implant. In the remaining 103 (81.7%) implants: 96 (76.1%) presented RL less than 2 mm, particularly 75 (59.5%) in less than 3 zones and 21 (16.6%) in more than 3 zones. Of the remaining 7 (5.5%) implants the presence of RL of 2 mm or greater in only one zone was seen. Apart from sepsis no revision was performed for humeral component loosening. Although a high rate of RL, uncemented humeral stem has an excellent survivorship at a mid-term follow up. Relationship between presence, position and depth of RL and internal stress shielding is commonly observed but does not appear to compromise quality of fixation or clinical outcomes in shoulder arthroplasty.

Rapid initiation of antiretroviral therapy at HIV diagnosis: definition, process, knowledge gaps.

Initiating antiretroviral therapy (ART) as early as the day of HIV diagnosis is a strategy of increasing global interest to control the HIV epidemic and optimize the health of people living with HIV (PLWH). No detrimental effects of rapid-start ART have been identified in randomized controlled trials undertaken in low- or middle-income countries, or in cohort studies performed in high-income countries. Rapid-start ART may be a key approach in reaching the 2020 Joint United Nations Programme on HIV/AIDS goal of 90% of all PLWH knowing their status, 90% of those diagnosed receiving sustained ART, and 90% of those receiving ART achieving viral suppression; it may also be important for achieving the suggested fourth "90%" goal: improving health-related quality-of-life in PLWH. Presently there is insufficient broad evidence for guidelines to recommend universal test-and-treat strategies for all people, in all settings, at HIV diagnosis; consequently, there is a pressing need to conduct high-quality studies that investigate immediate ART initiation. This article evaluates global evidence regarding rapid-start ART, including same-day start, with particular focus on the implementation of this strategy in high-income countries.

Evolution of major non-HIV-related comorbidities in HIV-infected patients in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) Foundation Study cohort in the period 2004-2014.

OBJECTIVES: The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004-2014. METHODS: Analyses were conducted separately for a closed cohort (same people seen at both times) and an open cohort (all people under follow-up). We used the χ2 test for categorical factors and the Wilcoxon test for quantitative factors to compare profiles over time. RESULTS: The closed cohort included 1517 participants and the open cohort 3668 under follow-up in 2004 and 6679 in 2014. The median age of the open cohort was 41 [interquartile range (IQR) 37-46] years in 2004 and 44 (IQR 36-52) years in 2014. Analysis of the closed cohort showed an increase in the prevalence of some NCDs [the prevalence of dyslipidaemia increased from 75% in 2004 to 91% in 2014, that of hypertension from 67 to 84%, and that of cardiovascular disease (CVD) from 18 to 32%] and a decrease in renal function (5% with eGFR < 60 mL/min per 1.73 m2 in 2004 versus 30% in 2014); the percentage of people in the high-risk group for the Framingham CHD score more than tripled (from 13 to 45%). Results in the open cohort were similar. CONCLUSIONS: The burden of NCDs in our PLWHIV population markedly worsened over a 10-year time-span, which is likely to be a result of the effects of both ageing and HIV infection as well as their interaction. Special attention must be given to the management and prevention of NCDs.

Arthroscopic anatomic repair of Bankart lesion in rugby players.

Recent studies have reported equivalent outcomes of arthroscopic and open shoulder stabilization. However, surgical strategy for shoulder instability is a challenging and controversial problem for surgeons that have to treat collision sport athletes. In fact, only few studies support the arthroscopic surgery for this group of patients. The aim of this study is to evaluate the outcome of arthroscopic stabilization in a homogenous population of professional young athletes practicing in high-level collision sport. We treated 22 consecutive professional rugby players, with a mean age of 23.6 years, affected by traumatic anterior shoulder instability. All patients underwent arthroscopic Bankart repair with bone suture-anchors. Exclusion criteria were: failed previous shoulder surgery, atraumatic, multidirectional or posterior instability, bone defects greater than 20% of the anterior-inferior glenoid, engaging Hill-Sachs, rotator cuff tears, capsular-ligament avulsion on the humeral side (HAGL). Patients were evaluated according to Constant score, Rowe score and Visual Analogue Scale (VAS) for discomfort and handicap. The mean follow-up was 40.7 months (range, 6 to 87 months). All patients except one were able to return at the same previous sports level at 5 to 6 months postoperatively. Re-dislocation occurred in 3 players for high impact trauma during competition or training. Our results confirm that, also in the collision sport patients, anatomic arthroscopic Bankart repair is a good option for the treatment of traumatic anterior instability without associated lesions. .

Rotator cuff degeneration of the healthy shoulder in patients with unilateral arm amputation is not worsened by overuse.

PURPOSE: In order to evaluate whether overuse has a significant role in rotator cuff tear (RCT) aetiology, we evaluated both shoulders of patients with old unilateral arm amputation expecting a higher rate of RC degeneration in the healthy side. METHODS: Nineteen males and six females (mean age: 57.3 ± 10.1) with an old (>20 years) unilateral arm amputation were submitted to an MRI of both shoulders. Tendon status and muscle tropism were evaluated according to Sugaya and Fuchs classifications, respectively; the acromion humeral distance was measured. Statistical analysis was performed to verify the prevalence of Sugaya and Fuchs categories in each sides. RESULTS: A significant prevalence of Sugaya type II in the amputated side (p = 0.02) and of type I in the healthy side (p < 0.001) was found. Rotator cuff was healthy in 28 and 52% of amputated and non-amputated side, respectively. The mean acromio-humeral distances of the amputated and healthy side were 0.8 cm (SD: 0.1) and 0.9 cm (SD: 0.1), respectively, (p = 0.02). A significant prevalence of Fuchs type II category in the healthy side (p < 0.001) was found. Fuchs III/IV were observed in 40 and 12% of amputated and healthy side, respectively. CONCLUSIONS: The present study resizes the role of overuse on the aetiology of RCT. Cuff tear prevalence in not amputated shoulders, inevitably submitted to functional overload, was not higher than that of coetaneous subjects with two functional upper limbs. Shoulder non-use is a risk factor for rotator cuff tear. As the prevalence of rotator cuff degeneration/tear is higher in the amputee side, non-use is a more relevant risk factor than overuse. In the daily clinical practice, patients with rotator cuff tear should be encouraged to shoulder movement because rotator cuff tendon status could be worsened by disuse. LEVEL OF EVIDENCE: III.

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. RESULTS: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. CONCLUSIONS: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

Infection-related and -unrelated malignancies, HIV and the aging population.

OBJECTIVES: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. METHODS: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. RESULTS: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/µL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/µL], independent of age, while a CD4 count < 200 cells/µL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40-4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5-5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2-7.2) per 1000 person-years over the same period. CONCLUSIONS: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost-benefit of screening for IURMs in HIV-infected populations.

Early rehabilitation vs. conventional immobilization in nonoperative treatment of proximal humeral fracture: a systematic review.

OBJECTIVE: Fractures of the proximal humerus (PHF) are commonly treated conservatively. Evidence suggests that a period of immobilization of one week or less may lead to some advantages compared to a traditional 3-4 weeks of immobilization. The purpose of this systematic review was to assess the clinical and radiological results in the case of early rehabilitation vs. delayed rehabilitation after PHF. MATERIALS AND METHODS: In July 2023, a literature search was carried out on the PubMed, MEDLINE, and Embase databases to identify all the randomized trials comparing early rehabilitation vs. delayed rehabilitation after PHF. The following data were extracted from each included study: patients' demographics, study design and level of evidence, follow-up times, treatment groups, evaluation scores adopted, and overall clinical and radiological findings. The quality of the trials was assessed using the Cochrane Risk of Bias Assessment. RESULTS: A total of 5 studies, including 378 patients and dealing with early vs. delayed rehabilitation in case of conservative treatment of PHF, were included in this study. Early rehabilitation was started within 1 week and consisted mainly of pendulum exercise and progressive passive mobilization. Early rehabilitation was associated with better pain and functional scores within the first 3 months in 3 studies. No difference in pain or function was reported at 6 months or longer follow-up, and no differences in complications rate were observed between early vs. delayed rehabilitation groups. CONCLUSIONS: This systematic review suggests that early mobilization within one week in case of conservative treatment of PHF leads to improved function recovery and reduced pain, especially in the first months of rehabilitation, without differences at longer follow-up and without increasing complications rate. Reducing immobilization time could accelerate function recovery and regaining independence in daily life activities.

The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/µL in the post-combination antiretroviral therapy era.

BACKGROUND: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. METHODS: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. RESULTS: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL. DISCUSSION: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Number of daily pills, dosing schedule, self-reported adherence and health status in 2010: a large cross-sectional study of HIV-infected patients on antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess whether pill burden is associated with self-reported adherence to current combination antiretroviral regimens and health status in a large sample of unselected and chronically treated HIV-infected patients. METHODS: An adherence and health status questionnaire was offered to all patients collecting their drugs between March and May 2010 at our clinic; both parameters were primarily evaluated using a visual analogue scale. Linear correlations were evaluated using Spearman's correlation coefficient. Wilcoxon's rank-sum test and the χ(2) test were used to compare quantitative and qualitative variables. The generalized linear model was used in multivariable analyses. RESULTS: Among 2763 subjects on treatment during the study period, 2114 (78.8% male; mean age 46.9 ± 8.84 years) were tested for adherence; 1803 (85.3%) had viral loads < 50 HIV-1 RNA copies/mL. After adjusting for age, gender, HIV risk factor, current CD4 count, pill burden and dosing interval, adherence was higher in patients with undetectable HIV RNA (P < 0.0001) and directly associated with current CD4 count (P = 0.029). After adjusting for the same variables, health status was better in patients with undetectable viraemia (P = 0.004) and in men who have sex with men (MSM) and heterosexuals compared with injecting drug users and those with other risk factors (P < 0.0001 for MSM and P = 0.008 for heterosexuals); it was also directly associated with current CD4 count (P < 0.0001) and inversely associated with age (P < 0.0001) and pill burden (P = 0.019). CONCLUSIONS: In this highly adherent population, the number of daily pills was related to self-reported health status but not to self-reported adherence, whereas the dosing interval did not influence self-reported adherence or health status.