Gender Differences In Treatment Outcomes Research Articles

A systematic review of sex and gender differences in treatment outcome of inflammatory skin diseases: Is it time for new guidelines?

Gender- and sex-specific differences in medicine were long-time disregarded. Despite numerous indications of gender- and sex-specific influences on the treatment of dermatological conditions, these have not yet been systematically investigated. To meet this unmet need, we conducted the present systematic review on the topic of gender and sex differences in the treatement outcome of skin diseases. Embase (via Ovid), PubMed Medline and Web of Science were searched, in between January 2001 and December 2022. English and german randomized controlled trials, prospective and retrospective cohorts and case-control studies that examined differences between men and women in treatment outcomes of skin diseases were included. Two authors independently screened the reports for eligibility, one extracted all data (the second double-checked) and critically appraised the quality and risk of bias of the studies. Eighty-three reports were included. The largest share of the identified publications focused on gender differences in psoriasis and psoriatic arthritis (n = 49), followed by melanoma (n = 8) and sporadic studies (n < 5) of inflammatory, infectious and autoimmune skin diseases. The main topics in which gender differences could be identified were choice of treatment, time to initiation of treatment, therapy response, adverse events, adherence and treatment satisfaction. For psoriasis, gender differences could be found in all aspects, while for the other skin diseases specific publications on gender differences are still missing. This systematic review shows numerous gender differences but also reveals major gaps in gender-specific care in dermatology which should be narrowed in the upcoming years to optimize a patient-centred, individualized, gender-equal healthcare. PROSPERO Registration: CRD42022306626.

Sex or gender differences in treatment outcomes of sepsis and septic shock.

Gender disparities in intensive care unit (ICU) treatment approaches and outcomes are evident. However, clinicians often pay little attention to the importance of biological sex and sociocultural gender in their treatment courses. Previous studies have reported that differences between sexes or genders can significantly affect the manifestation of diseases, diagnosis, clinicians' treatment decisions, scope of treatment, and treatment outcomes in the intensive care field. In addition, numerous reports have suggested that immunomodulatory effects of sex hormones and differences in gene expression from X chromosomes between genders might play a significant role in treatment outcomes of various diseases. However, results from clinical studies are conflicting. Recently, the need for customized treatment based on physical, physiological, and genetic differences between females and males and sociocultural characteristics of society have been increasingly emphasized. However, interest in and research into this field are remarkably lacking in Asian countries, including South Korea. Through this review, we hope to enhance our awareness of the importance of sex and gender in intensive care treatment and research by briefly summarizing several principal issues, mainly focusing on sex and sex hormone-based outcomes in patients admitted to the ICU with sepsis and septic shock.

Gender Differences in Treatment Outcomes for Eating Disorders: A Case-Matched, Retrospective Pre-Post Comparison.

Eating disorders (EDs) are increasingly emerging as a health risk in men, yet men remain underrepresented in ED research, including interventional trials. This underrepresentation of men may have facilitated the development of women-centered ED treatments that result in suboptimal outcomes for men. The present study retrospectively compared pre- vs. post-treatment outcomes between age-, diagnosis-, and length-of-treatment-matched samples of n = 200 men and n = 200 women with Anorexia Nervosa (AN), Bulimia Nervosa (BN), Binge Eating Disorder (BED), or Eating Disorder Not Otherwise Specified (EDNOS), treated in the same setting during the same period, and using the same measurements. Compared to women, men with AN showed marked improvements in weight gains during treatment as well as in ED-specific cognitions and general psychopathology. Likewise, men with BED showed marked weight loss during treatment compared to women with BED; ED-specific cognitions and general psychopathology outcomes were comparable in this case. For BN and EDNOS, weight, ED-specific cognitions, and general psychopathology outcomes remained largely comparable between men and women. Implications for treatments are discussed.

Остеопороз у чоловіків: стан проблеми, фактори ризику, діагностика, сучасні підходи до лікування

Остеопороз (ОП) у чоловіків — це гетерогенне захворювання, якому сьогодні приділяється мало уваги. Традиційно ОП вважався захворюванням, вражаючим лише жінок. Сформоване ставлення до чоловічого ОП як до рідкісної патології, тому відсутність настороженості призводить до того, що багато пацієнтів залишаються без лікування. Однак під час проведених досліджень установлено, що третина всіх переломів проксимального відділу стегна припадає на частку чоловічого населення, зумовлюючи високий рівень інвалідизації та первинної смертності. Проблема діагностики й лікування ОП останнім часом стає все актуальнішою у зв’язку зі старінням населення та виникненням ускладнень, властивих цій хворобі. Частота ОП-асоційованих переломів у чоловіків аналогічна частоті інфаркту міокарда і перевершує навіть частоту карциноми легенів і раку передміхурової залози. Результати для чоловіків-пацієнтів після перелому стегна виглядають гнітюче: одна третина (32 %) помирає протягом першого року, і тільки 21 % здатні самостійно жити в суспільстві через рік після перелому. Ця проблема найпоширеніша в осіб старше 70 років. Етіологія ОП у чоловіків може бути ідіопатичною або вторинною внаслідок гіпогонадизму, дефіциту вітаміну D і недостатнього вживання кальцію, гормонального лікування раку передміхурової залози, супутньої патології, використання лікарських препаратів, що впливають на метаболізм кісток. У даному огляді на основі сучасних європейських та американських рекомендацій розглянуті питання епідеміології ОП у чоловіків, основні принципи діагностики захворювання, засновані на даних оцінки клінічних проявів, анамнезу, включаючи цілеспрямований скринінг. Використання алгоритму FRAX дозволяє призначити лікування пацієнтам на етапі, коли показники мінеральної щільності кісткової тканини знаходяться в ме­жах остеопенічних значень і наявні додаткові фактори ризику. Детально описані методи інструментального та лабораторного обстеження пацієнтів. Підкреслені основні методи лікування, препаратами першого вибору для лікування ОП у чоловіків є бісфосфонати (алендронат, ризендронат, золедронова кислота) і терипаратид, другої лінії — деносумаб. Незважаючи на те, що доказова база цих препаратів саме в чоловіків є малою, сучасні дані не передбачають наявності гендерної різниці результатів лікування при аналогічних значеннях мінеральної щільності кісткової тканини. Своєчасна діагностика та профілактика ОП у чоловіків сприятимуть більш ранньому його виявленню, дозволять розпочати адекватну терапію та зменшити кількість переломів у таких пацієнтів.

Epidemiological and Clinical Gender Differences in OCD.

This review highlights recent research regarding gender differences in OCD, with a focus on prevalence, course of illness, symptom presentation, comorbidity, and treatment response. Overall, findings remain mixed. OCD may be more common among males in childhood, but is more common among females in adolescence and adulthood. Males tend to report an earlier age of onset and present with symptoms related to blasphemous thoughts. Females often describe symptom onset as occurring during or after puberty or pregnancy and present with symptoms related to contamination and/or aggressive obsessions. Females also tend to report significantly higher depression and anxiety. There are no reported gender differences in treatment outcome. Gender may play a role in the onset, presentation, and impact of OCD symptoms. However, more work is needed to account for differences across studies, with one promising future direction being the study of reproductive hormones.

PV-0533 HPV16 viral load may explain gender differences in treatment outcome of anal squamous cell carcinoma

PV-0533 HPV16 viral load may explain gender differences in treatment outcome of anal squamous cell carcinoma

Gender differences in tuberculosis treatment outcomes: a post hoc analysis of the REMoxTB study

BackgroundIn the REMoxTB study of 4-month treatment-shortening regimens containing moxifloxacin compared to the standard 6-month regimen for tuberculosis, the proportion of unfavourable outcomes for women was similar in all study arms, but men had more frequent unfavourable outcomes (bacteriologically or clinically defined failure or relapse within 18 months after randomisation) on the shortened moxifloxacin-containing regimens. The reason for this gender disparity in treatment outcome is poorly understood.MethodsThe gender differences in baseline variables were calculated, as was time to smear and culture conversion and Kaplan-Meier plots were constructed. In post hoc exploratory analyses, multivariable logistic regression modelling and an observed case analysis were used to explore factors associated with both gender and unfavourable treatment outcome.ResultsThe per-protocol population included 472/1548 (30%) women. Women were younger and had lower rates of cavitation, smoking and weight (all p < 0.05) and higher prevalence of HIV (10% vs 6%, p = 0.001). They received higher doses (mg/kg) than men of rifampicin, isoniazid, pyrazinamide and moxifloxacin (p ≤ 0.005). There was no difference in baseline smear grading or mycobacterial growth indicator tube (MGIT) time to positivity. Women converted to negative cultures more quickly than men on Lowenstein-Jensen (HR 1.14, p = 0.008) and MGIT media (HR 1.19, p < 0.001). In men, the presence of cavitation, positive HIV status, higher age, lower BMI and ‘ever smoked’ were independently associated with unfavourable treatment outcome. In women, only ‘ever smoked’ was independently associated with unfavourable treatment outcome. Only for cavitation was there a gender difference in treatment outcomes by regimen; their outcome in the 4-month arms was significantly poorer compared to the 6-month treatment arm (p < 0.001). Women, with or without cavities, and men without cavities had a similar outcome on all treatment arms (p = 0.218, 0.224 and 0.689 respectively). For all other covariate subgroups, there were no differences in treatment effects for men or women.ConclusionsGender differences in TB treatment responses for the shorter regimens in the REMoxTB study may be explained by poor outcomes in men with cavitation on the moxifloxacin-containing regimens. We observed that women with cavities, or without, on the 4-month moxifloxacin regimens had similar outcomes to all patients on the standard 6-month treatment. The biological reasons for this difference are poorly understood and require further exploration.

Treatment Outcomes for Women with Substance Use Disorders: a Critical Review of the Literature (2010–2016)

This review critically examines recent literature (2010–2016) on substance use outcomes in women-only treatment studies and gender differences in treatment outcomes in mixed-gender studies. We then focus on outcomes in three areas salient to women with substance use disorders (SUDs): treatment of comorbid post-traumatic stress disorder (PTSD), pregnancy and parenting interventions, and treatment for women in the criminal justice system. Favorable results were found for behavioral treatments for women including couples therapy and gender-responsive group therapy. When gender differences were observed in mixed-gender behavioral treatment, outcomes were more favorable in women than in men. However, when gender differences were observed in pharmacotherapy trial results, outcomes were worse for women. With regard to the three subgroups that we reviewed, most recent research on co-occurring PTSD and SUD has been secondary analysis studies which suggest that factors such as group attendance and co-occurring psychiatric disorders influence substance use outcomes. In contrast to the other two subgroups examined, behavioral treatments for pregnant women did not show superior outcomes when compared to control groups. However, buprenorphine was found to be safe and effective for use with pregnant women with an opioid use disorder. Finally, studies of treatment outcomes for women in the criminal justice system found preliminary evidence of efficacy for several behavioral treatments. Consistent with findings of previous reviews, gender alone did not necessarily predict treatment response; rather, interaction of gender and other factors affected outcomes. Evidence showing worse outcomes for women in pharmacotherapy trials, with the exception of buprenorphine with pregnant women, further reinforces the need for research to evaluate differential treatment outcomes for men and women.

Men\u2019s and women\u2019s response to treatment and perceptions of outcomes in a randomized controlled trial of injectable opioid assisted treatment for severe opioid use disorder

BackgroundTo test whether there are gender differences in treatment outcomes among patients receiving injectable opioids for the treatment of long-term opioid-dependence. The study additionally explores whether men and women have different perceptions of treatment effectiveness.MethodsThis study is a secondary analysis from SALOME, a double-blind, phase III, randomized controlled trial testing the non-inferiorirty of injectable hydromorphone to injectable diacetylmorphine among 202 long-term street opioid injectors in Vancouver (Canada). Given this was a secondary analysis, no a priori power calaculation was conducted. Differences in baseline characteristics and six-month treatment outcomes (illicit heroin use, opioid use, crack cocaine use, non-legal activities, physical and psychological health scores, urine positive for street heroin markers, and retention) were analysed by gender using fitted models. Responses to an open ended question on reasons for treatment effectiveness were explored with a thematic analysis.ResultsMen and women differed significantly on a number of characteristics at baseline. For example, women were significantly younger, presented to treatment with significantly higher rates of prior month sex work (31.5% vs. 0%), and used significantly more crack cocaine (14.71 vs. 8.38 days). After six-months of treatment there were no significant differences in treatment outcomes by gender, after adjusting for baseline values. For both men and women, improved health and quality of life were the most common reasons provided for treatment effectiveness, however women were more specific in the types of health improvements.ConclusionsDespite presenting to treatment with vulnerabilities not faced to the same extent by men, at six-months women did not differ significantly from men in tested trial efficacy outcomes. While the primary outcome in the trial was the reduction of illicit opioid use, in the open-ended responses both men and women focused their comments on improvement in health and quality of life as reasons for treatment effectiveness. The supervised model of care with injectable medications provides a particularly suitable framework for providing care to opioid-dependent men and women not attracted or retained by other treatments. The absence of statistical differences reported in this secondary analysis may be due to lack of adequate statistical power to detect meaningful effects.Trial registrationThis trial is registered with ClinicalTrials.gov (NCT01447212) Registered: October 4, 2011 at the following link: https://clinicaltrials.gov/ct2/show/NCT01447212.

Gender Differences in Adverse Drug Reactions during HAART Therapy in HIV/AIDS Patients at a Tertiary Care Hospital Penang, Malaysia

Aims and objective: Current study is aimed to explore and observe adverse drug reactions occurrence of antiretroviral therapy and to examine the gender differences in treatment outcomes of HIV/AIDS patients during HAART therapy. Method: An observational retrospective study of all patients on HAART therapy diagnosed with HIV infection from January 2007 to December 2012 was conducted at infectious disease department of Hospital Pulau Pinang, Malaysia. Patients socio-demographic, clinical and laboratory data was retrieved via self developed validated data collection form. Results: Out of 743 patients 571 (76.8%) were male and 172 (23.1%) were female patients. A total number of 425 (57.2%) adverse drug reactions were reported among which 311 (73.1%) occurred in males and 114 (26.8%) in female patients, with a significant statistical relationship (p=0.02, OR=1.21). Out of total ADRs (57.2%) observed in both genders, a significant association was observed in Lipodystrophy (p=0.05), anemia (p=0.02), Peripheral Neuropathy (p=0.02) and pancreatitis (p=0.01). A total of 455 (79.6%) male and 139 (80.8%) female patients have improvement in CD4 cells count at the final follow up, a significant association (p=0.05) was observed among the mode of transmission and treatment outcome. Conclusion: Overall, the ADRs observed in both gender emphasize the importance of developing safer HAART regimens and managing these adverse effects in a timely manner in order to avoid long-term health consequences.

Gender differences in treatment outcomes among 15-49 year olds with smear-positive pulmonary tuberculosis in Kenya.

To determine gender differences in treatment outcomes among 15-49 year olds with smear-positive pulmonary tuberculosis (PTB) and factors associated with poor outcomes in Kenya. Retrospective descriptive cohort. Of 16 056 subjects analysed, 38% were female and 62% male. Females had a higher risk of poor treatment outcome than males (12% vs. 10%, P < 0.001; adjusted OR 1.29, 95%CI 1.16-1.44, P < 0.001). In the first multivariate model, restricting the analysis to human immunodeficiency virus (HIV) positive patients and adjusting for risk factors and clustering, females had a non-significantly lower risk of poor outcome (OR 0.99, 95%CI 0.86-1.13, P = 0.844). In the model restricted to HIV-negative patients, a non-significantly lower risk was found (OR 0.89, 95%CI 0.73-1.09, P = 0.267). In the second model, restricting analysis to patients on antiretroviral therapy (ART) and adjusting for risk factors and clustering, females had a non-significantly lower risk of poor PTB treatment outcomes (OR 0.98, 95%CI 0.84-1.14, P = 0.792). In the model restricted to HIV-positive patients not on ART, a non-significantly higher risk was found (OR 1.15, 95%CI 0.79-1.67, P = 0.461). Females of reproductive age are likely to have poorer treatment outcomes than males. Among females, not commencing ART during anti-tuberculosis treatment seemed to be associated with poor outcomes.

A randomized controlled trial of prison-initiated buprenorphine: Prison outcomes and community treatment entry

BackgroundBuprenorphine is a promising treatment for heroin addiction. However, little is known regarding its provision to pre-release prisoners with heroin dependence histories who were not opioid-tolerant, the relative effectiveness of the post-release setting in which it is provided, and gender differences in treatment outcome in this population. MethodsThis is the first randomized clinical trial of prison-initiated buprenorphine provided to male and female inmates in the US who were previously heroin-dependent prior to incarceration. A total of 211 participants with 3–9 months remaining in prison were randomized to one of four conditions formed by crossing In-Prison Treatment Condition (received buprenorphine vs. counseling only) and Post-release Service Setting (at an opioid treatment center vs. a community health center). Outcome measures were: entered prison treatment; completed prison treatment; and entered community treatment 10 days post-release. ResultsThere was a significant main effect (p=.006) for entering prison treatment favoring the In-Prison buprenorphine Treatment Condition (99.0% vs. 80.4%). Regarding completing prison treatment, the only significant effect was Gender, with women significantly (p<.001) more likely to complete than men (85.7% vs. 52.7%). There was a significant main effect (p=.012) for community treatment entry, favoring the In-Prison buprenorphine Treatment Condition (47.5% vs. 33.7%). ConclusionsBuprenorphine appears feasible and acceptable to prisoners who were not opioid-tolerant and can facilitate community treatment entry. However, concerns remain with in-prison treatment termination due to attempted diversion of medication.

English

English

A gender analysis of the study of pharmacotherapy of psychotic depression (STOP-PD): gender and age as predictors of response and treatment-associated changes in body mass index and metabolic measures.

Gender differences exist in psychiatric disorders; however, gender has not been well studied in psychotic depression. This analysis of the largest clinical trial in psychotic depression examined the effects of age and gender on clinical characteristics and predictors of treatment outcome and treatment-associated changes in body mass index (BMI) and metabolic measures. Secondary analyses were performed on data from 259 subjects with major depressive disorder with psychotic features (DSM-IV-TR) aged 18-93 years in the double-blind randomized controlled trial of olanzapine plus sertraline versus olanzapine plus placebo for psychotic depression (Study of Pharmacotherapy of Psychotic Depression). Sociodemographic factors, clinical characteristics, treatment outcome, and treatment-associated changes in BMI and metabolic measures were analyzed by gender and age. Subjects were enrolled from December 2002 to June 2007. Female gender was associated with divorced (χ(2)(1) = 5.3, P = .03) or widowed (χ(2)(1) = 8.1, P ≤ .01) marital status. Comorbid anxiety disorders were more common in women than in men (χ(2)(1) = 4.9, P = .03). Hallucinations (χ(2)(1) = 7.8, P = .005) and delusions with disorganization (t(257) = -2.10, P = .04) were significantly associated with female gender, as were higher cholesterol measures (χ(2)(1) = 7.15, P = .008). There were no significant interactions between treatment and gender in terms of change in BMI. Gender was not associated with treatment response. This study is the first analysis of gender and age as predictors of treatment outcome and treatment-associated changes in BMI and metabolic adverse effects in psychotic depression. Gender differences exist in patients with psychotic depression, most notably with regard to the presence of hallucinations. Female gender was associated with metabolic measures. Future studies with larger sample sizes may detect small gender differences in treatment outcome and treatment-associated changes in BMI and metabolic measures in psychotic depression. ClinicalTrials.gov identifier: NCT00056472.

Gender differences in HIV disease progression and treatment outcomes among HIV patients one year after starting antiretroviral treatment (ART) in Dar es Salaam, Tanzania

BackgroundWe investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors.MethodsWe conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models.ResultsOf 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02).ConclusionWe observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences.

Gender differences in treatment outcomes of tuberculosis patients in Taiwan: a prospective observational study

Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50~60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12–3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.

Gender Is A Major Determinant of Cytidine Analogue Metabolism and May Contribute to Differences in Treatment Outcomes

Abstract 1434Cytidine analogues are mainstays in hematologic malignancy therapy. One documented limitation of therapy is interindividual variability in cytidine analogue pharmacokinetics that compromises predictability, safety and efficacy. Causes of interindividual variability include single nucleotide polymorphisms (SNPs) in cytidine metabolizing enzymes, particularly cytidine deaminase (CDA): the CDA SNP A79C (rs2072671) is present in >70% of Caucasians and decreases CDA enzyme activity. Gender is another known genetic determinant of cytidine analogue clinical activity, although the pathway is unknown (Dimopoulou et al, Ann Oncol 2004). With high dose cytarabine therapy, CDA may be saturated, dampening the clinical impact of CDA SNPs. However, the recently approved cytidine analogues 5-azacytidine and decitabine are used as single agents at relatively low doses, and interindividual variability could have greater clinical significance, since drug levels may be close to minimum thresholds required for efficacy. To evaluate this possibility, the impact of A79C and gender on treatment outcomes was examined in a cohort of patients with myelodysplastic syndrome (MDS, n=127) and acute myeloid leukemia (AML, n=74) classified by WHO criteria, initiated on treatment between 1/2002 and 12/2007, with IRB approved tissue-banked bone marrow samples available for analysis for the A79C SNP by sequencing and SNP array, and with verifiable follow-up and survival annotation. Other variables analyzed were those known to have major prognostic importance in patients with MDS and AML (bone marrow myeloblast percentage, karyotype, age). Patients were analyzed in three treatment groups: (i) did not receive cytidine analogues (n=35), (ii) treated with cytarabine (n=76), (iii) treated with 5-azacytidine or decitabine (n=90). In all three treatment groups, heterozygosity or homozygosity for A79C was not associated with significant differences in overall survival (OS). Similarly, there was no significant difference in overall survival in females versus males who were treated with cytarabine or who did not receive cytidine analogues. However, in the 5-azacytidine/decitabine treatment group, females had significantly longer overall survival than males (median 1033 v 563 days, Log Rank p=0.014). In multivariate analysis incorporating age, karyotype, bone marrow blast percentage and A79C, only age, gender and karyotype were significantly (Cox Proportional Hazards p<0.01) associated with survival, with the hazard ratio for female gender 0.356 (95%CI 0.165–0.766). An important caveat is that MDS in females has a less aggressive natural history (Nosslinger et al, Ann Oncol 2010), therefore, it is possible that gender differences in cytidine analogue metabolism do not underlie the difference in overall survival. Nonetheless, in AML myeloblasts (GSE15434) and normal liver tissue (measured by microarray), CDA mRNA expression in females was significantly lower than in males (Wilcoxon test p=0.005 and p=0.025 respectively). To measure functional CDA activity, uridine conversion from cytidine by plasma was measured by uHPLC (Dionex). As expected, there was a significant 2-fold decrease in mean enzyme activity in individuals homozygous for the A79C variant (CC, n=32) compared to individuals homozygous for the ancestral allele (AA, n=32, t-test p=0.02). However, the decrease in mean enzyme activity in females (n=48) compared to males (n=48) was even greater (3-fold, t-test p<0.001). In an analysis of decitabine pharmacokinetics after administration of oral decitabine 1 mg/kg to female (n=18) and male (n=18) adult mice, plasma levels of decitabine measured by LCMSMS were consistently higher in females at all time-points (1.169-4.375 fold at the different time points, paired t-test p=0.001). In conclusion, decreased cytidine analogue conversion to uridine counterparts in females, most likely from differences in CDA expression, could be relevant to gender differences in treatment outcomes with 5-azacytidine or decitabine. Disclosures:No relevant conflicts of interest to declare.

Combining Qualitative and Quantitative Evidence to Determine Factors Leading to Late Presentation for Antiretroviral Therapy in Malawi

BackgroundTreatment seeking delays among people living with HIV have adverse consequences for outcome. Gender differences in treatment outcomes have been observed in sub-Saharan Africa.ObjectiveTo better understand antiretroviral treatment (ART) seeking behaviour in HIV-infected adults in rural Malawi.MethodsQualitative interviews with male and female participants in an ART cohort study at a treatment site in rural northern Malawi triangulated with analysis of baseline clinical and demographic data for 365 individuals attending sequentially for ART screening between January 2008 and September 2009.Results43% of the cohort presented with late stage HIV disease classified as WHO stage 3/4. Respondents reported that women's frequency of testing, health awareness and commitment to children led to earlier ART uptake and that men's commitment to wider social networks of influence, masculine ideals of strength, and success with sexual and marital partners led them to refuse treatment until they were sick. Quantitative analysis of the screening cohort provided supporting evidence for these expressed views. Overall, male gender (adjusted OR 2.3, 95% CI1.3–3.9) and never being married (adjusted OR 4.1, 95% CI1.5–11.5) were risk factors for late presentation, whereas having ≥3 dependent children was associated with earlier presentation (adjusted OR 0.31, 95% CI0.15–0.63),compared to those with no dependent children.ConclusionGender-specific barriers and facilitators operate throughout the whole process of seeking care. Further efforts to enrol men into care earlier should focus on the masculine characteristics that they value, and the risks to these of severe health decline. Our results emphasise the value of exploring as well as identifying behavioural correlates of late presentation.

Gender Differences in Treatment Outcomes Among Participants in a Mixed-Gender Substance Abuse Aftercare Program

This study examined gender and gender-related predictors in multiple outcomes of substance abuse aftercare treatment among 78 females and 141 males enrolled in a mixed-gender aftercare program in Massachusetts from 1994 to 1996. Female participants entered the program with higher needs than their male counterparts, showing a worse condition in almost all baseline characteristics, of which many are statistically significant. The generalized estimating equations (GEE) model revealed significant gender differences in the two treatment outcomes of employment income and illegal activity days. Also, many significant gender-related predictors and interaction variables were found.

Gender Differences in Outcome at 2-Year Follow-Up of Treated Bipolar and Depressed Alcoholics

Alcohol dependence and affective disorders are significant health problems, and their co-occurrence is mutually detrimental. There are few long-term studies on the impact of treatment on the prognosis of these comorbid disorders. We wished to study if the impact of effective inpatient integrated treatment for these co-occurring disorders was maintained 2 years after discharge from the hospital. A total of 189 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol dependence and either bipolar disorder or depression were recruited, assessed, and assigned to an inpatient treatment unit. Following intensive integrated treatment that was designed to integrate psychotherapy with pharmacotherapy, affective disorder with substance use disorder treatment, and inpatient with outpatient therapy, this population was followed for 2 years after discharge. Treatment improvements above baseline that were achieved over the course of the 4-week intensive inpatient treatment were essentially maintained over a 2-year outpatient period. Depression, elation, anxiety, and craving scores all fell, as did all drinking outcome measures in both depressed and bipolar alcohol-dependent groups. Findings suggested that women with a diagnosis of bipolar disorder reported higher levels of depression and anxiety symptoms than male bipolar patients at 2-year follow-up. More women than men remained abstinent at 2 years after treatment, with this difference mainly in the depressed sample. Comorbid bipolar alcoholics and depressed alcoholics can be treated successfully together on an integrated inpatient treatment program, and the benefits can last for up to 2 years. There also appeared to be significant gender differences in treatment outcomes.