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explain why HIVST kits, without peer navigators support, did not create demand for PrEP.

Both professional (peer navigators) and social network (friends) approaches were acceptable methods to receive HIVST and sexual health information. Doubts about the professionalism of friends and overly exclusive focus on HIVST information materials may in part explain why HIVST kits, without peer navigators support, did not create demand for PrEP.

This study aimed to assess the knowledge, attitude and practice (KAP) among community-dwelling adults in Malaysia regarding advance care planning (ACP), and its associated factors.

This cross-sectional study was conducted from July-September 2018.

This study was conducted at the University Malaya Medical Centre, Kuala Lumpur, Malaysia.

We recruited community-dwelling adults (ambulatory care patients or their accompanying persons) who were ≥21 years old and able to understand English or Malay. A 110 systematic sampling procedure was used. Excluded were community-dwelling adults with intellectual disabilities or non-Malaysian accompanying persons. A trained researcher administered the validated English or Malay Advance Care Planning Questionnaire at baseline and 2 weeks later.

The primary outcome was the KAP regarding ACP. The secondary outcomes were factors associated with KAP.

A total of 385/393 community-dwelling adults agreed to participate (response rate 98%). Only 3.1% of the community-dwellinACP, majority of community-dwelling adults in Malaysia had a positive attitude towards ACP and were willing to engage in a discussion regarding ACP after the term 'ACP' has been explained to them.

To investigate the relationship among baseline health-related quality of life (HRQoL), early changes in HRQoL from baseline to completion of the first cycle of chemotherapy, and prognosis in patients with advanced lung cancer.

This was a prospective, observational study.

The study was conducted in a national cancer centre in South China.

A total of 243 patients with chemo-naïve with advanced lung cancer were enrolled.

None.

The Functional Assessment of Cancer Therapy-Lung was used to assess HRQoL at baseline and at the end of the first cycle of chemotherapy. The Trial Outcome Index (TOI) and Lung Cancer Scale (LCS) were calculated as predictive indicators. Response to treatment was evaluated as per the Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1. Survival data were gathered from follow-up to September 2019.

Patients with 5-point or greater decreases in TOI (65% vs 48%, adjusted risk ratio (aRR)=2.19, 95% CI 1.09 to 4.41) or 2-point or greater decreases in LCS (72% vs 48%, aRR=3.29, 95% CI 1.50 to 7.22) from baseline to completion of the first cycle of chemotherapy were more likely to show stable or progressive disease than those whose HRQoL had improved. Baseline TOI ≤54 (80.0% vs 69.9%, adjusted hazard risk (aHR)=1.36, 95% CI 1.01 to 1.84) and LCS ≤21 (77.6% vs 72.5%, aHR=1.36, 95% CI 1.01 to 1.83) were associated with higher risk for death compared with TOI>54 and LCS>21. Area under the curve analysis indicated that early changes in LCS and baseline LCS scores could better predict response to treatment and overall survival than the corresponding TOI values.

Higher pretreatment HRQoL scores could predict longer survival, while declining HRQoL values could predict unfavourable treatment outcome among patients with advanced lung cancer. The use of the LCS is recommended for the routine collection of patient-reported HRQoL.

NCT01914120.

NCT01914120.

Small cell lung cancer (SCLC) is an aggressive disease with an overall 5-year survival rate of less than 10%. Treatment for SCLC with cisplatin/etoposide chemotherapy (C/E) ± radiotherapy has changed modestly over several decades. The ubiquitin-proteasome system is an underexplored therapeutic target for SCLC. We preclinically evaluated TAK-243, a first-in-class small molecule E1 inhibitor against UBA1.

We assessed TAK-243 in 26 SCLC cell-lines as monotherapy and combined with C/E, the PARP-inhibitor, olaparib, and with radiation using cell viability assays. We interrogated TAK-243 response with gene expression to identify candidate biomarkers. We evaluated TAK-243 alone and in combination with olaparib or radiotherapy with SCLC patient-derived xenografts (PDX).

Most SCLC cell lines were sensitive to TAK-243 monotherapy (EC50 median 15.8 nmol/L; range 10.2 nmol/L-367.3 nmol/L). TAK-243 sensitivity was associated with gene-sets involving the cell cycle, DNA and chromatin organization, and DNA damage reparapeutic strategy to improve SCLC patient outcomes, both as a single agent and in combination with existing therapies.

Praluzatamab ravtansine (CX-2009) is a conditionally activated Probody drug conjugate (PDC) comprising an anti-CD166 mAb conjugated to DM4, with a protease-cleavable linker and a peptide mask that limits target engagement in normal tissue and circulation. The tumor microenvironment is enriched for proteases capable of cleaving the linker, thereby releasing the mask, allowing for localized binding of CX-2009 to CD166. CX-2009 was evaluated in a phase I/II clinical trial for patients with advanced solid tumors.

Eligible patients had metastatic cancer receiving ≥2 prior treatments. CX-2009 was administered at escalating doses every 3 weeks (0.25-10 mg/kg) or every 2 weeks (4-6 mg/kg). Primary objective was to determine the safety profile and recommended phase II dose (RP2D).

Of 99 patients enrolled, the most prevalent subtype was breast cancer (n = 45). Median number of prior therapies was 5 (range, 1-19). Dose-limiting toxicities were observed at 8 mg/kg every 3 weeks and 6 mg/kg every 2 weeks. On the basis of tolerability, the RP2D was 7 mg/kg every 3 weeks. Tumor regressions were observed at doses ≥4 mg/kg. In the hormone receptor-positive/HER2-nonamplified breast cancer subset (n = 22), 2 patients (9%) had confirmed partial responses, and 10 patients (45%) had stable disease. Imaging with zirconium-labeled CX-2009 confirmed uptake in tumor lesions and shielding of major organs. Activated, unmasked CX-2009 was measurable in 18 of 22 posttreatment biopsies.

CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody-drug conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types.

CD166 is a novel, ubiquitously expressed target. CX-2009 is the first conditionally activated antibody-drug conjugate to CD166 to demonstrate both translational and clinical activity in a variety of tumor types.

Tyrosine kinase inhibitors (TKI) have poor efficacy in patients with glioblastoma (GBM). Here, we studied whether this is predominantly due to restricted blood-brain barrier penetration or more to biological characteristics of GBM.

Tumor drug concentrations of the TKI sunitinib after 2 weeks of preoperative treatment was determined in 5 patients with GBM and compared with its in vitro inhibitory concentration (IC50) in GBM cell lines. In addition, phosphotyrosine (pTyr)-directed mass spectrometry (MS)-based proteomics was performed to evaluate sunitinib-treated versus control GBM tumors.

The median tumor sunitinib concentration of 1.9 μmol/L (range 1.0-3.4) was 10-fold higher than in concurrent plasma, but three times lower than sunitinib IC50s in GBM cell lines (median 5.4 μmol/L, 3.0-8.5; P = 0.01). pTyr-phosphoproteomic profiles of tumor samples from 4 sunitinib-treated versus 7 control patients revealed 108 significantly up- and 23 downregulated (P < 0.05) phosphopeptides for sunitinib treatment,entrations might improve clinical benefit for patients with GBM. In parallel, a complex profile of kinase activity in GBM was found, supporting the potential of (phospho)proteomic analysis for the identification of targets for (combination) treatment.

EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer.

This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to part 1 (122), no treatment (control), trastuzumab or lapatinib; part 2 (112) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects.

Between November 2010 and September 2015, 257 patients were randomized (part 1 control 22, trastuzumab 57, lapatinib 51; part 2 control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab (P = 0.007) and 1/22 (5%) control (P < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab (P = 0.02) and 2/28 (7%) control (P < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences (P = 0.002).

Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.

Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation.

Based at a busy city hospital, the alcohol care team is a drug and alcohol specialist service, taking referrals for a wide range of patients with substance use disorders (SUD).

Patients with SUD are at high risk of vitamin D deficiency; this relates to frequent fractures and proximal myopathy. The coronavirus pandemic brought vitamin D into focus. Local guidelines advise that patients at high risk of vitamin D deficiency are offered replacement. Volasertib manufacturer There were no local data on vitamin D deficiency prevalence or any mention of patients with SUD in local vitamin D guidelines. The main aim of this project was to offer vitamin D checks and replacement to all appropriate patients.

We collected data on 207 patients, [pilot study (n=50) and two subsequent samples (n=95 and n=62)]. Our pilot study showed that no patients were offered vitamin D testing or replacement. We then offered vitamin D checks to 95 patients. Most had low vitamin D (30 patients were vitamin D deficient and 26 were vitamin D insufficient). We guidelines should add SUD as a risk factor for vitamin D deficiency. Hospital admission provides a rich opportunity to offer this simple intervention to patients who are often poorly engaged with community services.

Life expectancy (LE) depends on the wider determinants of health, which have different impact in women and men. Therefore, this study aimed to investigate whether gender equality was correlated with LE in women and men.

Gender equality in the 27 European Union (EU) member states between 2010 and 2019 was estimated using a modified Gender Equality Index (mGEI), based on the index developed by the European Institute for Gender Equality. The correlation between this mGEI and LE and the gender gap in LE was calculated using the Spearman correlation coefficient.

Between 2010 and 2019, LE increased more for men than women, which resulted in a narrowing of the gender gap in LE in the EU. During the same period, there was an increase in gender equality, as measured by the mGEI, although with substantial heterogeneity between countries. There was a strong correlation between the mGEI and the gender gap in LE (-0.880), which was explained by a stronger correlation between the mGEI and longer LE in men than in women (0.