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Note that it remains controversial whether LMWH reduction in major VTE if a pharmacologic prophylaxis strategy is should be weight adjusted or doubled after 20 weeks buy generic extra super levitra 100 mg online, when to be expected to achieve a mortality benefit order extra super levitra 100 mg on line. Taking the CFRs into increases in plasma volume and glomerular filtration rate may lead account buy 100mg extra super levitra with mastercard, patients would require a postpartum VTE risk of 1% for to a reduced anti-Xa effect. Whether these lower anti-Xa levels LMWH prophylaxis to likely provide a net clinical benefit in the lead to a reduced efficacy is unknown. Similarly, in the antepartum period, 388 American Society of Hematology Table 2. Pooled proportion of major VTE in antepartum and postpartum periods in patients with prior VTE (provoked or unprovoked or estrogen associated) on prophylactic anticoagulants versus control Antepartum anticoagulants No antepartum anticoagulants Postpartum anticoagulants No postpartum anticoagulants RCTs Rodgeretal24 1/21 0/15 2/36 - Gatesetal54 0/8 0/8 1/11 - Howelletal56 0/20 1/20 0/40 - Cohort studies Brill-Edwardsetal34(prospective)* - 3/125 3/125 - Pabingeretal12(retrospective)† 0/87 8/197 5/97 10/187 Bauersachsetal22(prospective)* 0/339 - 1/383 - Tengbornetal57(retrospective)† 3/20 5/67 2/57 2/30 DeStefanoetal58(retrospective)† - 9/155 - 10/120 Laoetal59(retrospective)† - 1/26 0/24 - Lindqvistetal60(prospective)* 2/326 - 2/326 - Roetersetal48(retrospective)* 2/53 0/32 5/85 - Total 8/874;0. Taking into consideration all of the other downsides as homozygous factor V Leiden (FVL)30,31 or homozygous prothrom- of prolonged antenatal LMWH use, most clinicians and patients bin gene variant (PGV),31 antithrombin deficiency,32 and those who would not likely consider antenatal LMWH if the antenatal risk of are double heterozygotes for thrombophilia. Each scenario requires an individual patient that published data on VTE risk in otherwise asymptomatic discussion, taking into account patient preferences and values, to pregnant women with antithrombin deficiency are limited to small come to a common decision on prophylaxis. For example, some case series, but most of the literature supports a high enough risk to patients with needle phobia may be more comfortable with a higher warrant thromboprophylaxis. As outlined above, most clinicians/patients would seek an absolute be extended to all women with prior provoked VTE that are not risk of antenatal VTE that exceeds 1% before even considering estrogen associated (Table 3) regardless of thrombophilia, but antepartum LMWH prophylaxis. In Tables 2 and 3, I have uncertainty remains because the high upper bound of the 95% summarized the studies exploring the risk of pregnancy-associated confidence interval around the pooled estimate is higher than 3% VTE in women with prior VTE and provide pooled proportions of (Table 3). The risk factors VTE and should not receive anticoagulant prophylaxis. Large for antepartum VTE that appear to increase the risk of antenatal prospective cohort studies of patients with FVL and PGV35-38 and VTE 10-fold or are associated with 1% absolute risk of VTE RCTs (Table 4) demonstrate a low antenatal VTE risk with these include: prior VTE if unprovoked or if associated with a prior common thrombophilias without antenatal prophylaxis. Pooled proportion of major VTE in antepartum periods without anticoagulant prophylaxis in patient subgroups with prior unprovoked VTE, prior provoked VTE, and prior estrogen-associated VTE No antepartum LMWH and No antepartum LMWH and prior provoked No antepartum LMWH and prior Cohort study prior unprovoked VTE VTE (not estrogen associated) estrogen-associated VTE Brill-Edwards et al34 (prospective)* 2/43 0/33 1/51 Pabinger et al12 (retrospective)† 0/15 1/16 7/93 De Stefano et al58 (retrospective)† 2/47 0/36 7/72 Roeters et al48 (retrospective)† 0/6 0/9 0/17 Total 4/111; 3. Pooled proportion of major VTE in antepartum and postpartum periods in thrombophilic patients without prior VTE on prophylactic LMWH versus control with or without ASA in pregnancy RCT Antepartum LMWH No antepartum LMWH Postpartum LMWH Rodger et al24 0/125 0/128 0/253 de Vries et al49 0/70 0/69 1/139 Gris et al, 201150 0/14 0/18 0/32 Gris et al, 201051 0/13 0/13 0/27 Martinelli et al52 0/7 0/8 - Kaandorp et al25 0/13 0/34 - Total 0/242; 0% (95% CI 0%–1. Postpartum period is associated with higher risk and tum infection, postpartum hemorrhage, smoking, BMI 25 kg/m2, has distinct risk factors for VTE intrauterine growth restriction, preeclampsia, stillbirth, varicose Compared with age-matched, nonpregnant controls, the daily risk of veins, inflammatory bowel disease, preterm birth, and age 35 years. Therefore, given an absolute risk of postpartum VTE of 0. The risk factors for postpartum need for research to explore alternative strategies that, again, will VTE that increase risk 20-fold or are associated with a 1% need to be balanced against a higher bleeding risk. Indeed, the absolute risk of VTE are: immobilization (strict bed rest for a week Highlow RCT (www. Consensus guidelines also 60-fold or are associated with an absolute risk of VTE 3% are suggest adding mechanical methods to pharmacoprophylaxis in 44 high-risk patients in the postpartum period18 and certainly patients antithrombin deficiency, combined thrombophilias, and prior VTE (all prior VTEs regardless of whether unprovoked, provoked, or with prior VTE would warrant this added measure. Finally, although not well explored, perhaps other combinations of independent risk factors would Patient counseling exceed these thresholds. These other risk factors might include In addition to the individualized discussion regarding anticoagulant family history of VTE,45 prior superficial phlebitis,46 weaker prophylaxis suggested, all women at high risk of pregnancy- thrombophilias (heterozygous FVL or heterozygous PGV or protein associated VTE should also be counseled about the signs and C deficiency or protein S deficiency), emergency C-section, postpar- symptoms of DVT and PE and an action plan developed should Table 5. Recommendations for thromboprophylaxis in pregnancy Patient subgroup Antepartum prophylaxis Postpartum Prophylaxis Unselected pregnant women No No Weak thrombophilia with no personal history of VTE No Probably not (see text) Prior provoked VTE (surgery, trauma, immobilization) No Yes without estrogen trigger or thrombophilia Prior unprovoked VTE or estrogen associated VTE Yes Yes* Combinations of “other risk factors”† No Possibly† Antepartum immobilization (strict bed rest for 1 wk) Yes (duringimmobility) Yes and BMI 25 kg/m2 Potent thrombophilia Yes Yes WeakthrombophiliaindicatesheterozygousFVLorPGV;potentthrombophilia,antithrombindeficiency,homozygousFVL,homozygousPGV,orcombineddeficiencies. Deep vein thrombosis during pregnancy and the VTE-mimicking symptoms are common in pregnancy. They should puerperium: a meta-analysis of the period of risk and the leg of not be alarmed by the gradual development of bilateral leg edema or presentation. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Women with a prior VTE who remain on vitamin K antagonists Haemost. Calibrated automated should be counseled to discontinue them as soon as they become thrombin generation in normal uncomplicated pregnancy. Thromb pregnant (missed menses and/or positive urine pregnancy test). Kjellberg U, Andersson NE, Rosen S, Tengborn L, Hellgren M. APC inhibitors, reliable contraceptive methods are advised until a resistance and other haemostatic variables during pregnancy and planned pregnancy. Before a planned pregnancy, these drugs should puerperium. D-dimer levels during delivery In women who become pregnant and have had a recent VTE, the and the postpartum. Prophylaxis for venous thromboem- by the age of the recent VTE. In the absence of pregnancy-specific bolic disease in pregnancy and the early postnatal period. Cochrane research to guide us, my approach is to start full-dose therapeutic Database Syst Rev. LMWH immediately if the VTE occurred in the last month (eg, 12. Risk of pregnancy- enoxaparin 1 mg/kg q 12 h or dalteparin 200 units/kg q 24 h, or associated recurrent venous thromboembolism in women with a history tinzaparin 175 units/kg q 24 h). I offer aggressive prophylaxis in the of venous thrombosis. Thigh-length versus below-knee stockings initiated in the next 24 hours if the VTE occurred in the last 12 for deep venous thrombosis prophylaxis after stroke: a randomized trial. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein 5000 units, or tinzaparin 4500 all given sc daily). In summary, as our knowledge of the absolute risks of pharmacopro- 15. Effectiveness of intermittent phylaxis in pregnancy and VTE risk stratification in pregnancy has pneumatic compression in reduction of risk of deep vein thrombosis in evolved, we have developed a clearer picture of who should and patients who have had a stroke (CLOTS 3): a multicentre randomised who should not receive pharmacoprophylaxis to prevent pregnancy- controlled trial. Pradax Product Monograph: Dabiga- this knowledge to strike the right balance in preventing pregnancy- tran Etixilate Capsules; 2009. Xarelto Product Monograph, Rivaroxaban Tablet; 2008. VTE, thrombophilia, Disclosures antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Conflict-of-interest disclosure: The author declares no competing Prevention of Thrombosis, 9th ed: American College of Chest Physi- financial interests. Off-label drug use: LMWH to prevent VTE in cians Evidence-Based Clinical Practice Guidelines. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophy- Correspondence laxis: a meta-analysis. Marc Rodger, Chief, Division of Hematology, Senior Scientist, 20. Osteoporotic fractures and the recurrence of thromboem- Ottawa Hospital Research Institute, Ottawa Hospital, General bolism during pregnancy and the puerperium in 184 women undergoing Campus, 1812-E Box 201, 501 Smyth Road, Ottawa, ON, Canada thromboprophylaxis with heparin. Long-term dalteparin in pregnancy not associated with a decrease in bone mineral density: References substudy of a randomized controlled trial. Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Risk stratification and additional risk factors from a London perinatal database. Venous thromboembolism mortality in the United States, 1998 to 2005. Antepartum dalteparin Reviewing maternal deaths to make motherhood safer: 2006-2008: the versus no antepartum dalteparin for the prevention of pregnancy Eighth Report of the Confidential Enquiries into Maternal Deaths in the complications in pregnant women with thrombophilia (TIPPS): a United Kingdom. Aspirin plus heparin or versus no antepartum dalteparin for the prevention of pregnancy aspirin alone in women with recurrent miscarriage. An ultrasound study of gesta- Intervention Study: a multicentre randomised controlled trial of low tional and postural changes in the deep venous system of the leg in molecular weight heparin and low dose aspirin in women with recurrent pregnancy. Huhle G, Geberth M, Hoffmann U, Heene DL, Harenberg J. The value of family history as a risk indicator for venous ment of heparin-associated thrombocytopenia in pregnancy with subcu- thrombosis. Comparing deep vein thrombosis and pulmonary embolism during pregnancy or multiple competing interventions in the absence of randomized trials post partum: a population-based, case-control study. Risk factors for first venous factors of venous thrombosis: a hospital-based case-control study.

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A lamivudine (3TC)-based backbone in conjunction with a boosted protease inhibitor (PI) is sufficient to achieve virologic suppression in the presence of M184V mutations extra super levitra 100 mg on-line. Randomized proven extra super levitra 100 mg, controlled buy extra super levitra 100 mg lowest price, 48 week study of switching stavudine and/or pro- tease inhibitors to Combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients. Ritonavir boosted indinavir treatment as a simplified maintenance “mono”- therapy for HIV infection. Maraviroc plus raltegravir failed to maintain virological suppression in HIV-infected patients with lipohypertrophy: results from the ROCnRAL ANRS 157 study. TRIZAL study: switching from successful HAART to Trizivir (abacavir lamivu- dine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results. Switch to efavirenz (EFV) after protease-inhibitor (PI)-failure: explorative analysis of outcome by baseline viral VS tolerability failure. Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy. Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy. Resistant minority species are rarely observed in patients on darunavir/ritonavir monotherapy. Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study. The safety and efficacy of switching stavudine to tenofovir df in com- bination with lamivudine and efavirenz in hiv-1-infected patients: three-year follow-up after switching therapy. Efficacy and safety of switching from boosted lopinavir to boosted atazanavir in patients with virological suppression receiving a LPV/r-containing HAART: the ATAZIP study. J AIDS 2009, 51:29-36 Marcelin AG, Lambert-Niclot S, Peytavin G, et al. Baseline HIV RNA ultrasensitive assay and viral DNA predict rise in plasma viral load in patients of MONOI-ANRS 136 Trial. Induction with abacavir/lamivudine/zidovudine plus efavirenz for 48 weeks followed by 48-week maintenance with abacavir/lamivudine/zidovudine alone in antiretroviral-naive HIV- 1-infected patients. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir- lamivudine: a randomized, 96-week trial. Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy. HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI) or LPV/r + raltegravir as second-line anti- retroviral therapy. Reversibility of lipoatrophy in HIV-infected patients 2 years after switching from a thymidine analogue to abacavir: the MITOX Extension Study. Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with HIV infection. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. Effectiveness of protease inhibitor monotherapy versus combination anti- retroviral maintenance therapy: a meta-analysis. PLoS One 2011, 6:e22003 McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons ran- domized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202. Effect of reducing the dose of stavudine on body composition, bone density, and markers of mitochondrial toxicity in HIV-infected subjects: a randomized, controlled study. Mitochondrial function, inflammation, fat and bone in HIV lipoat- rophy: randomized study of uridine supplementation or switch to tenofovir. Improvements in lipoatrophy, mitochondrial DNA levels and fat apoptosis after replacing stavudine with abacavir or zidovudine. Improvement in lipoatrophy associated with HAART in HIV- infected patients switched from stavudine to abacavir or zidovudine: the results of the TARHEEL study. Lopinavir/ritonavir monotherapy versus current treatment contin- uation for maintenance therapy of HIV-1 infection: the KALESOLO trial. How to switch ART 221 Milinkovic A, Martinez E, Lopez S, et al. The impact of reducing stavudine dose versus switching to tenofovir on plasma lipids, body composition and mitochondrial function in HIV-infected patients. Reasons for stopping antiretrovirals used in an initial highly active anti- retroviral regimen: increased incidence of stopping due to toxicity or patient/physician choice in patients with hepatitis C coinfection. Simplification therapy with once-daily emtricitabine, didanosine, and efavirenz in HIV-1-infected adults with viral suppression receiving a PI-based regimen: a randomized trial. Dual therapy with etravirine plus raltegravir for virologically suppressed HIV- infected patients: a pilot study. J Antimicrob Chemother 2014, 69:742-8 Moyle G, Baldwin C, Langroudi B, Mandalia S, Gazzard BG. A 48 week, randomized, open label comparison of three abacavir-based substitution approaches in the management of dyslipidemia and peripheral lipoatrophy. A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. Early vs deferred HAART switch in heavily pre-treated HIV patients with low viral load level and stable CD4 cell count. Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine or to efavirenz in patients with HIV infection and long-lasting viral suppression. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial. Viral rebound after switch to maraviroc/raltegravir dual therapy in highly experienced and virologically suppressed patients with HIV-1 infection. Four-year outcome of a PI and NRTI-sparing salvage regimen: maraviroc, ral- tegravir, etravirine. Monotherapy with Lopinavir/Ritonavir as maintenance after HIV-1 viral suppression: results of a 96-week randomized, controlled, open-label, pilot trial (KalMo study). A Switch in Therapy to a Reverse Transcriptase Inhibitor Sparing Combination of Lopinavir/Ritonavir and Raltegravir in Virologically Suppressed HIV-infected Patients: A Pilot Randomized Trial to Assess Efficacy and Safety Profile: The KITE Study. AIDS Res Hum Retroviruses 2012, 28:1196- 2062012 Feb 26. A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in HIV infection. Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. Saquinavir/ritonavir monotherapy as a new nucleoside-sparing main- tenance strategy in long-term virologically suppressed HIV-infected patients. High virological failure rate in HIV patients after switching to a regimen with two nucleoside reverse transcriptase inhibitors plus tenofovir. Switching to dual therapy (atazanavir/ritonavir+ lamivudine) vs. No evidence for evolution of genotypic resistance after three years of treatment with darunavir/ritonavir, with or without nucleoside analogues. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucle- osides for maintenance therapy of HIV. AIDS 2008;22: Pulido F, Delgado R, Pérez-Valero I, et al. Long-term (4 years) efficacy of lopinavir/ritonavir monotherapy for maintenance of HIV suppression. Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtric- itabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ ANRS143 ran- domised non-inferiority trial. Lancet 2014, Aug 5, pub ahead of print Rasmussen TA, Jensen D, Tolstrup M, et al. Comparison of bone and renal effects in HIV-infected adults switch- ing to abacavir or tenofovir based therapy in a randomized trial. Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: ADAM study.

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If This looks at the distribution of the cases/patients best extra super levitra 100mg. Is it children 100mg extra super levitra for sale, incidence is 20/2500×1000 or 8 cases per every old people order extra super levitra 100mg with mastercard, prisoners, students, farmers, female, etc? Is it during teen some circumstances it is expressed in different ways age, rain or dry season, etc? How examples include morbidity rates, mortality rates, much, i. Knowing all these factors Difference between incidence and prevalence will help to plan cost-effectively on how to manage the disease in question. Assume the incidence is the amount of water being brought to a dam over a specific period of time Determinants (e. If there is no leakage factors to the occurrence of disease, or why an indi- in the dam, the amount of water in the dam vidual gets that ‘disease’. For example what are the 428 Epidemiology in Gynecological Diseases determinants of infertility, meaning why does 2. Primary prevention can be defined as the action someone get infertility? This means what are factors taken prior to the onset of disease, which re- that contribute for someone to become infertile moves the possibility that the disease will ever [prevalence of sexually transmitted disease (STI), occur. It is done in those people who have risk lack of condom use, poverty, number of partners]. It is done through health promotion What influences the occurrence of the infertility? Is (health education, environmental control, a contact with the causative agent enough for the nutritional interventions, lifestyle/behavior infertility to occur or is there something else (influ- changes etc. For example primary Careful analysis of determinants helps to find and prevention of cervical cancer may include the strengthen the evidence of the link between the use of human papillomavirus vaccine. Secondary prevention is defined as efforts that aim tive control measures. Specified population This includes specific interventions like early diagnosis (e. For example hyperemesis to arrest the disease progress by diagnosing it occurs commonly in primigravid women. For ‘primigravid women’ is the specified population for example, visual inspection with acetic acid hyperemesis gravidarum. The same applies to the (VIA), visual inspection with Lugol’s iodine population that gets cervical cancer, or ectopic (VIL) and Papanicolaou (Pap) smear aim to pregnancy etc. If the affected population is known, discover cancer of the cervix before it is management efforts will be focused on that small obvious and cryotherapy is used to remove group. The success rate will be higher compared precancerous cells in the cervix and this will be with dealing with the whole population randomly. Tertiary prevention consists of measures aimed at Prevention is defined as actions aimed at eradicat- limiting the impact of long-term disease and ing, eliminating or minimizing the occurrence of disability by eliminating or reducing impair- disease, or retarding the progress of the disease and ment, disability and handicap that may be its impact. It aims to minimize suffering and levels of prevention – primordial, primary, second- maximize the quality of life in the remaining ary and tertiary. For example tertiary prevention of cervical cancer 1. Primordial prevention is the combination of actions involves the diagnosis and treatment of con- and measures that reduce or eliminate the emer- firmed cases of cancer. Treatment is through gence of risk factors in the population. Here surgery, radiotherapy and sometimes chemo- efforts are directed toward discouraging those therapy. For example early Some authors talk about quaternary prevention. This sexual debut and multiple sexual partners are risk consists of actions that identify patients at risk of factors for the development of cancer of the cer- over-diagnosis or over-medication and that protect vix or STI. At primordial level of prevention, them from excessive medical intervention which children will be sensitized to delay their sexual may result in iatrogenesis, (inadvertent adverse debut and to avoid multiple sexual partners. For example over-diagnosis of obstruc- through individual and mass education. This may increase the Disease burden is the effect/impact of a disease in a rate of ruptured uterus in subsequent pregnancies if community measured by financial cost, mortality, emergency services are not very good. It is often quantified the proper management of labor may be considered in terms of quality-adjusted life years (QALYs), as quaternary prevention disability-adjusted life years (DALYs) or years lost Successful prevention depends on knowledge of due to disability (YLD) which combines the bur- causation, dynamics of transmission, identification den due to both death and morbidity into one in- of risk factors and risk groups, availability of dex. This allows for the comparison of the disease prophylactic or early detection and treatment burden for varying risk factors or diseases. It also measures, an organization for applying these meas- makes it possible to predict the possible impact of ures to appropriate persons or groups, and continu- health interventions in a community. Without these, the likelihood of success- the fraction of actual disease burden in the com- fully preventing any disease in the community is munity. It is like the tip of an iceberg: what is seen very low. The difference between what is seen in the health facility and what is actually Outcome of preventive measures present in the community depends on the health- These are usually categorized into control, elimina- seeking behavior of the respective community. If tion, eradication and extinction depending on the most of the sick people in the community seek achievement: medical treatment in health facilities (good health- seeking behavior), the difference is small and vice • Control The reduction of disease incidence, versa. For example, if preva- description can be found in epidemiology lence of STIs in a community is low (0. The aim of this study is of a specified disease in a defined geographical to obtain estimates of the burden of gynecologi- area as a result of deliberate efforts. For example, • Effective planning for health services. The agent of the disease may be avail- • To justify initiation of preventive measures. No dis- quality of life generated by healthcare interventions. It is the measure of the life-expectancy corrected 430 Epidemiology in Gynecological Diseases for loss of quality of that life caused by diseases and probability of an individual developing a change in disabilities. Some health interventions do not pro- health status over a fixed time interval. A year of normal health is given a QALY of 1 while death has a QALY of 0. Size of population at start of period Relative risk Disability-adjusted life years Relative risk (RR, also referred as rate ratio or risk DALYs are a measure of the burden of disease and ratio) compares the risk of developing a disease (any reflect the potential years of life lost due to pre- other health event, e. These disabilities can be physi- the risk in the exposed group by the risk in the cal or mental. One DALY can be thought of as one unexposed group The risk may be in the form lost year of ‘healthy’ life. The two groups are All these measures of disease burden are used to typically differentiated by demographic factors such measure the impact of disease burden in the com- as gender (e. Relative Risk of disease in exposed group MEASURES OF DISEASE ASSOCIATION risk = Risk of disease in comparison group AND IMPACT For the calculation of measures of disease associa- To measure a disease association means to quantify tion, two-by-two tables are very useful. If you are the relationship between exposure and disease interested in using them, please refer to books on among two groups. One probability is race, sex), biologic characteristics (immune status), that the event of interest will occur, the other prob- acquired characteristics (marital status), activities ability is that it will not occur. The measures of association des- in case–control studies, incidence of disease among cribed in the following section compare disease the exposed group is not calculated directly, occurrence among one group with disease occur- through the probability of developing disease rence in another group. A case–control study association include risk ratio (relative risk), odds estimates the proportion of cases with exposure and ratio and risk difference. In this chapter only rela- the proportion of controls with exposure in order tive risk and odds ratio will be discussed. Risk EFFECT OF A DISEASE ON AN INDIVIDUAL AND THE SOCIETY This is the probability that an event will occur, e. It is the that an exposure contributes to the frequency of 431 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS disease in the population. A measure of public husband may be needed to take over some health impact is used to place the association be- responsibilities that were initially been done by his tween an exposure and an outcome into a mean- wife. He will be overburdened, unable to concen- ingful public health context.

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J Fam Plann Appendicitis in pregnancy can be very hard to diag- Reprod Health Care 2011; 37: 231–40 nose since symptoms may be subtle and the cecum 4 discount 100mg extra super levitra with amex. Largest serous and appendix are displaced upwards in pregnancy order 100 mg extra super levitra otc. Torsion of ovarian cyst during pregnancy: a case report extra super levitra 100mg amex. Round ligament pain in a normal uterine Cases Journal 2009;2:9405 pregnancy Many pregnant women experience some pain dur- ing pregnancy due to the fact that the growing uterus puts traction on bands and ligaments. This is not a serious condition that needs treatment, but all serious complications (see Table 1) should be excluded. For women with no previous hyperemesis, a long interval between Nausea and vomiting of pregnancy has been a very births slightly increases the risk of hyperemesis in the common age-old phenomenon. So, relative impact of genetic and well understood, it occurs in almost 70% of preg- environmental factors and their possible interactions nant women. While ‘morning sickness’ remains 1 is also seen in hyperemesis. The traditional practice of giving the predispose women to the development of hyper- symptomatic antiemetic treatment without much 2 emesis. Low maternal age and multiparity inde- knowledge and confidence, has not changed over pendently increases the risk for nausea and vomiting the years. The severe end of the continuum, hyper- in pregnancy. Smoking before pregnancy and using emesis gravidarum, may complicate up to 0. Women working outside the home affected individuals progress from mild or moderate have a lower rate of nausea and vomiting than nausea and vomiting to hyperemesis gravidarum 4 housewives and women out of work. Hormonal which can be ‘complicated’ or ‘uncomplicated’, the factors are known to play an important role in the former referring to acetonuria, fluid electrolyte im- etiology. The cause seems to be associated with balance and Wernicke’s encephalopathy. Prematu- higher levels of selected forms of human chorionic rity, low birthweight, small for gestational age and gonadotropin (hCG) with the greatest thyroid- a 5-min Apgar score of <7, have been reported in stimulating capacity. Few isoforms of chorionic fetuses of mothers affected with hyperemesis gravi- gonadotropin act via the thyroid-stimulating hor- darum (level of evidence II–2), more so in women mone (TSH) receptor to accelerate iodine uptake. Also low prolactin levels and high estradiol levels are found to be associated with nausea in preg- ETIOLOGY 5 nancy. Researchers theorized that during human The cause of hyperemesis is still not well under- evolution, sickness during pregnancy protected the stood. The associated risk factors and the signifi- fetus by making the mother too nauseous to eat cance of these associations are depicted in Table 1. Support for this idea comes from the marily maternal and fetal factors that are not easily fact that many of the foods that tend to repulse modifiable, but their identification may be useful in pregnant women contain potentially harmful sub- determining those women at high risk for develop- stances. Also, women who have virtually no nausea ing hyperemesis and some might give clues on the or vomiting appear to be more likely to miscarry choice of treatment as in hyperthyroidism and dia- than those who experience some sickness. High risk for recurrence is observed in women logical and social factors influence this disease, such with hyperemesis in the first pregnancy. Young unwed mothers 40 Hyperemesis Gravidarum Table 1 Risk factors for hyperemesis gravidarum Numbers in Risk factor Significance Study design the study Prepregnancy underweight Increased risk (p< 0. Remark- elevated hCG causing a shift in pH along with able improvement with hospitalization is often pregnancy-induced gastrointestinal dysmotility and noted in such cases, with rapid relapse once released altered humoral as well as cell-mediated immunity to the home environment. Women with persona- in pregnancy are believed to be the reasons for lity disorders are predisposed to this condition. Lower socioeconomic status may also be an important risk factor of infection with RECENT DEVELOPMENTS H. Role of Helicobacter pylori Recently, an association between the bacterium Immunological factors Helicobacter pylori and hyperemesis gravidarum has been found as serologically positive H. Supporting this, agents troyed by the hyperactivated maternal immune active against H. The functional activation of natural killer and cytotoxic 41 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS T cells is found to be more prominent in hyper- such as peptic ulcer disease. The duration of vom- emesis than in women with an uncomplicated iting is important in assessing the risk of complica- pregnancy12. Thus hyperactivation of the maternal tions, like Wernicke’s encephalopathy as a result of immune system may be responsible for the onset of thiamine deficiency, which has been reported from hyperemesis, probably while maternal immune 3 weeks after the onset of symptoms17. Various hormonal and immunological factors Examination associated with hyperemesis are depicted in 5,6,9,13–16 Pulse rate and blood pressure along with assessment Table 2. Hyperemesis gravidarum is diagnosed when pro- tracted vomiting is present along with the inability Investigations to tolerate solid foods or fluids and the presence of ketonuria. Although nausea and vomiting are When available, electrolytes, liver function tests, very common symptoms of pregnancy, hyperem- thyroid function tests, creatinine, blood urea nitro- esis gravidarum is considered when all other causes gen, urinalysis mainly for ketonuria and a complete of persistent nausea and vomiting (as given in Table blood count including malaria are some of the 3) such as pyelonephritis, pancreatitis, cholecystitis, investigations that need consideration in the work- hepatitis, appendicitis, gastroenteritis, peptic ulcer up of severe hyperemesis gravidarum where starva- disease, thyrotoxicosis, malaria and hyperthyroid- tion and fluid imbalance can be encountered. Epigas- assessment can be done with clinical findings and tric pain and hematemesis should be specifically ketonuria (via dipstick method) whereas prolonged enquired about, which may be either an effect of symptoms need investigations such as electrolytes, prolonged vomiting (Mallory Weiss tear) or suggest liver and renal function tests, as well as thyroid other pathology which is causing the symptoms function tests. Investigations indicated for women Table 2 Factors associated with hyperemesis gravidarum Numbers in Association Significance Study design the study Low prolactin levels p< 0. Hyper- • Hepatitis emesis gravidarum symptoms that persist into the • Hydatidiform mole third trimester are associated with a higher inci- • Hyperparathyroidism dence of low-birth-weight infants24. Ketones readily • Pancreatitis • Peptic ulcer disease cross the placenta and may impair fetal neuro- psychological development25. Glucose metabolism is very active in pregnant woman due to the hypermetabolic state of pregnancy and the developing fetus’s energy needs and rapid tissue production. Thiamine defi- with hyperemesis are limited as the diagnosis is ciency can result in beri-beri symptoms that in- clinical, although the severity of disease may be clude fatigue, loss of appetite, emotional instability, indicated particularly by the electrolyte and liver sleep disturbances and abdominal discomfort. The cerebral pro- gression of thiamine deficiency resulting in Wernicke’s encephalopathy has been reported in Role of ultrasound 27,28 33 cases in the past 20 years. The initiation of Traditionally, twin and molar pregnancies have dextrose-containing intravenous fluids or aggres- been associated with women having hyperemesis sive nutrition support, without the provision of gravidarum3,18–20. However, a study found the same thiamine, can precipitate Wernicke’s encephalo- incidence of twin pregnancies in both groups with pathy. Thiamine administration of 100mg intra- or without excessive vomiting21. This study also venously (IV) or intramuscularly (IM) daily, or showed a lower miscarriage rate in women with enterally if tolerated, has been suggested for any hyperemesis gravidarum than controls consistent patient with more than 3–4 weeks of emesis29. Thus, a the greatest thyroid-stimulating capacity by acting clear association between twin and molar preg- via the TSH receptor to accelerate iodine uptake. Biochemical thyrotoxicosis is common in hyper- However, ultrasound may be done to relieve emesis gravidarum but the majority of women are maternal anxiety regarding her pregnancy viability clinically euthyroid. Response to therapy is thyroid drugs or beta-adrenergic blockers is only monitored daily by reduction in vomiting episodes, indicated if clinical and biochemical features of by the amount of fluid and food tolerated, increased hyperthyroidism are apparent. Hyperthyroidism is maternal weight, reduction in ketonuria and bal- often overdiagnosed and inappropriately treated in anced serum electrolytes. Therapy with intravenous fluids for correction Hyperemesis gravidarum can cause a mild in- of dehydration is the mainstay of management. The crease in liver enzymes (up to four times the upper volume of fluid should replenish the deficit along limit of normal) that return to normal when the with the loss through vomiting as well as meet nor- hyperemesis gravidarum is successfully treated32. Serum amylase may rise up to five times greater Fluid replacement is tailored to ketonuria or than normal, but this is usually salivary and not electrolytes and stopped once these are equalized pancreatic amylase33. Excessive retching during and a normal diet is resumed. In first 24 hours Psychosocial effects • 1l Lactated Ringer’s solution over 2h • 1l Lactated Ringer’s solution over 4h There has long been a presumption that women • 1l 0. It is likely that hyperemesis involves an interaction of biological, psychological and socio- MEDICAL THERAPIES cultural factors. There are good safety data to support the use of A recent study has devised ‘The Hyperemesis antihistamines, phenothiazines and metoclopra- Impact of Symptoms Questionnaire’ as a clinical mide in hyperemesis gravidarum. For an overview, tool to assess holistically the impact of the physical see Table 4. However, other causes of nausea and MANAGEMENT vomiting should be excluded before proceeding Hyperemesis gravidarum is in general a self-limiting with medicinal therapies. A few cohort and case–control studies with over Symptomatic treatment of nausea and vomiting, 170,000 exposures demonstrated pyridoxine and correction of dehydration and electrolyte imbal- doxylamine combination to be safe, in particular ance and prevention of complications of the disease relating to effects on the fetus42. Dehydrated and ketotic Corticosteroids are considered only as a last women require admission.

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